Meriem K Abderrezak

Kristýna Šichová

Nancy Dominguez-Boblett

Antoine Dupé

Zahia Kabouche

Christian Bruneau

Cédric Fischmeister
email: cedric.fischmeister@univ-rennes1.fr

Cross-metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

Keywords: Cross-metathesis, ruthenium catalysts, epoxide, tandem reactions

The cross-metathesis of 1,2-epoxy-5-hexene 1 with methyl acrylate and acrylonitrile was investigated as an entry to the synthesis of polyfunctional compounds. The resulting cross-metathesis products were hydrogenated in a tandem fashion employing the residual ruthenium from the metathesis step as the hydrogenation catalyst. Interestingly, the epoxide ring remained unreactive toward this hydrogenation method. The saturated compound resulting from the cross-metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy-alcohol and an amino-alcohol in high yields.

Introduction

Catalytic carbon-carbon double bond transformations by olefin metathesis have significantly impacted organic and polymer synthesis over the last two decades [START_REF]Handbook of metathesis[END_REF][START_REF]Theory and Practice[END_REF][START_REF] Mutlu | [END_REF].

If early works focused on Ring Closing Metathesis and Ring Opening Metathesis

Polymerization, progresses in catalysts performances [4,5] and selectivity have enabled the achievement of more challenging transformations such as crossmetathesis reactions [6], stereoselective transformations [7] including the selective synthesis of Z-olefins [8][9][10][11]. Recently, the cross-metathesis of renewable compounds with electron-deficient olefins was developed as a straightforward way for the synthesis of difunctional compounds suitable for polymer syntheses [12][13], fine chemicals [14][15][16][17], or as key synthetic tool in multi-step syntheses of complex molecules [18][19][20][21]. Cross-metathesis with functional olefins is of great interest as it offers the possibility for post-transformation of the functional group. For example we have shown that cross-metathesis with acrylonitrile run in a tandem fashion with hydrogenation delivered amine derivatives [22] whereas the tandem crossmetathesis/hydrogenation with acrolein delivered the corresponding alcohols [23][24].

Nice examples of cross-metathesis/non-metathesis sequences have also been reported by Andrade in 2011 [25].

In this article we present our results aimed at extending the scope of sequential transformations including cross-metathesis to the synthesis of trifunctional compounds. Several examples involving the cross-metathesis of a commercially available epoxide-containing olefin with methyl acrylate and acrylonitrile and their subsequent transformations leading to multifunctional building blocks are reported.

Results and Discussion

Cross-metathesis reactions involving electron-deficient olefins are generally challenging transformations as they are substrate dependent and therefore require optimization of experimental parameters. For instance, while cross-metathesis with methyl acrylate turns out to be a rather straightforward transformation, crossmetatheses with acrylonitrile, acrylamides or acrolein are much more demanding transformations [13,14,24]. We have investigated the reactivity of 1,2-epoxy-5hexene 1 with methyl acrylate and acrylonitrile and further exploited the versatility of the epoxide ring to prepare trifunctional molecules by ring opening of the epoxide. To date, 1 has been scarcely used in olefin cross-metathesis transformations. In some examples, Grela used 1 as a test substrate to evaluate the efficiency of new catalysts, [26] and Cossy prepared vinyl functionalized oxazoles [27]. To our knowledge, the cross-metathesis of 1 with electron-deficient olefins has not been reported. The cross-metathesis of 1 with methyl acrylate was thus investigated under various conditions of solvents, catalysts and concentration (Scheme 1). As required in cross-metathesis reactions of electron-deficient olefins, an excess of methyl acrylate was employed and a temperature of 80 °C was necessary to ensure high conversion. Reactions were carried out in dimethyl carbonate, a solvent compatible with ruthenium olefin metathesis catalysts [28] while being much greener than toluene or dichloromethane commonly used in such reactions [29]. Based on our previous results and observations in various cross-metathesis reactions, the phosphine-free Hoveyda type second generation Zhan catalyst-1B [START_REF] Zhan | Ruthenium complex ligand, ruthenium complex and the use of the complex as a catalyst in olefin metathesis reactions[END_REF] was selected to conduct this transformation. A recent study by Fogg rationalized the superiority of Hoveyda catalyst vs Grubbs catalyst in cross-metathesis with acrylates showing that the phosphine could interact with the electron-deficient olefin [31].

