Haoran Li

Arpan Sasmal

Xinzhe Shi

Jean-François Soulé
email: jean-francois.soule@univ-rennes1.fr

Henri Doucet
email: henri.doucet@univ-rennes1.fr

Mr Mr H A Li

Mrs X Sasmal

Dr J.-F Shi

Dr H Soulé

Doucet

Halo-substituted benzenesulfonyls and benzenesulfinates: Convenient sources of arenes in metal-catalyzed C-C bond formation reactions for the straightforward access to halo-substituted arenes

Keywords: Benzenesulfonates, Benzenesulfinates, C-C bond formation, Catalysis

Palladium-catalyzed reactions using aryl halides as one of the coupling partners represent a very popular method for generating carbon-carbon bonds. However, such couplings suffer of important limitations. As most palladium catalysts are very effective for the cleavage of C-halo bonds (Halo = Cl, Br or I), in many cases, the presence of several halide functional groups on arenes is not tolerated. Since two decades, and especially during the last few years, a new class of coupling partners: benzenesulfonyl and benzenesulfinate derivatives has emerged as a powerful alternative to aryl halides for the Pd-catalyzed C-C bond formation, as the reactions performed with these substrates generally tolerate C-halo bonds. With these substrates, after a metal-catalyzed desulfitative coupling, a variety of halo-substituted arenes such as biaryls, styrenes, phenylacetylenes, acetophenones, benzonitriles… has been synthetized with high chemoselectivities. The use of these aryl sources allowed the synthesis of molecules containing several halo-substituents including iodo-substituents in only a few steps, and provides a very simple access to a very wide variety of halo-substituted arenes useful to material chemists and also to biochemists. In this review, we will summarize the scope of the use of halo-substituted benzenesulfonyls and benzenesulfinates as coupling partners in metal-catalyzed C-C bond formation.

The use of halo-substituted ArSO 2 R as aryl source in metal-catalyzed C-C bond formation reactions presents several advantages, as the reaction often proceeds without cleavage of the C-halo bonds, allowing the easy access to halo-substituted compounds.

Key words: Carbon-Halo bonds /

Chloro-, bromo-and also iodo-substituents on benzene derivatives are highly valuable as they can be very easily transformed into a huge number of other important functional groups via metalcatalyzed reactions or via more classical organic reactions. Moreover, halogen atoms may drastically modify the physical and biological properties of benzene derivatives. Therefore, the discovery of procedures allowing to prepare building blocks containing halo-substituents on benzenes currently represent a very important research area.

The arylation, vinylation, alkynylation, carbonylation or even cyanation of (hetero)aromatics via metal-catalyzed reactions provides a powerful access to a wide range of (hetero)aromatic derivatives. 1 For such reactions, palladium catalysis certainly represents the most widely used method. 2 However, it is well known that C-Cl, C-Br and especially C-I bonds are generally reactive in the presence of palladium complexes. 3 As a consequence, for Pd-catalyzed transformations, it is often not possible to employ halo-substituted benzene derivatives without cleavage of these C-halo bonds. In recent years, a new class of coupling partners: benzenesulfonyls and benzenesulfinates has been successfully employed to prepare functionalized benzene derivatives via Pd-catalyzed reactions. 4 A chief advantage of such coupling partners is that, the use of halo-substituted ArSO 2 R derivatives generally affords the functionalized benzene derivatives without cleavage of the Ar-Cl, Ar-Br or Ar-I bonds, allowing further transformations. Other advantages of these coupling partners is that many halo-substituted benzenesulfonyl chlorides are commercially available and that they are easy to handle. Moreover, ArSO 2 Cl derivatives can be easily prepared from sulfonic acids or sulfur substrates by chlorination; 5 and benzenesulfinates 6 or benzenesulfonyl hydrazides 7 can be obtained by the reduction of the corresponding ArSO 2 Cl. For these reasons, such aryl sources now provide new viable accesses to halo-containing benzene derivatives.

To the best of our knowledge, there is no review focusing on the metal-catalyzed functionalization of halo-substituted benzenesulfonyls and benzenesulfinates for access to halo-substituted arenes. 8 In this review, we will summarize the scope of the use of halo-substituted benzenesulfonyls and benzenesulfinates as coupling partners in Pd-and Rh-catalyzed C-C bond formation (Scheme 1). In the first section, the most general methods for the preparation of halo-substituted benzenesulfonyl chlorides, sodium benzenesulfinates and benzenesulfonyl hydrazides will be briefly described.

Then, in parts three to five, the Pd-catalyzed synthesis of halo-substituted biaryls via Stille, Suzuki-Miyaura and Hiyama shall be reviewed. Parts six and seven deals with the Pd-catalyzed reactions with aryl triflates, aryl or vinyl bromides and benzyl chlorides. The reactivity of (hetero)arenes for Pd-catalyzed desulfitative arylations via a C-H bond activation shall be presented in part eight.

Then, the reactions with alkenes and alkynes such as Heck and Sonogashira reactions will be described. Finally, the reactions of nitriles for carbonylation or cyanation of benzenes will be summarized. In the conclusion, the current challenges in the field will be evoked.

Access to halo-substituted benzenesulfonate and benzenesulfinate derivatives

The three major sources of halo-substituted benzenesulfonyl and benzenesulfinate derivatives for Pd-catalyzed reaction are benzenesulfonyl chlorides, sodium benzenesulfinates and benzenesulfonyl hydrazides.

There are a few methods for the preparation of halo-substituted benzenesulfonyl chlorides. In most cases, they are prepared by reaction of halobenzenes with chlorosulfonic acid or from sulfur substrates by (oxy)chlorination. 5 It should be mentioned that several halo-substituted benzenesulfonyl chloride derivatives, containing or not additional functional groups, are commercially available; and many of them can be purchased at an affordable cost (Figure 1). Even 2-and 4-iodobenzenesulfonyl chlorides are commercially available. Therefore, the use of halosubstituted benzenesulfonyl chlorides in cross-coupling reactions is very attractive. Conversely, relatively few halo-substituted benzenesulfinates are commercially available, and sodium 4-chlorobenzenesulfinate is one of the rare ones available at an affordable cost. However, benzenesulfinates can be easily prepared by reaction of benzenesulfonyl chlorides with a mixture of NaHCO 3 and Na 2 SO 3 . 6 Currently, there are no halo-substituted benzenesulfonyl hydrazides which are available at an affordable cost. These compounds are generally prepared by reaction of benzenesulfonyl chlorides with hydrazine (Scheme 2). Scheme 2. Synthesis of benzenesulfonyl hydrazides

Stille coupling

The rare examples of Stille couplings using halo-substituted benzenesulfonyl chlorides, without cleavage of the C-halo bonds, were described by Vogel et al. in 2003. They reported that the Pdcatalyzed reactions of 4-chloro-and 4-bromo-benzenesulfonyl chlorides with tributyl(phenyl)stannane derivatives afforded the biaryl derivatives 2 in moderate yields, but without cleavage of the C-Cl and C-Br bonds (Scheme 3, a). For these reactions Pd 2 (dba) 3 was associated to tri-2-furylphosphine as catalyst and 0.1 equiv. of CuBr were added to the reaction mixture. 9 One year later, they applied their procedure to the coupling of a tingalactal derivative with 4-chlorobenzenesulfonyl chloride (Scheme 3, b).

Suzuki coupling

Vogel et al. also reported the first examples of Suzuki couplings 11 using halo-substituted benzenesulfonyl chlorides (Scheme 4). 12 They employed 8-10 mol% Pd(PPh 3 ) 4 as catalyst and K 2 CO 3 as base. The coupling of nitro-or methyl-substituted arylboronic acids with 4chlorobenzenesulfonyl chloride gave the corresponding biaryls 4a and 4b in 62% and 65% yields, without C-Cl bond cleavage (Scheme 4, a). With 4-bromobenzenesulfonyl chloride, they performed successive Suzuki couplings. The first coupling reaction occurred with the sulfonyl chloride group and the second with the bromo substituent, affording terphenyl derivative 6 in 52% overall yield (Scheme 4, b). Conversely, the reaction of 4-iodobenzenesulfonyl chloride with 3 equiv. of p-tolylboronic acid directly afforded 4,4''-dimethylterphenyl derivative 7 in 52% yield as both iodo and sulfonyl chloride groups were reactive under these conditions (Scheme 4, c). bis-imidazole derivative and Pd(OAc) 2 . 13 They employed this complex in desulfitative Suzuki coupling. The reaction of with 4 equiv. of phenylboronic acid with chloro-substituted benzenesulfonyl chlorides in THF under reflux gave the corresponding biaryls 8 without cleavage of the C-Cl bonds (Scheme 5). Conversely, the reaction with 4-bromobenzenesulfonyl chloride, under the same reaction conditions, afforded terphenyl 9, as both Br and SO 2 Cl functional groups were reactive under these conditions. Scheme 5. Suzuki couplings with halo-substituted benzenesulfonyl chlorides using a polymersupported catalyst

The desulfitative Suzuki coupling is not limited to the use of benzenesulfonyl chlorides. The palladium-catalyzed desulfitative Suzuki reaction of sodium benzenesulfinates with a variety of arylboronic acids has been reported by Qi el al. in 2014 (Scheme 6). 14 The reaction, which was conducted under simple aerobic conditions, was tolerant to several functional groups on both coupling partners including chloro-and bromo-substituents, affording the corresponding biaryls 10 in good to excellent yields. These reactions were accelerated by the addition of a catalytic amount of Cu(TFA) 2 as co-catalyst. Scheme 6. Suzuki couplings using halo-substituted sodium benzenesulfinates

The Pd-catalyzed desulfitative and denitrogenative Suzuki coupling using halo-substituted benzenesulfonyl hydrazides has been reported by Dou et al. in 2015 (Scheme 7). 15 For these reactions, Pd(OAc) 2 /Xantphos (Xantphos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) was employed as the catalyst in the presence of K 2 CO 3 . Again, chloro-and bromo-substituents were tolerated on both coupling partners. Even 4-iodobenzenesulfonyl hydrazide was successfully employed, affording 4-iodo-1,1'-biphenyl 11c in 84% yield. Scheme 8. Suzuki couplings using aryltrifluoroborates

In summary, a few efficient procedures are now available for the preparation of halo-substituted biaryls using Suzuki type reaction. Qi's procedure in scheme 6 which is promoted by a phosphinefree catalyst and Wei's procedure (scheme 8, a) which employs an easily available catalyst and benzenesulfonyl chlorides as convenient aryl source are probably the most attractive.