Scheme 1: Cross-metathesis of 1 with methyl acrylate

As observed by us and other groups in cross-metathesis involving different substrates, double bond migration side-reactions took place during this transformation. This side reaction could be circumvented using benzoquinone [32] as an additive to decrease the extent of double-bond migration. As depicted in Table 1 (entries 1-4), 10 mol% of benzoquinone were necessary to ensure a limited amount (< 10%) of side products resulting from double-bond migration. However, addition of benzoquinone resulted in slower reaction hence a catalyst loading of 2 mol% was necessary to restore full conversion within 2h (entry 4). In this case the product was isolated by distillation [START_REF]Purification by column chromatography on silica gel resulted in very poor yields likely due to epoxide decomposition. 34[END_REF] in 69% yield as the sole E-isomer [34]. The transformation was sensitive to the concentration of the reagents and required a concentration of 0.5 M to operate with full conversion. This characteristic was previously observed in cross-metathesis of fatty acid methyl esters with methyl acrylate [13]. Finally, neither toluene as solvent nor Hoveyda 2 nd generation catalyst have lead to improvements of the reaction performances (entries 7, 8).

Table 1. Cross-metathesis of 1 with methyl acrylate a

Similarly, the cross-metathesis of 1 with acrylonitrile was conducted to furnish the bifunctional derivative 3 in 71% yield as a mixture of stereoisomers. In that case, high conversions and yields could only be obtained by means of slow addition of the catalyst and high dilution (Scheme 2) [13]. As we already observed, [13][14]22] together with other groups, [START_REF] Zhang | [END_REF][36] and Z (major) stereoisomers.

Scheme 2: Cross-metathesis of 1 with acrylonitrile

With these two compounds in hands, we turned our attention to their post-metathesis transformations. First, we looked at the hydrogenation of the carbon-carbon double bond in compounds 2 and 3. Typically, there are several ways to perform the hydrogenation of a carbon-carbon double bond resulting from a cross-metathesis reaction. A possibility consists in the Pd/C catalyzed hydrogenation of the isolated product. This method presents the advantage of being effective at room temperature under a low hydrogen pressure [37][38]. However, such hydrogenations are in general carried out on purified products but more importantly in the present case, such conditions may result in the carbon-carbon double bond hydrogenation accompanied by ring opening of the epoxide leading to a mixture of primary and secondary alcohols [39]. A second and more straightforward method consists in the tandem metathesis/hydrogenation reaction where the residual ruthenium species arising from the metathesis step serve as the hydrogenation catalyst [13,[22][23][24][START_REF] Fürstner | For an early example[END_REF].

In general, this protocol requires higher temperature and pressure but it does not need additional costly catalyst and it can be performed without isolation of the intermediate olefin hence saving time and energy-consuming workup procedures [START_REF] Zieliński | milder transfer hydrogenation conditions have recently been reported[END_REF]. To the best of our knowledge, such tandem procedure has not been applied to an epoxide containing olefin. Compound 2 was prepared as described here above (Scheme 1) and the reaction mixture was directly transferred into a high pressure reactor without any workup. Remarkably, following the hydrogenation step carried out under 20 bar of hydrogen at 50 °C, the 1 H NMR of the crude reaction mixture revealed the presence of the epoxide moiety without any traces of diol. This tandem procedure delivered the saturated compound 4 in a satisfactory 53% yield for two steps (Scheme 3). The tandem cross-metathesis of 1 with acrylonitrile followed by hydrogenation of the intermediate compound 3 was conducted similarly. In this case a higher hydrogen pressure (45 bar) was necessary to reduce the carbon-carbon double bond. Nevertheless, under these conditions, the epoxide-containing product 5

was isolated in a satisfactory 46% yield for two steps without any traces of diol detected in the crude 1 H NMR of the reaction.