Hiyama coupling

The first examples of Pd-catalyzed Hiyama-type cross-coupling 17 reactions using halo-substituted benzenesulfinates for the preparation of biaryls 14 were reported by Qi et al. in 2013 (Scheme 9, a). 18 The coupling of 2-or 4-chloro-and also 4-bromo-benzenesulfinates with phenyltriethoxysilane was achieved in good yields using 5 mol% PdCl 2 catalyst under aerobic conditions at 70 °C. The presence of fluoride in the reaction mixture was found to be essential, and tetrabutylammonium fluoride (TBAF) was shown to be the most efficient fluoride source for these cross-coupling reactions. One year later, Zhao et al. extended this reaction to 4-halo-substituted benzenesulfonyl chlorides (Scheme 9, b). 19 Again, TBAF was used as additive. Good yields in 15

were obtained from benzenesulfonyl chlorides and aryltri(methoxy)silanes bearing bromo-or chloro-substituents. 21 For these reactions, a mixture of Pd(OAc) 2 and Xphos (Xphos: 2dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) was used as catalyst and toluene as solvent. It should be mentioned that no base or additives were required for such couplings, and the reaction was performed under nitrogen. However, a poor yield in 17b was obtained for the reaction with sodium 4-bromobenzenesulfinate. One year later, they extended their procedure to the coupling of 2-bromobenzonitrile with sodium 4-chlorobenzenesulfinate. Again, the reaction was performed without base and additive, to afford the chloro-substituted biaryl derivative 17a in 80% yield (Scheme 11, a). 22 The same year, Forgione and Ortigies reported the coupling of the electron deficient aryl bromide, 4-bromobenzonitrile with sodium 4-chlorobenzenesulfinate (Scheme 11, b). 23 The corresponding 4-chlorobiaryl derivative 18 was isolated in 45% yield. For this reaction 1.5 equiv. of Cs 2 CO 3 was added to the reaction mixture. In 2013 again, Deng et al. reported the Pdcatalyzed desulfitative cross-coupling of sodium benzenesulfinates with benzyl chlorides (Scheme 11, c). 24 Chloro-substituents were tolerated on both coupling partners affording 1-chloro-4-(4methylbenzyl)benzene 19 in 66% yield. 25 The reaction occurred regioselectively at the 4-position of the 3,4-dibromofuranone derivative; whereas the C-Br bond at 3-position remained untouched. Sodium benzenesulfinates bearing ortho-and para-chloro substituents were tolerated, and the desired products 20 were obtained in 63-72% yields.

1

Homocoupling

The first examples of Pd-catalyzed homo-couplings of halo-substituted benzenesulfonyl chlorides were described by Miura et al. in 1990 (Scheme 14, a). 27 The best yields in 23 were obtained with 2.5 mol% PdCl 2 (PhCN) 2 catalyst, but good yields were also obtained with Pd(OAc) 2 . The reaction required the use of Ti(i-PrO) 4 as oxidant (2 equiv.), and tolerated chloro-and bromo-substituents on the benzenesulfonyl chloride. In 2005, Kashiwabara and Tanaka reported that the heating of benzenesulfonyl chlorides in the presence of 3 mol% Pd 2 (dba) 3 as the precatalyst and hexamethyldisilane also promoted desulfonylative homo-coupling (Scheme 14, b). 28 Under these conditions, from 4-bromobenzenesulfonyl chloride, 4,4'-dibromo-1,1'-biphenyl 24 was obtained in 74% yield. In 2015, Wu, Wang et al. reported the homo-coupling of halo-substituted benzenesulfonyl chlorides using a mixture of Pd(OAc) 2 and PPh 3 as catalyst (Scheme 14, c). 29 They performed the reaction with CuI, NaHCO 3 , Ag 2 CO 3 or Ag 2 O as oxidants and additives. With this procedure, para-meta-and also ortho-bromo-substituted benzenesulfonyl chlorides were successfully coupled affording products 25 in 65-96% yields. All the procedures reported in the scheme 14 required the presence of stoichiometric amounts of additives (Ti(i-PrO) 4 , hexamethyldisilane or CuI/Ag 2 CO 3 ). As Miura's procedure employs quite inexpensive Ti(i-PrO) 4

as additive and a phosphine-free catalyst, it appears to be the most convenient procedure for large scale synthesis of such biaryls from benzenesulfonyl chlorides. Scheme 14. Pd-catalyzed homo-couplings of halo-substituted benzenesulfonyl chlorides Then, in 2012, Luo et al. reported a more environment-friendly procedure which employs sodium benzenesulfinates as aryl source, water as the solvent, and a catalytic amount of Cu 2 O and molecular oxygen as clean terminal oxidant (Scheme 15, a). 30 The reaction tolerated 4-chloro-and 4-bromo-subtituents on the benzenesulfinate affording products 26 in good yields. Di-tertbutylperoxide can also be employed as oxidant for this reaction (Scheme 15, b). 31 Finally, halosubstituted benzenesulfonyl hydrazides have been homo-coupled by Zhao et al. affording biaryls 28 using Pd(OAc) 2 as the catalyst, DMA and THF as mixed solvent and Cu(OAc) 2 as oxidant (Scheme 15, c). Even 4-iodobenzenesulfonyl hydrazide has been employed, affording 28c in 84% yield without C-I bond cleavage. Scheme 15. Pd-catalyzed homo-couplings of sodium benzenesulfinates and benzenesulfonyl hydrazides

ClO 2 S PdCl 2(PhCN)2 2.5 mol% Ti( i-PrO)4 (2 equiv.) , m -xylene, 140 °C, 2 h R R R a) R' R' R' R Cl Br H Cl Cl R' H H Cl Cl Me Yield (%)

Direct desulfitative functionalization of C-H bonds

Transition metal-catalyzed direct arylations of (hetero)arenes through a C-H bond activation are certainly one of the most eco-friendly pathway to date for the preparation of (hetero)arylated arenes.

For such reactions, aryl halides were generally employed as aryl sources. 33 In recent years, benzenesulfonyl chlorides and sodium benzenesulfinates emerged as alternative aryl sources for Pdcatalyzed desulfitative couplings reactions with (hetero)arenes. In several cases, halo-substituted benzenesulfonyl chlorides and sodium benzenesulfinates have been successfully employed, especially for the arylation of 5-membered ring heteroaromatics. A few examples of couplings with benzene derivatives have also been reported.

Functionalization of six-membered ring arenes

Wang et al. reported in 2014 the direct desulfitative arylation of electron-deficient polyfluoroarenes using sodium benzenesulfinates as coupling partners (Scheme 16, a). 34a The best reaction conditions were 7 mol% PdCl 2 as catalyst in the presence of Ag 2 CO 3 as oxidant and Na as additive in wet DMF at 110 ºC as catalytic system. However, the arylated polyfluorobenzenes 30

were isolated in lower yields than under the Wang's conditions (Scheme 16, a). Moreover, this procedure requires the use of a large amount of the expensive phosphine ligand Xphos. Scheme 16. Desulfitative arylations of polyfluoroarenes Very recently, Kianmehr and Tanbakouchian described the Pd-catalyzed regioselective arylation of anilides using benzenesulfonyl chlorides as arylating agents and PdCl 2 as catalyst. (Scheme 17). 35 Their procedure provided regioselectively and in high yields the 2-aminobiaryl derivatives 31 containing chloro-or bromo-substituents. Scheme 17. Desulfitative arylations of anilides

Functionalization of five-membered ring heteroarenes containing one hetero-element

One of the advantages of the use of heteroarenes instead of arenes in metal-catalyzed C-H bond functionalizations is the strong electronic effect of the presence of the heteroelement on the ring, which allows to control more easily the regioselectivity. This part is divided in four points depending on the nature of the heteroatom on the ring (i.e., N with pyrroles, indoles and indolizines, S with (benzo)thiophenes, O with (benzo)furans, Se with selenophene).

Pyrroles, indoles and indolizines

The first Pd-catalyzed direct desulfitative arylation of indoles using a halo-substituted sodium benzenesulfinate was reported by Deng, Luo et al. in 2013 (Scheme 18). 36 This coupling reaction was performed with sodium 4-bromobenzenesulfinate as the coupling partner and a palladium(II) catalyst in the presence of 2 equiv. of CuCl 2 as oxidant in toluene/dioxane as solvent. With this coupling partner, the indole derivative was arylated exclusively at the C2-position providing products 32 in good yields.

Scheme 19. Desulfitative arylations of indoles with benzenesulfinic acids

In 2014, our group reported the arylation of pyrrole derivatives using halo-substituted benzenesulfonyl chlorides as coupling partners (Scheme 20). 38 The optimized conditions (i.e., 5 mol% of PdCl 2 (CH 3 CN) 2 in the presence of lithium carbonate in 1,4-dioxane at 140 ºC) allowed the formation of the C2-arylated pyrroles 34 in high yields and high regioselectivities. The reaction tolerated 4-chloro-, 2-, 3-or 4-bromo-and even 4-iodo-substituents on the benzenesulfonyl chloride and also halo-substituted thienylsulfonyl chlorides. 39 Poly(bromo)benzenesulfonyl chlorides were also successfully employed. 40 Two N-benzylpyrroles bearing bromo-substituents on the benzyl moiety were arylated at pyrrolyl C2-position by 3,5-dichlorobenzenesulfonylchloride to give 34u and 34v in high yields, without the cleavage of the C-Br and C-Cl bonds. 41 It should be mentioned that the coupling of 4-bromobenzenesulfonyl chloride with 1-methylpyrrole also proceeded in the "greener" solvents DEC and CPME or using neat conditions.