Scheme 3: Tandem cross-metathesis/hydrogenation

With this protocol secured, we turned our attention to the synthesis of useful polyfunctional building blocks. Thus far, the post-transformation of the electrondeficient olefin cross-metathesis partner has received attention for the synthesis of polymer precursors. For instance, we have reported the reduction of the nitrile functional group into primary amine [22] and the reduction of the formyl group into alcohol [23][24]. Herein, we focused on the post-transformation of 4 by ring-opening of the epoxide moiety. The diol 6, methoxy-alcohol 7 and amino-alcohol 8 were thus prepared by reacting 4 with water, sodium methoxide and aniline, respectively (Scheme 4). The synthesis of 6 proceeded cleanly and did not require any purification procedure (see supplementary data). Similarly, the synthesis of 7 proceeded cleanly and delivered a single regioisomer 7 in quantitative yield. Finally, the amino alcohol 8 was also obtained as a single regioisomer in 61% yield (Scheme 4).

Scheme 4:

Trifunctional compounds obtained by ring-opening of epoxide 4

In conclusion, we have shown through selected examples that cross-metathesis of an epoxide containing olefin with electron-deficient olefins constitutes a versatile entry towards trifunctional building blocks by ring-opening of the epoxide. We have shown that the tandem cross-metathesis/C=C hydrogenation yielded the hydrogenated compound without altering the epoxide moiety that was further efficiently transformed into a 1,2-diol, a 1,2-alkoxy-alcohol and a 1,2-amino-alcohol. This strategy opens the way for numerous potential transformations involving the epoxide but also the functional group of the electron-deficient olefin. In particular, lactones should be accessible by intramolecular trans-esterification from 6, 7 and 8, as well as cyclic amines by intramolecular cyclization involving primary amine resulting from hydrogenation of the nitrile functionality in 5. All these aspects will be further developed in our group.

Acknowledgements (optional)

The authors are grateful to the Region Bretagne and ADEME for a PhD grant to A.D and to MESRS for a grant to M. K. A. We also acknowledge the European Erasmus+ programme for grants to K. S. and N.D.-B.

Supporting Information (if any)

Full experimental details and characterizations are provided in the supporting information.


Dr Yanan Miao

Dr Antoine Dupé

Christian Bruneau
email: christian.bruneau@univ-rennes1.fr

Dr Cédric Fischmeister
email: cedric.fischmeister@univ-rennes1.fr

Ruthenium Catalyzed Synthesis of 1,2-diketones from Alkynes

Keywords: Keyword 1, Keyword 2, Keyword 3, Keyword 4, Keyword 5))

Catalysis / Oxidation / Ruthenium / 1,2-diketones / alkynes

The ruthenium catalyzed synthesis of 1,2-diketones by oxidation of alkynes with sodium hypochlorite has been investigated. RuO 4 in situ generated from inexpensive RuCl 3 ,xH 2 O and NaOCl demonstrated high performance at room temperature in diethyl carbonate as reaction medium. A variety of diketones were prepared in good yields using this environmentally friendly procedure.