Scheme 22. Desulfitative arylations of indolizines with benzenesulfonyl chlorides

Then, in 2016, Zhao group extended the arylation of indolizines to halo-substituted sodium benzenesulfinates and benzenesulfonyl hydrazides (Scheme 23). 44 For the couplings of indolizines with sodium benzenesulfinates, tert-butylperoxyacetate was used as oxidant and Pd(OAc) 2 was associated to 2,2'-bipyridine as catalyst; whereas, for the reaction with benzenesulfonyl hydrazides, CuCl 2 was employed as oxidant and Pd(TFA) 2 as catalyst. Both catalytic systems afforded the C3arylated indolizines 40 and 41 in high yields. Moreover, the reaction tolerated bromo-and chlorosubstituents on the indolizine unit. However, as the sodium benzenesulfinates and benzenesulfonyl hydrazides have to be prepared, and as an oxidant is required for these two procedures, they are probably less attractive than the procedure of scheme 22. Our group also studied the desulfitative arylation of N-methylindole using 5 mol% PdCl 2 (CH 3 CN) 2 and Li 2 CO 3 in 1,4-dioxane at 140 °C as reaction conditions. 45 The coupling reaction with 4bromobenzenesulfonyl chloride was not regioselective, and a mixture of C2-and C3-arylated products 42 and 43 in 30:41 ratio was formed (Scheme 24, a). However, we demonstrated that an iodo-substituent at the indolyl C3-position act as temporary blocking group allowing the formation of halo-substituted 2-arylindoles 44 through direct desulfitative C2-arylation, followed by in situ deiodination (Scheme 24, b). 46 On the contrary, from 3-bromoindole derivatives, the 2-aryl-3bromoindoles 45 and 46 were obtained without debromination (Scheme 24, c). indole with benzenesulfonyl hydrazides (Scheme 25). 47 The reaction was conducted under oxygen atmosphere using Pd(OAc) 2 catalyst and 1.2 equiv. of trifluoromethanesulfonic acid as additive.

Halo-substituents were tolerated on both coupling partners.

Thiophenes and benzothiophenes

In 2014, our group reported the first Pd-catalyzed direct desulfitative arylations of thiophenes with benzenesulfonyl chlorides as coupling partners (Scheme 26). 40,48 Interestingly, the arylation took place exclusively at the thienyl C4-position. [108][109][110][111][112][113][114][115][116] 4-Chloro-, 4-bromo-, and even 4-iodobenzenesulfonyl chlorides in the presence of 5 mol% PdCl 2 (CH 3 CN) 2 and of 3 equiv. of lithium carbonate as base gave the C4-arylated thiophenes 48 in high yields. The reaction tolerated alkylor bromo-substituents at C2-position on thiophene and could be performed in 1,4-dioxane or CPME. 42 Reaction with 2-chloro-4-fluorobenzenesulfonyl chloride was also successful, affording the coupling product 48w in 78% yield. 49 Later, our group extended the reaction to 2-and 3bromobenzenesulfonyl chlorides. 39a,50 Using the same reaction conditions, 2-methylthiophene was coupled with 2-bromobenzenesulfonyl chloride to afford the C4-arylated thiophene 48f, without C-Br bond cleavage, in 76% yield. Thiophenes substituted at C2-position by pentyl, cyanomethyl or 4-methoxyphenyl groups in the presence of 2-bromobenzenesulfonyl chloride also gave the desired C4-arylated thiophenes 48g, 48h and 48r in 73-43% yields. 4-Trifluoromethyl-, 4-fluoro-, or 4,6difluoro-substituents on 2-bromobenzenesulfonyl chlorides were also tolerated. We also described a palladium-catalyzed one-pot "cascade" intermolecular C5-arylation using aryl bromides of some of these thiophene derivatives substituted at the C4-position by an aryl group containing an orthobromo substituent, followed by intramolecular arylation, which gives access to the corresponding phenanthro [9,10-b]thiophenes in a single operation. Scheme 26. Desulfitative arylations of thiophenes

Furans and benzofurans

From 2014, we applied our reaction conditions (see scheme 26) 48 to the synthesis of halosubstituted (benzo)furan derivatives 49 (Scheme 27). 40,51 n-Butylfuran or menthofuran were reacted with 4-chloro-, 4-bromo-and 4-iodo-benzenesulfonyl chlorides in the presence of 5 mol % PdCl 2 (CH 3 CN) 2 catalyst to afford the desired C2-arylated products 49a-49c, 49g and 49h in 50-76% yields. A similar yield in 49i was obtained for the coupling of 2-chloro-4fluorobenzenesulfonyl chloride with menthofuran. 49 Using the same reaction conditions, we also successfully arylated benzofuran at C2-position using 4-chloro-, 4-bromo-and also 3,5-dichlorobenzenesulfonyl chlorides as aryl sources. 39a,52 It should be mentioned that the reaction was completely regioselective, while reactions using aryl bromides as coupling partners, generally afforded mixtures of C2-and C3-arylated benzofuran derivatives. 53 Several arylations of (benzo)furans using the greener solvents DEC, CMPE or under neat conditions instead of 1,4dioxane have also been described. Scheme 27. Desulfitative arylations of (benzo)furans

Selenophenes

The first examples of Pd-catalyzed desulfitative arylations of selenophene have been reported by our group in 2017. 54 We examined the behavior of several (poly)halobenzenesulfonyl chlorides for coupling with this heteroarene using 10 mol% Pd(OAc) 2 catalyst and 3 equiv. of Li 2 CO 3 as the base in 1,4-dioxane. In all cases, the C3-arylated selenophenes 50 were regiospecifically produced (Scheme 28). Satisfactory yields in 50a-50e were obtained in the presence of benzenesulfonyl chlorides containing 2-, 3-, or 4-chloro-substituents and also 2-or 4-bromo-substituents. An additional ortho-ethyl-substituent on 4-bromobenzenesulfonyl chloride exhibited a minor influence, as a high yield of 74% in the target product 50o was obtained. 2-Bromobenzenesulfonyl chlorides bearing fluoro-or trifluoromethyl-substituents also afforded to the C3-arylated selenophenes 50j and 50l in high yields. The reactivity of two dibromobenzenesulfonyl chlorides was also examined.

In both cases, the target products 50k and 50p were obtained in good yields, without cleavage of both C-Br bonds. A bromo-substituent at C2-position on selenophene was also tolerated, affording the desired 4-aryl-2-bromoselenophenes, without cleavage of the selenophenyl C-Br bond.

Moreover, in the presence of 3,4-dibromobenzenesulfonyl chloride, the expected C4-arylated 2bromoselenophene derivative 50q was obtained without cleavage of the C-Br bonds on both coupling partners. Finally, we examined the reactivity of 4-iodobenzenesulfonyl chloride in the presence of selenophene and 2-bromoselenophene. The reaction afforded the β-arylated selenophenes 50f and 50g in low yields, but without cleavage of the C-I bond. Scheme 28. Desulfitative arylations of selenophenes

Functionalization of five-membered ring heteroarenes containing more than one heteroelement

Five-membered ring heteroarenes containing more than one hetero-element such as benzoxazoles, benzothiazoles and purines are important building blocks in pharmaceutical chemistry. Their modifications through Pd-catalyzed desulfitative direct arylations has also been reported in recent years. These arylations generally proceeded at their most acidic position, which is the C-H bond flanked by two hetero-elements. The C5-arylation of oxazole and triazole derivatives has also been described. Again benzenesulfonyl chlorides, benzenesulfinates, and benzenesulfonyl hydrazides were employed as the coupling partners, including those bearing halo-substituents, with high degrees of chemoselectivity.

Oxazoles and benzoxazoles

In 2011, Cheng et al. reported the first Pd-catalyzed desulfitative direct arylation of benzoxazole using halo-substituted benzenesulfonyl chlorides as coupling partners (Scheme 29, a). 55 For this reaction they employed 10 mol% Pd(OAc) 2 catalyst associated to 1 equiv. of CuI. The reaction displayed a broad substrate scope including 4-chloro-and 4-bromobenzenesulfonyl chlorides. The addition of a copper salt to the reaction mixture was found to be critical for the reactivity. ). 56b The reaction tolerated both chloro-and bromo-substituents on the benzenesulfinate and on the oxazole unit, affording products 55 in 64-85% yields. These two procedures provided higher yields of 2-arylbenzoxazoles than the reactions using benzenesulfonyl chlorides as aryl sources described in the scheme 29. a). 57 The reaction was performed using PdCl 2 (CH 3 CN) 2 associated to 1,10-phenantroline as catalyst in the presence of Na 2 CO 3 as base, with Cu(OAc) 2 and tetra-n-butylammonium bromide as additives in a mixture of dioxane/DMSO. The same year, Kwong et al. also described this transformation using a simpler catalytic system, namely, Pd(OAc) 2 associated to triphenylphosphine, in the presence of only Cu(OAc) 2 (2 equiv.) as additive, in dioxane under air atmosphere (Scheme 31, b). 58 They obtained slightly lower yields in 57 than Wan et al. Scheme 31. Desulfitative arylations of benzoxazoles

Benzothiazoles

In 2011, Deng et al. reported the Pd-catalyzed direct desulfitative C2-arylation of benzothiazole using a 4-chloro-and 4-bromo-substituted sodium benzenesulfinates as aryl sources (Scheme 32). 59 Again, a copper salt, which promotes the oxidation of Pd(0) into Pd(II), was added to the reaction mixture. 62 The desired desulfitative arylation products 61 were isolated in 79-81% yields using 5 mol% Pd(OAc) 2 as catalyst, and two equiv. of Cu(OAc) 2 as oxidant in dioxane/diglyme at 120 °C. It should be mentioned that the reaction occurred only at the C5-position of the thiazolyl unit. For this coupling, a Pd(0)/Pd(II) mechanism was proposed (Figure 3), where Pd(II) species A catalyzes the C-H bond activation process, followed by desulfitation to afford D and reductive elimination to afford the arylated product and Pd(0) species E, which was reoxidized into Pd(II) A by the copper salt. 65 However, the desulfitative Pd-catalyzed reactions with alkenes are not limited to Heck reactions. Reductive Heck type reactions, ring-opening of oxabenzonorbornadienes, alkylations followed by aryl migrations and desulfonylation for the synthesis of quaternary centers, and also the synthesis of 4-aryl-1,2,3,4-tetrahydroquinolines via multi steps reactions have also been reported.