Introduction

1,2-Diketones are useful building blocks in organic synthesis in particular for the synthesis of heterocyclic compounds of biological interest. [1] 1,2-Dicarbonyl compounds are also precursors for the synthesis of N-Heterocyclic Carbenes (NHC), a prominent class of ligands in organometallic chemistry and catalysis. [2] During the past 15 years many examples of catalytic synthesis of 1,2diketones have emerged in particular the oxidation of internal alkynes has received most attention as a result of the accessibility of a broad variety of substrates that can be obtained by Sonogashira cross-coupling reactions. These catalytic methods are undeniable progress making these protocols more environmentally friendly as compared to stoichiometric oxidation protocols employing for instance thallium, manganese, chromium or mercury salts. [3] A variety of transition metals have been reported for the oxidation of alkynes into 1,2-diketones. Rhenium [4] and Pd-catalyzed [5] processes employing hydrogen peroxide, dioxygen, sulfoxides or pyridine N-oxide as oxidant were reported. These catalysts displayed in general very good performances with diarylalkynes but they required high catalyst loading (5-10 mol-%) and/or high temperatures (60-140 °C). [6] An interesting Au/Ag catalytic system employing diphenylsulfoxide as oxidant was recently reported as an efficient system for the synthesis of benzil derivatives and keto imides. [7] However, best performances were obtained in refluxing dichloroethane, a solvent that is no longer usable in the pharmaceutical industry. [8] Iron catalysts have been reported since the early work by Sawyer in 1990 [9,10] and recently, FeCl 3 (5 mol%)/H 2 O 2 was found to be an efficient catalyst for room temperature oxidation of electron rich diarylalkynes. [11] Recently, an interesting copper catalyst operating under mild conditions with O 2 /H 2 O as the oxidant was disclosed. However, the use of selectfluor to generate the active catalyst might hamper the interest of this method. [12] Ruthenium catalysts in particular RuO 4 play a major role in oxidation catalysis. [13] In fact, regarding the oxidation of alkynes into diketones, a literature survey shows that RuO 4 /NaIO 4 oxidation of alkyne into diketones is the most widespread procedure [14] despite the requirement for highly toxic solvent (CCl 4 ) and oxidant. For these reasons, decreasing the environmental impact of Ru-catalyzed oxidation reactions is a topic of high interest. In 2010, Wan reported a very efficient catalyst composed of [RuCl 2 (p-cymene)] (0.001 mol-%)/I 2 (10 mol-%) and TBHP as oxidant. [15] However, this system required several hours in dioxane at 80 °C. Later on the same group reported a room temperature catalytic process consisting in a complex mixture of [RuCl 2 (p-cymene)] 2 , TEMPO, oxone, NaHCO 3 in nitromethane and water as reaction media. [16] As depicted in all these examples, oxidation of alkynes into 1,2diketones still suffers in many cases from harsh conditions, high catalyst loadings and/or the use of oxidants and solvents of high environmental impact. Herein we present our studies aimed at decreasing the environmental impact of the ruthenium catalyzed oxidation of alkynes. In particular, we have focused our study on the use of carbonate solvents and sodium hypochlorite as oxidant.

Results and Discussion

In our ongoing efforts on the sequential transformation reactions involving an initial metathesis transformation, we have been investigating tandem metathesis/oxidation reactions. Although the initial goals were not reached, we observed, as reported by Dragojlovic, [17] that dimethyl carbonate (DMC), a solvent recently introduced in olefin metathesis transformation as a greener alternative to toluene and dichloromethane, [18,19] was truly compatible with oxidant media. [START_REF] Schäffner | carbonates as solvents in catalysis[END_REF] This is particularly highlighted by the high yielding oxidative cleavage of alkene into aldehyde, a reaction usually carried out in CCl 4 /H 2 O media (Scheme 1).

Scheme 1 Alkene oxidative cleavage in DMC/H2O

Following this result we turned our attention to the RuCl 3, xH 2 O catalyzed oxidation of diphenylacetylene (tolane) employing DMC as reaction media (Scheme 2). NaOCl was initially evaluated as the "greenest" oxidant that can be used without specific equipments [START_REF]Considering O2 or O3 as oxidants[END_REF] considering that H 2 O 2 is not appropriate to generate RuO 1, entry 1). Careful analysis of the reaction mixture showed the presence of benzoic acid, a side product that was previously encountered in several studies on the oxidation of alkynes including the early report on RuO 2 /NaOCl/CCl 4 /H 2 O oxidation of alkyne. [22] Reduction of the excess of oxidant was not efficient to suppress the formation of benzoic acid. In addition to benzoic acid, the dichloro derivative PhClC=CClPh was also detected by GC/MS. The formation of chlorinated product is often encountered upon using NaOCl but this issue is efficiently solved by using buffered solution with a pH>10. [23] Indeed when the reaction media was buffered at pH= 12 the chlorinated product formation was suppressed and the yield of 2 increased ( 2, none of the tested precursors led to improved performances. Of note, the complex [RuCl 2 (p-cymene)] 2 that led to the best results with the Wan conditions [16] did not reach the performances of RuCl 3 ,xH 2 O.

Table 2. Catalyst precursors screening [a] Entry Catalyst Conv. (%) [b] Yield [c] 1

RuCl3, xH20 >98 [d] 82 2

[Ru(COD)Cl2]n 90 79 3 Ru(dppe)2Cl2 73 [e] n.d. [f]

4

[RuCl2(p-cymene)]2 [g] >98 [d] 74 5

RuCl2(p-cymene)PPh3 77 68 6

RuCl2(PCy3)2(=CHPh) 90 79 7RuCl2(SIMes)(PCy3)(=CHPh) 68 n.d. [f]

8

IrCl3.3H2O 0 0

[a] 1 (0.5 mmol), catalyst (0.5 mol-%), NaOCl (3 equiv.), DEC (5 mL), r.t., 2 h. [b] Determined by gas chromatography using hexadecane as internal standard. [c] Isolated yield. [d] 1 was not detected by gas chromatography.