Heck type reaction

The first example of Pd-catalyzed desulfitative Heck type reaction 64 using a halo-substituted benzenesulfonyl chloride was reported in 1989 by Miura et al. (Scheme 36). 65 They discovered that the reaction of 4-chlorobenzenesulfonyl chloride with n-butyl acrylate in the presence of 2.5 mol% PdCl 2 (PhCN) 2 under phase transfer conditions affords the corresponding (E)-3-(4chlorophenyl)acrylate in 89% yield, without C-Cl bond cleavage. One year later, they extended the reaction to 3-chlorobenzenesulfonyl chloride, 4-bromobenzenesulfonyl chloride and also to 4-chloronaphthalene-1-sulfonyl chloride. 66 A lower yield of 44% in 63c was obtained from the 4bromo-substituted benzenesulfonyl chloride. Scheme 36. Heck type reaction using halo-substituted benzenesulfonyl chlorides In 2016, our group extended this reaction to a wide variety of (poly)halo-substituted benzenesulfonyl chlorides (Scheme 37). 67 We observed that styrenes in the presence of bromo-or iodo-benzenesulfonyl chlorides and phosphine-free palladium catalyst PdCl 2 (MeCN) 2 led to the expected β-arylated Heck type products 65 and 66 with complete regio-and stereo-selectivities, without cleavage of the C-Br and C-I bonds. Moreover, the reaction tolerated a variety of substituents at C2-or C4-positions on the halobenzenesulfonyl chloride such as methoxy, ethyl, fluoro or trifluoromethyl. A bromo-substituent on the styrene derivative was also tolerated. From 4-bromobenzenesulfonyl chloride as central unit, the consecutive desulfitative Heck reaction followed by Pd-catalyzed direct arylation allowed to prepare heteroarylated stilbene derivatives in only two steps. Scheme 37. Heck type reaction using halo-substituted benzenesulfonyl chlorides Our group also investigated the reactivity of other alkenes under these reaction conditions (Scheme 38). The reaction of n-butylacrylate with 4-bromobenzenesulfonyl chloride afforded the corresponding cinnamate derivative 67b in 70% yield with complete regio-and stereo-selectivities in favor of the formation of the E-isomer. C2-substituents on 4-bromobenzenesulfonyl chloride, were tolerated affording the bromo-substituted cinnamates 67d and 67e in 83% and 85% yields.

Two dibromobenzene-1-sulfonyl chlorides were also successfully coupled with n-butylacrylate.

The reaction of n-butylacrylate with 4-iodobenzenesulfonyl chloride was also successful affording the Heck type product 67a in 82% yield, without C-I bond cleavage. Conversely, the reaction of 3,3-dimethylbut-1-ene with 4-bromobenzenesulfonyl chloride gave the styrene derivative 68a in only 36% yield, and from dimethyl(phenyl)(vinyl)silane and 4-iodobenzenesulfonyl chloride, the vinylation product 68b was also obtained in low yield. ClO 2 S PdCl 2(MeCN)2 5 mol% Li 2 CO 3 (3 equiv.), 1,4-dioxane, 100 ºC, 24 h 1.5 equiv. Scheme 38. Heck type reaction using halo-substituted benzenesulfonyl chlorides

n BuO 2 C R' R' R 4-I 4-Br 2-MeO 2-F 2-CF 3 2-Br 2-Br 3-Br 2-I R R R' H H 5-
In 2005, Dubbaka and Vogel described the use of a rhodium catalyst for the Heck reaction of 4bromobenzenesulfonyl chloride with styrenes (Scheme 39). 68 For this procedure, no base, phosphine ligand or additive were required and the (E)-1-bromo-4-styrylbenzene 69 was obtained in 70% yield. Chloro-substituents were tolerated on styrene, and a 2-phenylethene-1-sulfonyl chloride could also be employed as reaction partners. Scheme 40. Heck type reaction using halo-substituted sodium benzenesulfinates

The same year, Taniguchi employed 10 mol% PdCl 2 /2,2'-bis(2-oxazoline) as catalyst and a mixture of water, AcOH and DMF as the solvent with NH 4 PF 6 as additive to promote this coupling reaction (Scheme 41). 71 These reaction conditions afforded the 1,2-diphenylethenes 74 with an Econfiguration in good yields using 4-chlorobenzenesulfinate with styrene or benzenesulfinate with 4-chlorostyrene. Scheme 41. Heck type reaction using halo-substituted sodium benzenesulfinates

In 2012, Tian et al. described the use of halo-substituted benzenesulfonyl hydrazides for Heck type reaction with styrene derivatives (Scheme 42, a). 72 They reported that the treatment of chloro-and bromo-benzenesulfonyl hydrazides with styrene or 4-chlorostyrene using 10 mol% of Pd(OAc) 2 in DMSO/nitromethane under normal pressure of molecular oxygen as oxidant afforded the halo-substituted 1,2-diphenylethenes 75 in good yields with exclusive E selectivity. Recently, Yuen, So and Kwon employed Pd(OAc) 2 associated to a pyridine derivative as ligand and air as oxidant for such couplings (Scheme 42, b). 73 Again, the coupling products 76 were obtained in good yields. Scheme 42. Heck type reaction using halo-substituted benzenesulfonyl hydrazides

Wang and Miao investigated the Heck type reaction with benzenesulfinic acids (Scheme 43). 74 They employed Pd(OAc) 2 as catalyst and copper(II) acetate as oxidant. A set of benzenesulfinic acids including 4-chlorobenzenesulfinic acid were successfully coupled with 4-chlorostyrene affording products 77 in 67-83% yields. Moreover, under these conditions, the coupling of 4chlorobenzenesulfinic acid with an acrylate also provided the chloro-substituted Heck type product 78 in high yield. Scheme 43. Heck type reaction using halo-substituted benzenesulfinic acids Wu, Jiang et al. reported in 2015 the Pd-catalyzed desulfitative oxidative Heck-type reaction of sodium benzenesulfinates with allylic alcohols (Scheme 44). 75 They employed Pd(TFA) 2 associated to a phenanthroline ligand as catalyst and Cu(TFA) 2 as oxidant. This method provides a straightforward access to the halo-substituted β-aryl ketones 79 in moderate to good yields, as they demonstrated the compatibility of this reaction with iodo-and bromo-functionalities on the benzenesulfinate. 76 Their strategy was based on use of OAc as leaving group. The use of 10 mol% PdCl 2 (PPh 3 ) 2 catalyst, Li 2 CO 3 base in dioxane at 140 °C was found to be the optimal conditions. Two months later, Ma, Liu et al. described the same reaction using sodium benzenesulfinates as aryl sources (Scheme 45, b). 77 CuCl 2 was used as the oxidant and the reaction was performed under air atmosphere. 78 These reactions were performed with 5 mol% of Pd(OAc) 2 /2,2'-bipyridine as catalyst, in aqueous methanol in the presence of sulfuric acid at 90 °C. Only the conjugate addition products 82 were formed, as they never detected the Mizoroki-Heck type coupling product. They succeeded to identify reacting intermediates including an aryl Pd(II)-sulfinic species and a C=O-Pd complex, which were captured by ESI-MS/MS analysis. The same year, Deng et al. reported the conjugate addition of sodium benzenesulfinates with benzylideneacetone derivatives in 1,4-dioxane/H 2 O/TFA (2:2:1) by using Pd(OH) 2 as catalyst in the presence of DABCO (Scheme 46, b). 79 Bromo-and chloro-substituents were tolerated on both coupling partners, affording the halo-substituted 4,4diarylbutan-2-ones 83 in good yields. 80 They obtained the highly functionalized α-benzyl-β-ketoester derivatives 84 in good to excellent yields from chloro-and bromo-substituted benzenesulfinates. A bromo-substituent on the Baylis-Hillman adduct was also tolerated. The Pd-catalyzed reaction of halo-substituted benzenesulfonyl chlorides with enones was investigated by our group (Scheme 48). 81 The reaction with benzalacetone or β-ionone was found to afford selectively the conjugate addition products 85 and 86 instead of the expected Heck type products. The reaction tolerated chloro-, bromo-and even iodo-substituents on the benzenesulfonyl chloride.

1.5 equiv. Scheme 49. Pd-and Pt-catalyzed ring-opening of oxabenzonorbornadienes with sodium benzenesulfinates A mechanism for this Pd-catalyzed ring-opening reaction was proposed (Figure 5). In the first step, Pd(0) species A is generated from Pd(OAc) 2 through homo-coupling of sodium benzenesulfinates.

+

Then, the oxidative addition of oxabenzonorbornadiene to Pd(0) produces (π-allyl)-palladium(II) . 83 In the course of this reaction, two C(sp 2 )-C(sp 3 ) bonds were formed via the activation of C(sp 2 )-H bonds. The reaction proceeded using PdCl 2 catalyst, Li 2 CO 3 base and CuBr as additive, and tolerated chloro-and bromo-substituents on the benzenesulfonyl chloride and bromo-and iodo-substituents on the aniline derivative. 84 The reaction involved an oxidative Heck-type alkylation, an aryl migration, and a desulfonylation. A chloro-substituent on the benzenesulfonyl moiety was tolerated. 85 In the presence of 5 mol% Pd(OAc) 2 associated to 10 mol% 1,8-naphthalenediamine as catalytic system under argon, diphenylacetylene was hydroarylated to afford the corresponding trisubstituted alkenes 92 in good stereoselectivities and yields. 4-Bromo-and 4-chloro-benzenesulfinates were successfully employed, without cleavage of these C-halo bonds. Trifluoroacetic acid played an important role in this reaction, and its replacement by acetic acid decreased the reactions yields. . 86 This transformation was found to proceed under ligand-free conditions, and PdCl 2 was the optimal palladium source. The nature of the solvent exhibited a strong effect on this reaction and DMSO was found to be the best medium for such couplings. The reaction with 1ethynyl-4-methoxybenzene tolerated bromo-and chloro-substituents on the benzenenesulfinate. 87 A wide scope of terminal alkynes was reacted with 4-bromobenzenesulfonyl hydrazide using 5 mol% Pd(OAc) 2 /dppb as catalyst and Cu(OAc) 2 as oxidant, affording the bromo-substituted internal alkynes 94 in good to high yields. They also employed 2-and 3-bromobenzenesulfonyl hydrazides for coupling with a phenylacetylene derivative. Moreover, from 4-iodobenzenesulfonyl hydrazide and 1-ethynyl-4-bromobenzene, the corresponding dihalo-substituted 1,2-diphenylethyne 94k was obtained in 48% yield. In all cases, only the coupling reaction involving the sulfonylhydrazide functional groups occurred. Finally, they prepared more complex molecules from some of the prepared halo-substituted 1,2-diphenylethynes through Suzuki, Sonogashira and Heck reactions. 88 For these reactions, a combination of Pd(OH) 2 and 1,10-phenanthroline was used as catalyst. They observed that the reaction of sodium 4bromobenzenesulfinate with 4-methylbenzonitrile in 1,4-dioxane/water (3:2) in the presence of trifluoroacetic acid in air gave the bromo-substituted benzophenone derivative 95 in 50% yield.

Under the same conditions, a 4-chloro-substituted benzonitrile reacted with sodium ptoluenesulfinate to give the corresponding chloro-substituted benzophenone 96 in 73% yield. Then, Miao and Wang extended the reaction to benzenesulfinic acids (Scheme 55, b). 89 The reaction of benzonitriles and benzenesulfinic acids was promoted by Pd(OAc) 2 /2,2'-bipyridine catalyst and concentrated H 2 SO 4 in isobutyl alcohol to afford the halo-substituted benzophenones 97 via hydrolysis of the ketimine intermediates. The reaction tolerated bromo-and chloro-substituents on the benzonitrile moiety and chloro-substituents on the benzenesulfinic acid. Moreover, they obtained higher yields than those reported by Li and Deng (Scheme 55a). Scheme 55. Pd-catalyzed addition of sodium benzenesulfinates to nitriles In 2011, Lahred et al. reported a Pd-catalyzed microwave-promoted procedure to synthesize aryl ketones and from benzenesulfinates and nitriles (Scheme 56). 90,91 Pd(O 2 CCF 3 ) 2 , which was found to be more efficient than Pd(O 2 CCH 3 ) 2 as Pd-source, was associated to 6-methyl-2,2'-bipyridyl ligand.

They evaluated the scope of the reaction by employing a set of sodium 4chlorobenzenesulfinates to react with acetonitrile under their optimized conditions. They also employed a wide variety of halo-substituted benzonitriles. 2-, 3-, And also 4-bromo-substituents on benzonitriles were tolerated affording the bromo-substituted benzophenone derivatives 98 and 99 in good yields. 92 This reaction tolerated bromo-and chlorosubstituents on the benzensulfonyl chlorides. After screening of several catalysts, copper sources and bases, they found that the use of PdCl 2 (MeCN) 2 associated to Cu(acac) 2 and Na 2 CO 3 furnished the halo-substituted benzonitriles 100 in good yields. 93 The use of Pd(OAc) 2 and 2,2′-bipyridine as the catalytic system with p-nitrobenzenesulfonic acid as additive using a mixture of 2-MeTHF and water as solvent afforded the 2-arylbenzofurans 101 in moderate to excellent yields. The reaction tolerated chloro-substituents on the sodium benzenesulfinate and bromo-and chloro-substituents on the 2-hydroxyarylacetonitrile unit. This reaction might proceed via the formation of a ketimine, which undergoes hydrolysis to form the corresponding 2-(2hydroxyphenyl)-1-arylethanones under acidic conditions. Then, an intramolecular annulation under acidic conditions would deliver the 2-arylbenzofurans. In summary, during the last decade, the scope of the Pd-catalyzed formation of C-C bonds using halo-substituted benzenesulfonyl and benzenesulfinate derivatives such as ArSO 2 Cl, ArSO 2 Na and ArSO 2 NHNH 2 has been largely extended. The use of halo-substituted ArSO 2 R as coupling partners presents several advantages compared to the reactions with aryl halides, as in most cases, the reaction proceeds without cleavage of the C-halo bonds, even in the presence of iodo-substituted arenes. The numerous transformations which have been recently reported using these coupling partners demonstrate that they are actually regarded as some of the most promising building blocks for the access to halo-substituted compounds. Moreover, in some cases, such as for the Pdcatalyzed direct arylations of thiophenes or selenophenes, C3-arylation products were obtained; whereas, with aryl halides regioselective C2-arylated heteroaromatics were generally produced. A modification in the regioselectivity was also observed for the arylation of benzofurans, as ArSO 2 Cl selectively afforded the C2-arylated benzofurans; whereas, reactions performed with aryl halides led to mixtures of mono-and di-arylated benzofurans. Despite the numerous recent reports on the reactivity of benzenesulfonyls and benzenesulfinates as substrates in Pd-catalyzed reactions, a number of challenges remain. As benzenesulfonyls chlorides are much more easily available than benzenesulfinates and sulfonylhydrazides, the extension of some of the reactions reported here to these aryl sources is important. In several cases, the substrate scope was very limited and/or quite high catalyst loadings were employed; therefore, more efficient catalysts permitting wider substrate scope and/or lower catalyst loadings need to be discovered in order to provide more attractive procedures. Concerning catalytic cycles and elementary steps, for most of the transformation reported using ArSO 2 R derivatives, a large number of interrogations are not addressed. In the presence of benzenesulfonyl chloride, the first step might be the oxidative addition of ArSO 2 Cl to a Pd(II) species and release of SO 2 to afford a Pd(IV) intermediate, although a Pd(0)/Pd(II) mechanism is also possible. Determining in more detail the reasons of the much higher reactivity of the SO 2 R group vs the halo-substituents of arenes for these reactions could allow further improvement in terms of reactions selectivities and yields, substrate scope and catalyst efficiency.

However, undoubtedly the use of ArSO 2 R derivatives as substrates for metal-catalyzed coupling reactions will help both material and synthetic chemists a great deal making the access to many important halo-substituted arene derivatives simpler.

(1) L. Ackermann, Modern arylation methods; Wiley, 2009.

  with aryl triflates and aryl, benzyl or vinyl halides 7. Homocoupling 8. Direct desulfitative functionalization of C-H bonds 8.1 Functionalization of six-membered ring arenes 8.2 Functionalization of five-membered ring heteroarenes containing one hetero-

  Scheme 1.

Figure 1 .

 1 Figure 1. Selection of commercially available halo-substituted arenesulfonyl chlorides

Scheme 3 .

 3 Scheme 3. Stille coupling using halo-substituted benzenesulfonyl chlorides

  Scheme 4. Suzuki couplings using halo-substituted benzenesulfonyl chlorides

Figure 2 .

 2 Figure 2. Proposed catalytic cycle

Scheme 24 .

 24 Scheme 24. Desulfitative arylations of indoles

Scheme 25 .

 25 Scheme 25. Desulfitative arylations of indoles

RScheme 29 .

 29 Scheme 29. Desulfitative arylations of oxazoles and benzoxazoles

  Scheme 32. Desulfitative arylations of benzothiazole

  Scheme 34. Desulfitative arylation of a thiazolotriazole

  Figure 3. Proposed mechanism

Scheme 44 .

 44 Scheme 44. Heck-type reaction of sodium benzenesulfinates with allylic alcohols

Scheme 45 .

 45 Scheme 45. Heck coupling of benzenesulfonyl chlorides with glycals

Scheme 46 .

 46 Scheme 46. Pd-catalyzed desulfitative conjugate additions

  Figure 5. Proposed mechanism

Scheme 50 .Figure 6 .

 506 Scheme 50. Pd-catalyzed cascade reaction of N-allyl-N-arylsulfonamides with benzenesulfonyl

Scheme 51 .

 51 Scheme 51. Pd-catalyzed alkylation/aryl migration/desulfonylation

Scheme 52 .

 52 Scheme 52. Pd-catalyzed desulfitative hydroarylation of an alkyne

Scheme 53 .

 53 Scheme 53. Pd-catalyzed Sonogashira cross-couplings of sodium 4-halobenzenenesulfinates

Scheme 57 .

 57 Scheme 57. Pd-catalyzed desulfitative cyanation of benzenesulfonyl chlorides

Scheme 58 .

 58 Scheme 58. Pd-catalyzed tandem reaction of 2-hydroxyarylacetonitriles with sodium

. Coupling with aryl triflates and aryl, benzyl or vinyl halides

	Scheme 10. Hiyama-type cross-coupling reactions with benzenesulfonyl hydrazides
	PdCl 2 5 mol% 6Aryl triflates and aryl, benzyl or vinyl halides can also be employed as coupling partners in Pd-Si(OEt)3 1.2 equiv. R a) 14
	+ catalyzed desulfitative cross-couplings. In 2012, Li, Duan et al. reported a procedure for the 86 4-Br R 14c NaO 2 S Bu 4 NF (1 M in THF), 70 °C, 3 h, air R Yield (%) 80 84 2-Cl 4-Cl 14a 14b
	equiv. coupling of aryl triflates with sodium benzenesulfinates containing 4-chloro-or 4-bromo-
	b)
	Si(OMe)3 substituents (Scheme 11, a). R	R		R'
	+ 1 equiv. ClO 2 S	R'	Pd 2(dba)3 3 mol% Bu 4 NF . 3H 2 O (1 equiv.), DMF/MeCN 1:4, 100 °C, 3 h	R H H Cl	R' Cl Br H	15 15a 15b 15c	Yield (%) 86 79 89
	1 equiv.					Br	H	15d	83
	Scheme 9. Hiyama-type cross-coupling reactions
	The Pd-catalyzed Hiyama coupling reaction using benzenesulfonyl hydrazides as coupling partners
	was reported by Zhou et al. in 2015 (Scheme 10, c). 20 They performed this reaction with Pd(TFA) 2
	as	catalyst,	1,3-dimethyl-2-imidazolidinone	as	solvent	and
	tetrabutylammoniumdifluorotriphenylsilicate (TBAT) as additive under oxygen. This reaction
	tolerated 4-chloro-, 4-bromo-and even 4-iodo-substituents on the benzenesulfonyl hydrazide.
	Again, high yields in the desired halo-substituted biphenyls 16 were obtained. However due to the
	high molecular mass and cost of TBAT, this procedure appears to be less attractive than the Qi's
	procedure (Scheme 9, a).
	R	Si(OMe)3			R			R'
	1.2 equiv.	Pd(TFA)2 5 mol%			16
	+ H 2 NHNO 2 S		TBAT (2 equiv.), DMI, 60 °C, 12 h, O 2 R'	R H H H	R' Cl Br I	16a 16b 16c	Yield (%) 92 87 90
	1 equiv.				Cl	H	16d	90
	DMI: 1,3-dimethyl-2-imidazolidinone TBAT: tetrabutylammoniumdifluorotriphenylsilicate

  32

	NaO 2 S a)	R	PdCl 2 2.5 mol%, Cu 2 O 20 mol% O 2, H 2O, 100 °C, 24-30 h	R	R Cl		R Yield (%) 26 81 26a
	b)				Br		26b	77
	NaO 2 S	R	Pd(OAc)2 1 mol%	R			R
	c)	di-tert -butylperoxide (1 equiv.) , MeCN, 60 °C, 12 h, air		R Cl Br	27 Yield (%) 87 85 27a 27b
	H 2 NHNO 2 S	R	Pd(OAc)2 3 mol%
			Cu(OAc)2 (1 equiv.) , DMA/THF 1:1, 80 °C, 3 h
			R				R
							28
				R Cl	28a	Yield (%) 90
				Br	28b	88
				I		28c	84

  3 PO 4 •H 2 O as base in wet DMSO. The reaction was found to tolerate both 4-bromo and 4-choro-substituents on the sodium benzenesulfinate affording products 29 in 75-82% yields. The same reaction, using 4-chloro-substituted sodium benzenesulfinate as aryl source, was reported by Weng and co-workers (Scheme 16, b). 34b They employed 20 mol% [PdCl(allyl)] 2 associated to 20 mol% of Xphos (Xphos: 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl) in the presence of 2 equiv. of Ag 2 O

  Scheme 18. Desulfitative arylations of indoles with sodium benzenesulfinates Free (NH)-indoles were arylated with benzenesulfinic acids by Wang et al., via a Pd-catalyzed desulfitative coupling reaction, in the presence of AgOAc as oxidant and sulfuric acid as additive using microwave heating affording 33 in 56-80% yields (Scheme 19).37 The use of H 2 SO 4 as additive might minimize the decomposition of indoles and favor the regioselective functionalization at indole C2-position. The benzenesulfinic acids scope included 2-chloro-, 4-chloro-and also 4bromo-substituents. In addition, the reaction tolerated bromo-substituents on the indole.