[e] after 6 h.

[f] not determined. [g] 0.25 mol%
The scope of the reaction was explored with a variety of internal alkynes easily prepared by palladium catalyzed Sonogashira coupling. In particular, the influence of steric and electronic parameters was evaluated. Good yields were obtained with diphenylacetylene derivatives substituted with an electron donating group including a sterically hindered substrate. The situation was somewhat different when electron withdrawing group were installed on the substrates. In these cases (Table 3, entries 3-9) and despite the almost full conversion obtained, the 1,2-diketones were isolated in moderate to good yields. As it will be discussed later this feature could be rationalized with mechanistic considerations. However, it must be mentioned that this lower reactivity of electron withdrawing substituted alkynes is a general problem observed in the oxidation of alkynes. [5,11, 14d, 16] Likewise, aliphatic alkyne usually display lower reactivity leading to modest yield.

Table 1. Oxidation of tolane [a] Entr y

Solvent NaOCl (equiv.) t (h) Conv. (%) [b] Y (%) [c] 1 DMC 4 4 > 98% [f] 69 2 DMC 3 4 76 34 3 [d] DMC 3 4 65 51 4 [e] H2O 4 4 0 0 5 DEC 4 4 >98 [f] 86 6 DEC 2 4 46 n.d. [g] 7 DEC 3 4 >98 [f] 86 8 DEC 3 2 >98 82 9 [h] DEC 3 8 46 n.d. [g,i] 10 [j] DEC 3 5.5 >98 [f] 86 11 [k] DEC 3 2 62 39 12 [l] DEC 3 2 83 59 13 [m] DEC 3 2 0 0

[a] 1 (0.5 mmol), RuCl3.3H2O (0.5 mol-%), [1] = 0.1 mol/L, r.t., argon atmosphere. [b] Monitored by GC using hexadecane as internal standard.

[c] Isolated yields. [d] Buffer solution (Na2HPO4/NaOH, pH= 12). [e] No reaction. [f] 1 was not detected by gas chromatography. [g] n.d = not determined.

[h] T= 5 °C. [i] Benzoic acid was detected.

[j] 0.1 mmol-% RuCl3.3H2O. [k] [1]= 0.5 mol/L. [l] [1]= 0.02 mol/L. [m] no catalyst
Based on the oxidation of alkenes mechanism, it was generally accepted that the RuO 4 oxidation of alkynes to 1,2-diketones involved a [3+2] cycloaddition. [13b] This hypothesis was confirmed in 2000 by Che et al. who presented the first evidence for [3+2] cycloaddition in the alkyne oxidation by a cis-dioxoruthenium(VI) complex. [24] In 2004, Yang et al. proposed a mechanism for the oxidation of alkynes into acids in which the generated 1,2-diketone undergoes a Baeyer-Villiger type oxidation by peroxymonosulfate leading to an acid anhydride which upon hydrolysis leads to a carboxylic acid (Scheme 3). [25] Scheme 3 Suggested mechanism for formation of carboxylic acids from diketones Based on these investigations, a tentative mechanism for the RuCl 3, xH 2 O/NaOCl oxidation of alkynes is proposed in Scheme 4. A [3+2] cycloaddition between the in situ generated RuO 4 and the alkyne generates the metallacycle B, which undergoes a rapid electrocyclic fragmentation to the desired 1,2-diketone C and RuO 2 . Similarly to Yang mechanism (Scheme 3), the cleavage of the diketone by NaOCl would proceed by a nucleophilic addition of the hypochlorite ion to the carbonyl functional group affording the intermediate D. A Baeyer-Villiger type rearrangement would further lead to the acid anhydride E and subsequently to the corresponding carboxylic acid. However, a test showed that benzil 2 was indeed converted into benzoic acid upon reaction with NaOCl under basic conditions with or without RuO 4 [26,[START_REF]Commercially available anhydride E was submitted to hydrolysis under neutral and basic conditions (NaOCl). The hydrolysis under neutral conditions was very slow as compared to the hydrolysis in a basic medium[END_REF] but these reactions were very slow and could not account for the total formation of benzoic acid. Hence other pathway(s) should be considered such as pathway II. Here, the ruthenacycle B undergoes a Baeyer-Villiger type rearrangement following addition of NaOCl (F) to furnish the anhydride E. Both mechanisms I and II are in agreement with experimental results as the nucleophilic addition of NaOCl on a carbonyl or alkenyl group should be facilitated by electron withdrawing substituent on the aromatic ring (R 1 in Scheme 4) hence leading to larger amounts of benzoic acid derivatives.