	R	H N 1.4 equiv. +	R'	PdCl 2 5 mol% AgOAc (2 equiv.), H 2 SO 4 (98%, 2 equiv.), DMF/CH 3 CN 1:1, MW, 100 ºC, 40 min	R R H H	R' 4-Cl 4-Br	Yield (%) 80 72 R' 33 33b H N 33a
	HO 2 S				H	2-Cl	33c	56
						Cl	H	33d	71
						Br	H	33e	66
			N		Pd(COD)Cl2 5 mol%				N
	R NaO 2 S	+		CuCl 2 . 2H 2 O (2 equiv.), toluene/dioxane 1:1, 110 ºC, 24 h R'	R	R H Br	R' Br Me	32 32a 32b	Yield (%) 81 78 R'
		2 equiv.

  Several examples of desulfitative Heck type reactions 64 have been reported since the seminal work reported byMiura et al. in 1989.

					N N	N +	R'
		N N	N + O -	Pd(OAc)2 5 mol%, 1,10-phenanthroline 40 mol%	Cl	O -62
	NaO 2 S Cl	+		Ag2 CO 3 (1 equiv.), K 3 PO 4 (2 equiv.), DME/DMF 3:7, 80 ºC, 12 h, air R'	R' Br tBu F H	62a 62b 62c 62d	Yield (%) 75 82 75 82
	1.2 equiv.		MeO Me	62e 62f	93 87
	Scheme 35. Desulfitative arylations of a triazole N-oxide
	9. Reaction with alkenes

  Scheme 49, b).82b The ring-opening products 88 were produced in slightly lower yields than with the palladium catalyst.

	ClO 2 S 1 equiv. O a) 1.5 equiv. + OH ClO 2 S 1 equiv. O b) + NaO 2 S 1 equiv. O R 1.5 equiv. + NaO 2 S 1 equiv. O R Yield (%) PdCl 2(MeCN)2 5 mol% Li 2 CO 3 (3 equiv.), 1,4-dioxane, 140 ºC, 24 h Br R R' Br OH PdCl 2(MeCN)2 5 mol% Li 2 CO 3 (3 equiv.), 1,4-dioxane, 140 ºC, 24 h Pt(COD)Cl2 5 mol%, PPh 3 10 mol% AgSbF6 (0.03 equiv.), MeOH, 70 ºC, 15 h R' Pd(OAc)2 5 mol%, PCy3 10 mol% DCE/H 2 O 5:1, 65 ºC, 2 h, air R' Yield (%) R 4-Cl 4-Br 4-I 2-Br O Cl 86b 86c 86d O 86a OMe Yield (%) 77 65 67 78 85 68% R 86 OH OH R R' 4-Cl 4-Br 3-Cl OH OMe OMe 93 75 R' Cl Br OH Br Br R' 96 69 98 R' 4-Cl 4-Br 3-Cl OH R' OH R a) b) 87 88 87a 87b 87c 87e 87f 87g 87h 87i catalyst to promote this reaction (3 equiv. 2-Cl 93 2-Cl 87d 87j	Br Yield (%) R' R' 88 57 98 R' R' 92
	OMe Scheme 48. Pd-catalyzed desulfitative conjugate additions with benzenesulfonyl chlorides Br Yield (%) 80 R' 4-Cl R' 88e 85% Yield (%) 87 4-Cl 88a 88f
	4-Br	88b	62	4-Br	88g	40
	3-Cl	88c	90	3-Cl	88h	92
	9.3 Ring-opening of oxabenzonorbornadienes 2-Cl 83 2-Cl 88d	88i	88
	Yang et al. described in 2016 the Pd-catalyzed syn-stereocontrolled ring-opening reaction of
	oxabenzonorbornadienes with sodium benzenesulfinates for the preparation of cis-2-aryl-1,2-
	dihydronaphthalen-1-ols 87 (Scheme 49, a). 82a The reaction tolerated several functional groups
	including bromo-and chloro-substituents on the benzenesulfinate and bromo-substituents on the
	oxabenzonorbornadiene. In 2017, this group employed a platinum catalyst instead of a palladium

11. Reaction with nitriles 11.1 Carbonylation In

  2011, Li, Deng et al. reported the synthesis of aryl ketones via Pd-catalyzed addition of sodium benzenesulfinates to nitriles (Scheme 55, a).

	+ H 2 NHNO 2 S R 1.2 equiv. H	R' Cu(OAc)2 . H 2 O (2.4 equiv.), Pd(OAc)2 5 mol%, dppp 5 mol% DMF, 100 ºC, 0.5 h	R	94	R'
	1 equiv.
					Ph
					O
	HO			Br			Br
		94a 67%				94l 51%
	R''			R'	N	94m 60%	Br
	R'' CN Br n-Pr	R' 4-Br 4-Br 3-Br	94b 94c 94d	Yield (%) 62 80 72			94n 56%	Br
	n-Pr	2-Br	94e	34
	Br	H	94f	75
	Br Br	4-OMe 4-F	94g 94h	57 85			Br
	Br Br Br	4-Cl 4-NO 2 4-I	94i 94j 94k	81 92 48			94o 86%
	Scheme 54. Pd-catalyzed Sonogashira cross-couplings of benzenesulfonyl hydrazides

  In 2012, Cheng et al. developed a Pd-catalyzed desulfitative cyanation of benzenesulfonyl chlorides, affording benzonitriles (Scheme 57).

					O
						Cl
					R	98
	RCN 1.5 equiv.	Pd(O2 CCF 3)2 8 mol%, 6-methyl-2,2'-bipyridine 12 mol%	R Me Et CH 2 Ph	98a 98b 98c	Yield (%) 79* 73* 66*
	NaO 2 S	+	R' THF/H 2 O 1:1, MW 100 ºC, CF 3 CO 2 H (10 equiv.), 1 h	O	R'
	1 equiv.		R''		99
				R'' 4-Br	R' Me	99a	Yield (%) 68
				4-Br	H	99b	61
				4-Br	MeO	99c	62
				4-Br	Cl	99d	51
				H	Cl	99e	77*
				4-Cl	Me	99f	62
				2-Br	Me	99g	70
				3-Br	Me	99h	67
				4-CHO	Cl	99i	53
			*: RCN 5 equiv. .	2-Br 3-Br	Cl Cl	99j 99k	89 54
	Scheme 56. Pd-catalyzed addition of sodium benzenesulfinates to nitriles
	11.2 Cyanation

Acknowledgements

We thank China Scholarship Council for providing financial support to H. L.; CEFIPRA for providing financial support to A. S.; and ANR for providing financial support to X. S.

Bibliographical sketch

Haoran Li was born in P.R. China. He joined the international master's program "Catalysis, Molecules and Green Chemistry" in the University of Rennes 1 (France) in 2015. He performed his master's research training in Prof. C. Darcel's team in the University of Rennes 1. He currently works towards a PhD degree of ENSCR under the supervision of Dr. Henri Doucet. He received a grant from the China Scholarship Council (CSC) in 2017. His work focuses on the C-H bond functionalization using palladium catalysis. Arpan Sasmal received his B.Sc degree in Chemistry from University of Calcutta in 2014. He received his M.Sc degree in Chemistry from IIT Madras in 2016. Afterwards, he did International Master in Molecular Catalysis and Green Chemistry from University of Rennes 1 (France) in 2017. Now he is a PhD student at University of Rennes 1 (France) under the supervision of Prof. Henri Doucet and Dr. Jean Francois Soule. His research focuses on C-H bond activation using palladium catalysis.

Scheme 39. Heck type reaction using halo-substituted benzenesulfonyl chlorides Several groups extended the desulfitative Heck reaction to other aryl sources: sodium 4bromobenzenesulfinate (Schemes 40 and 41), benzenesulfonyl hydrazides (Scheme 42) and benzenesulfinic acids (Scheme 43). The major drawback of these procedures is that these three aryl sources are less easily available than benzenesulfonyl chlorides. Moreover, the presence of an oxidant is required. Therefore, they are probably less attractive than the procedures described in the schemes 36-39.

In 2011, Deng et al. described the reaction of an acrylate with sodium 4-bromobenzenesulfinate (Scheme 40, a). 69 They observed that both the ligand and the solvent played an important role in


Dominique Boutet
email: dboutet@noos.fr

Gesturing, as Substratum and Support: a Case of Continuity

Keywords: Gesture, Articular description, Proprioception

Gesturing can be understood through the substratum which simultaneously produces and reveals it. Up until now, most research has been motivated by the case where the body reveals gesturing. A study of the means of producing gestures makes it possible to identify the formal criteria that distinguish types of gestures. Our choice is made on the basis of articular description, where the relationship between differing degrees of liberty is described. There exist dynamic relationships that trace a topological geometry.

A morphogenetic description centred on form follows them in their movements. The interest of this physiological approach also resides in the contours traced by each gesture. Articular constraints create structural and dynamic links between given degrees of freedom. Gestural schemas are freed and at times develop their continuity over several segments by positing a relation that assumes the same value as the original form.

An inventory of these variations shows how the upper member functions both as a substratum that structures gestural forms and as an anamorphotical support for the morphological variations of each gesture. We will show how segmental organising centres structure and project gestural units. We will present specific gestures which are distinguished solely by the flux in their propagation of movement.

Introduction

The means of producing gestures seem to have been overlooked in the analysis of phenomena involved in symbolic gesturing. It seems that the body has been considered as a place where things happen, and where gestures appear without any physical means of support. In its place, there seems to be just a kind of support without any real substance. The body is akin to a disjointed puppet, whose real substratum is situated on the cognitive level, and which projects on vision, in fact, its own specular image.

The upper members constitutes the subject of this article. The description of articulations, as well as of their geometrical relationships and phenomena of coalescence give a bit of substance to the body and to the production of gestures. The transfers of intra-or intersegmental movement and the schemas that issue from them are structured into a number of emergent units. Each gestural unit presents multiple formal envelopes, either discontinuous or scattered for a given visual mode. On the other hand, the gestural unit presents a single formal envelope, continuous for the proprioceptive mode. This is evidence that the body can structure gestural units.

The Necessity for a reference system

In gesturing, the necessity for a frame of reference implies the obligation to have a reference system. This system consists of a reference point having least one point of view [START_REF] Tversky | Langage et perspective spatiale[END_REF] and one or several indices capable of describing, at each moment, both the positions and movements of all body segments (fingers, hand, forearm, arm and shoulder). Since antiquity, [START_REF] Cicero | La Nature des dieux[END_REF][START_REF] Quintilian | Livre XI. Institution oratoire[END_REF][START_REF] Vitruvius | Les Dix Livres de l'architecture[END_REF][START_REF] Darwin | L'expression des émotions chez l'homme et les animaux[END_REF] and up until recently [START_REF] Merleau-Ponty | Phénoménologie de la perception[END_REF]MacNeill, 1992;[START_REF] Martin-Dupont | Les Modalités d'évaluation objective dans le domaine de la communication non verbale[END_REF][START_REF] Calbris | L'expression gestuelle de la pensée d'un homme politique[END_REF] it has been commonly accepted to adopt an egocentric, tridimensional reference point, whether axial or polar.

Articulatory systems of reference

We shall focus our study on an allocentred reference point: the physiological notation of articulatory movements. This notation takes as its basic unit the degree of freedom (e.g. flexion/extension of the hand). All degrees of freedom define a direction of movement according to two opposed senses (i.e. flexion and extension); they are all characterised by an axis of rotation located at the level of a joint (articulation) (e.g. the axis crossing the width of the wrist), and at times at the level of two articulations. A segment turns and is systematically defined by an amplitude (for manual flexion/extension, a total amplitude of 170°, or 85° for flexion and 85° for extension) around each of these axes [START_REF] Kapandji | Physiologie articulaire[END_REF].

The degrees of liberty

From the fingers to the shoulder (with the exception of the shoulder itself), there are 28 degrees of freedom. This means that we have a system and a space composed of 28 dimensions, thus forming a complex that develops its combinations in a range covering the three spatial dimensions plus a fourth: time or R4. This range is analogous to a motion picture screen, neither more or less1.

The fingers

Each finger comprises 4 degrees of freedom (1 movement of flexion/extension per digit, or 3 degrees, plus 1 movement of abduction/adduction allowing the lateral movement of each finger). The thumb has 5 degrees of freedom, which renders its mobility yet more complex.

The hand

The hand moves along 3 axes of rotation which define 3 degrees of freedom. A rotational axis that runs across the width of the wrist defines a movement of flexion (bringing the palm of the hand towards the internal surface of the forearm, 85°), on the one hand, and extension on the other (in the opposite direction, 85°).

Another rotational axis bisects the preceding one perpendicularly by crossing the wrist at the base of the hand in a front-to-back direction2 (the flat of the palm versus the back of the hand). It introduces a degree of freedom called abduction/adduction. The amplitude of this degree of freedom is 45° for adduction (movement on the side of the little finger) and 15° for abduction (movement on the side of the index finger), for a total amplitude of 60°.

Finally, the last degree of freedom concerns what is commonly called the rotation of the hand. The rotational axis of this movement runs along the forearm and brings two articulatory centres into play (wrist and elbow). The movement being easily seen in the hand, it is generally attributed to it alone. Starting from a position of reference -fingers pointing forward, the thumb turned upwards -the hand turns relative to two poles called pronation (the palm turned downwards in the aforementioned position of reference up to 85°) and supination (the rotation of the hand is effected in the opposite sense, with the palm turned upwards relative to the initial position, up to a maximal amplitude of 85°).

The forearm

The forearm has two degrees of freedom: flexion/extension and interior/exterior rotation. The first dimension is measured against a position de reference in which the forearm is in line with the arm at the side of the body, the palm open and facing front. For this position the extension is equal to 0 and the forearm can be folded back on the arm by a flexional movement up to 145°. It can be seen that movements of extension are always measured relative to a previous position of flexion.

Interior/exterior rotation is effected relative to an axis which follows the humerus, the articulatory point being situated on the shoulder. However, its effect actually concerns the forearm; and so it is borne by this segment. In order to render this movement both visible and distinct from the relative rotation of pronation-supination, the forearm must be flexed at 90°, the arm lying alongside of the body. The intermediate position (neither interior nor exterior) places the hand on a sagittal plane, i.e., the fingers pointing forward. Thus located, the internal surface of the forearm is brought up to the abdomen for an interior rotation of about 80° in amplitude and this segment moves to the exterior so as to turn its internal surface to the front in a nearly frontal plane, for an amplitude of about 90°.

The arm

The last segment is the arm, which has 3 degrees of freedom. The range of flexion/extension is made possible by an axis of rotation that passes through the shoulder frontally (in a sense, from one shoulder to the other). During flexion, it carries the arm forward, then upward (180° range) up to a vertical position opposite the reference position (arms dangling). In extension, it leads the arm backward to a maximum amplitude of 60°.

In abduction/adduction the axis of rotation is conveyed by the articulation of the shoulder in a sagittal plane, from front to back. The abduction of the arm is effectuated in a frontal plane in a movement passing by the exterior, leading the arm to the vertical position for a maximum range of 180°, hands in the air, similar to the maximum flexion seen above. The opposite pole, of adduction, has the arm pass in front of the chest in a movement whose maximum range is 60°. The mobility of the last degree of freedom of the arm, called horizontal flexion/extension is carried out on a horizontal plane. It would seem that this degree of freedom is entirely contained in the composition of movements of the first two brachial dimensions described above. It then becomes an artefact, which is perfectly replaceable by brachial flexion/extension and abduction/adduction in combined movements. This brings the number of dimensions to 28 for the upper member in its entirety.

Gestures: some physiological constraints

The necessity for an inventory of geometrical relationships

This presentation of the degrees of freedom and of the movements that they allow gives little idea of co-articulation phenomena, for which two or three dimensions or even two segments form an anastomosis3. It does not give any idea of the dynamic joining up of spaces. In fact, the movements are determined by the articulatory physiology, and their directions are determined by the limits permitted by the articulations. In this way, involuntary transfers of movement obey rules derived from the often-changing geometrical relationships that are held between differing degrees of freedom. We must therefore take an inventory of these.

Certain degrees of freedom are reduced in amplitude. The pronation that develops normally to 85° covers no more than 45° in a position of maximal flexion in the forearm, i.e. when the hand is level with the neck. Similarly, the flexion/extension of the hand is reduced in a position of strong manual abduction/adduction. The inverse situation is true. The adduction does not exceed 30° in a position of pronation, whereas it develops up to 45° in the other positions.

The coincidence of rotational axes

Added to these reductions of amplitude in a range of movement, certain rotational axes can at times coincide. When the forearm is in total extension, the rotational axis appertaining to the interior/exterior rotation of the forearm (along the arm) coincides with that of the pronationsupination (along the forearm), a movement affected to the hand.

We may remark that the rotational axes exhibit a variable geometry. Thus, for manual abduction/adduction, the rotational axis crosses the wrist from one end to the other following the interior/exterior axis of the wrist. This is effectuated in a place so close to the hand that a position of total flexion or of total extension re-orientates this rotational axis in a plane which is nearly coincidental to the axis of pronation-supination (along the forearm). Therefore, for these positions of total flexion/extension, the distinction between abduction/adduction and pronation-supination becomes unclear. There is no longer any independence in degrees of freedom. Moreover the bonding between abduction/adduction and pronation-supination increases to the extent that one approaches a maximal position of flexion or of extension. Thus, for a position of great flexion, a voluntary movement of supination never fails to cause a movement induced by abduction. With a movement of pronation, the hand orientates itself towards an adduction. Generally speaking, the bonding between the poles is reversed (see figure 2 below).

The dynamic joining up of spaces

If we retrace the segments one after another, the arm reveals a paradox which bears the name of its discoverer: the Codman paradox. From an initial position in which the forearm and arm are aligned along the side of the body and in which the fingers are pointing downwards, the thumb pointing slightly forward (A, below), a movement of abduction of the arm to 180° (movement in a frontal plane on the side) brings all these segments to the vertical and above the shoulder (B and C). Through a movement of extension of the arm by 180°, bringing it in this way into the initial position, the whole group of segments passes in front, describing an arc in the sagittal plane (D): this time, the thumb is turned backward, while the palm is oriented toward the exterior (E).

The two degrees of freedom are located in the domain of the shoulder. This has induced a double movement which appears on the hand: there has been a total interior rotation of 90° and a total pronation of 85°; the whole group of segments has imposed an involuntary rotation of 175° on the hand. On the one hand, the abduction/adduction provokes an induced movement of interior rotation and of pronation, in the case of a voluntary movement of abduction, and on the other hand, it provokes exterior rotation and supination in the case of an adduction. This involuntary action on two segments -the forearm and the arm -is cumulative: it first affects the dimension of the forearm, and then exerts its influence on the hand, simultaneously with the slowing of rotational movement in the forearm.

A B D E C
As each segment is dependent upon another, we can qualify this as a dynamic joining up of spaces. On the one hand, each degree of freedom determines a space and on the other, this transitory fusion takes place during a movement.

Such a joining up of degrees of freedom also appears in the forearm. When it moves simultaneously in the field of its two dimensions, rotation interior/exterior and flexion/extension, this affects the pronation-supination through an involuntary movement. For an initial position in which the forearm is flexed at 90° and in which the fingers are pointing forward, the palm turned toward the interior and the thumb oriented upwards, the forearm shifts following an interior rotation bringing it into contact with the abdomen; then, in a combined movement of flexion and of exterior rotation, the hand is brought in front of the shoulder. Finally, the hand is brought back to its initial position through the extension of the forearm, which reveals the induced movement. We can then notice that the palm is turned upwards and the thumb is turned outwards: an induced movement of supination has affected the hand during the combined movement of flexion and of exterior rotation. This dynamic joining up of spaces, which leads to a paradox like Codman's paradox, is orientated according to the amplitude of rotational movement and of the flexion/extension (as can be seen in the list of consequences below). It is the amplitude incurred that gives the order of priority between the degrees of freedom; the pole of induced movement, whether it be pronation or supination, depends on this ordering.

Schematisation of joining sequences

The closer we come to the maximal amplitude of one of these dimensions of the forearm, the greater the involuntary movement in the hand will be.

Flex. + Rot. Int. > Pro.

Rot. Int + Flex > Supi. Exten + Rot. Int > Supi. Rot. Int + Exten. > Pro. Flex + Rot. Ext. > Supi. Rot. Ext. + Flex > Pro. Exten. + Rot.Ext. > Pro. Rot. Ext. + Exten > Supi.

Figure Example 1: List of joining sequences from the forearm on the hand

Here again, an initial position in maximal pronation-supination can block the complete playing out of the double voluntary movement that induces this pronation or this supination. This blockage increases to the extent that one approaches the maximal amplitude of one of the dimensions identified for the forearm.

The hand, affected by the joining between three degrees of freedom, corresponds exactly to the same conditions of movement (the necessity of a dynamic principle) of polar inversion for the consequences induced, and of the reduction in amplitude for extreme initial positions (flexion/extension reduced in strong abduction/adduction and vice versa). In this sense, one could qualify this bonding as a dynamic joining up of spaces. The list of involuntary consequences for the movement of the two other degrees of freedom for the hand can be schematised in the form of a star (to be read according to the order of the list).

Schematisation of gestures

We have determined a schema for the dynamic joining up of spaces by segments. This gives a measure of interdependence which is held between the degrees of freedom. Thus, the number of involuntary movements allows us to predict the consequence for other gestural segments that are initially effectuated on a given segment.

A gesture that begins at the arm will have involuntary and inertial consequences on the forearm and/or the hand; these secondary movements can themselves provoke an intra-or inter-segmental transfer of movement. The circulation of voluntary or involuntary transfers exerts a lasting influence on this complex system of 28 degrees of freedom and the joining sequences that we have seen reduce the number of dimensions which are effectively at work in the unfolding of a gesture.

For a proximal-distal flux

For a gesture which begins in the arm, its unfolding is schematically presented as follows: the movement begins in the arm (see the lowest line, Fig. 3) then it is transferred to the forearm (middle line) and travels up through to the hand (top line). This shows the alternating of inertial and dynamic transfers. The gesture begins with a double voluntary movement of abduction and of flexion of the arm. In (1) abduction is induced by dynamic joining, an interior, involuntary rotation of the forearm; followed, in (2), by a flexion of the arm transferred to the forearm. The consequence of this double joining on the forearm (interior rotation and flexion) leads to a new dynamic joining which becomes an involuntary supination in the hand, in (3). Almost simultaneously (4), the flexion of the forearm moves up to the hand by a transfer that is losing its strength. This explains the order supination + flexion, in (5), which involuntarily passes on a manual adduction, again by joining. The last movement of this gesture: given the position of the hand at the moment when adduction appears, a weak transfer to the forearm by an interior rotation, concludes the sequence of movements. This trans-segmental schema distributes the mobility of the arm over six degrees of freedom, or dimensions, starting with a voluntary and controlled movement of only two dimensions.

For a distal-proximal flux

If the propagation of movement be effectuated following a flux moving from a proximal segment toward distal segments, the opposite can happen: the mobility of a gesture can spread in a distal-proximal flux. Thus, the movement starting from the hand spreads to the forearm. The top line represents the schema for the hand, and the bottom line the consequences on the forearm. Without giving the detail of the order for movement transfers, the two voluntary movements are represented here by adduction and extension concerning the hand. All else results form the dynamic joining and geometrical orientations of the axes.

Articulatory schemas for 32 gestures

All of the schemas for the hand, the forearm and the arm are shown below in the form of Gestural Units (henceforth GU) which group together movements over several segments determined by physical and physiological transfers, all beginning with a double voluntary movement of two degrees of freedom for a segment (underlined in each GU). The left side of the table concerns those UG with pronation, and the right side concerns those effectuated with supination; in the top part of the table, the gestures of the hand are composed with adductions whereas the lower part brings together GU where the movements of abduction are present in the schema of the hand.

In this table of 32 GU, the rotation of the forearm is abbreviated by the denomination of its two poles (EXTerior and INTerior). The other abbreviations use the first letters of each pole (PRO for pronation, FLEX for flexion). Each GU is numbered. In the text across from this numbering, the 1st line represents the hand, and the 2nd, the forearm; any exceptions are noted in parentheses. Each section groups together all those poles for the degrees of freedom of the hand which are identical; only the quantity of movement or the order varies.

For the totality of the matrix, the voluntary part of the gesture only acts on two dimensions, whether the fingers, hands, forearms or arms are concerned. The other components of each GU derive from the transfer of the quantity of movement according to the determinations seen above. Nothing else governs the unfolding of these gestures. We might say that these are simple GUs. They spread their projections to several segments according to an envelope, rather than in a single form Each form unfolds according to a determined order of sequencing. This kind of morphological programme harnesses the substratum, in this case the upper member, and all or part of its zone of influence according to its manifestation. Within this zone, the form is manifested according to different amplitudes. Moreover, each manifestation of this gestural form can be sketched, using a single characteristic. The gestural unit remains the same.

Segmental centres of organisation

The nature of these dimensions contributes to the determination, whether it be that of the flux in the propagation of movements, that of the number of degrees of freedom under influence (and therefore of the number of segments in the zone of influence), or that of the segment where gestural units occur. Finally, the position of degrees of freedom in the schemas of each GU can give an idea of the quantity of movement which characterises each one of the poles at play. The more a pole nears the first place, the greater the quantity of movement in its own matrix of amplitude becomes. In the table below, the abbreviations in capital letters show the sizeable quantities of movement in relation to their position in the schema.

Gestures 1) and 3), like gestures 2) and 4) (and also 17 and 19; 18 and 20) are noteworthy only for the quantity of movement either in the hand or in the forearm. In this formal proximity between gestures their place of organisation can be discerned: for these cases, when the movement of adduction or of abduction, in second position is greater, the organising centre of the gesture is the hand, whereas when the quantity of movements is smaller, it is the forearm. In other words, gestures 3, 4, 19 and 20 are organised in the forearm; this segment structures the projected form on the upper member. Which rules can explain how the forearm is able to structure the GUs? Generally speaking, the forearm organises the GU whenever the degree of freedom in the 1st position of the schema of the forearm as a flexion or an extension, and when the abduction or the adduction of the schema of the hand is in 2nd position due to a small quantity of movement (3, 4 19 and 20). I have thus determined the rules for the appearance of a centre of organisation in the forearm, as well as those for the arm, the hand and the fingers (see [START_REF] Boutet | Approche morpho-dynamique du sens dans la gestuelle conversationnelle[END_REF]. While the forearm structures the GUs, manifestations concerned only with the hand conserve identity. The degrees of freedom of the hand in movement thus constitute nothing more than an anamorphosis that conserves gestural identity intact, even if they are the only segments to move. We observe here a veritable formal harnessing that creates a morphological relation which is at times foreign to a visual modality, as we shall see shortly. The segment that moves then behaves like a simple support.

Proprioceptive identities

In this view, GU 22 is organised at the level of the arm segment with the strongest inertia, like the GUs that display abduction/adduction for the arm at the beginning of the schema (5, 6 and 21). It propagates its influence up to the hand through a proximal-distal flux and even moves up through a distal-proximal flux starting with the hand: it reverses the last degree of freedom in the schema of the hand (ABD) through its opposite pole (ADD). In GU 22, abduction is transformed into adduction to result in GU 14. As this last pole has the amplitude necessary to move, it is in the first position of the new schema of the hand (GU 14 henceforth) while the poles of the two other dimensions of the hand remain unchanged. Naturally, another form appears on the forearm. This GU 22, which spreads its influence to another gestural unit ( 14), can be translated by "impotence". In both cases we can follow the movement of the arm and the hand, which evoke gestures typical of the expression of "impotence".

In the same way, a shrugging gesture will be interpreted as the expression of an impossibility to act. If these three gestures (22, 14 and shrugging) are visually quite different, they are morphologically linked by physiological constraints. These gestural manifestations correspond in fact to a single GU.

The double morphological relation, considered on the one hand as form and on the other as semantic, and consequently as a morpheme, appears for the gesture as "impotence" and does not depend on a visual model. The directions of the manifestations and the affected segments are so different that they offer proprioception as their only structuring modality. If vision, in its role as a modality for apprehending gestural phenomena allows the receiver to gain access to forms, it does not allow him/her to gain access to anamorphoses, since it has no direct access to the planes of projection. Vision is in fact merely the reception of scattered traces. However, the general impression of these GUs lies in physiological phenomena which build up systems of reference in centres of segmental organisation, whose intersections of projected manifestations although entangled, still remain distinct.

The gestural as substratum and as support

Without going into detail on the labels of the 32 GU presented above, 28 stand out. They all display this dual morphological and semantic relation, and all are organised on segments. On the one hand, vision gives us access to traces in a sense diffracted to the far-flung corners in zones of determined variation (the manifestations of the same GU). On the other hand, the formal justification for gestures using an imagistic iconicity does not function here.

The respective referents of "impotence" (22 and 14), of "leave" (25) or of "refuse" (7), which do not correspond to objects, cannot be defined by quasi-biological anchoring (loss of energy for "impotence" contradicted by the shrugging of shoulders) or by characteristics vectorizing an egocentric space (the case of manifestations of the gesture "leave" nevertheless directed towards oneself). It seems to say the least that iconicity passes by the body, without the vision of the latter giving a direct access to signifying forms. Here, it is the body itself that generates a model of iconicity.

Figure

  Figure Example 2: Figure of joining sequences between degrees of freedom for the hand.

Fig. 3 :

 3 Fig. 3: The proximal-distal flux of a gesture

  Figure Example 4: The distal-proximal flux of a gesture

If the gestures take place in the range indicated, their forms are, a priori, capable of occupying a

28dimensional space. Only pointing escapes this structuring. Its indexical function points in the distance and abstracts the member from its own form.2 The degrees of freedom of the hand are all defined according to its position of reference. The arm and the forearm, as its prolongation, remain at the side of the body; the palm of the hand is turned towards the front, the fingers orientated downwards. The degrees of freedom of the hand and their rotational axes are thus defined relative to this position, with the exception of pronation-supination (see infra).

By analogy with its acceptation in anatomy, anastomosis here signals the joining up of two conduits having the same nature, segments or degree of freedom.