Conclusion

We have demonstrated that the ruthenium-catalyzed oxidation of alkynes into 1,2-diketones could be performed under environmentally acceptable experimental conditions. In particular, the use of NaOCl as unique oxidant with low loading of Table 3. Scope of the reaction [a] Entry Alkyne Product Conv. (%) [b] /Y (%) [c] 80/42 77/44 [d] 6 66/33 (90/28) [d] [a] Alkyne (0.5 mmol), RuCl3.3H2O (0.5 mol-%), NaOCl (3 equiv.), DEC (5 mL), r.t., 4 h. [b] Monitored by GC. [c] Isolated yield. [d] 8 h inexpensive RuCl 3 ,xH 2 O enabled the room temperature synthesis of a variety of 1,2-diketones in diethyl carbonate solvent. As encountered in most of the transition-metal catalyzed oxidation of alkynes, the reaction performed particularly well when electronrich diaryl alkynes were employed but performances dropped when electron-poor or aliphatic alkynes were employed. Despite this limitation, we believe that this protocol exhibits a favourable balance between cost and environmental impact on the one hand and yields on the other hand. Given the regulation strengthening regarding the use of toxic reagents and waste treatments, this protocol appears as an interesting alternative to the widespread oxidation process employing NaIO 4 in carbon tetrachloride.

8

Experimental Section

General Methods

All reactions were conducted under an inert atmosphere of argon using standard Schlenk tube techniques, unless otherwise mentioned. DMC and DEC were distilled and stored over 4A molecular sieves before use. NEt 3 was used as received and degased. Organic reagents were obtained from commercial sources and used as received. RuCl 3 , xH 2 O was purchased from Umicore Precious Metals. NMR spectra were recorded on Bruker 400 MHz spectrometers unless otherwise noted. Spectra are reported in ppm relative to residual chloroform (7.26 ppm for 1H NMRs and 77.0 ppm for 13 C NMRs). Coupling constants are reported in Hertz. GC-2014 Shimadzu Gas Chromatograph (Equity-5, 30m×0.25mm) were used to monitor the reaction. LRMS were recorded on GC-MS Shimadzu QP2010S apparatus. Products were purified by column chromatography on silica gel using mixtures of petroleum ether and ethyl acetate as eluent.

General procedure A: preparation of internal alkynes via Sonogashira coupling

A mixture of phenylacetylene (561.3 mg, 5.5 mmol, 1.1 equiv), halobenzene derivatives (5 mmol, 1.0 equiv), PdCl 2 (PPh 3 ) 2 (35.1 mg, 1 mol%), PPh 3 (26.23 mg , 2 mol-%) in 20 mL of NEt 3 was stirred for 5 min under an atmosphere of argon at room temperature. CuI (9.5 mg, 1 mol-%) was added and the reaction was sealed and stirred overnight at 60°C. The reaction mixture was filtered and the filtrate was washed with Et 2 O. The combined organic layers were washed with saturated NH 4 Cl solution, HCl (1 N), NaOH (1 N), brine and dried over MgSO 4 . After filtration the solvent was removed in vacuo. The residue was purified by silica gel chromatography to afford the pure alkynes.

General procedure B: oxidation of alkynes

A dry Schlenk tube was loaded with the solvent (DEC, 5 mL), hexadecane (gas chromatography standard; 20 μl) and the substrate (0.5 mmol). Catalyst RuCl 3 .3H 2 O (0.5 mol%) in solution and oxidant 13 wt% NaOCl solution (3 equiv) were added subsequently. The mixture was stirred at 25 °C (regulated oil bath temperature) and monitored by gas chromatography. The reaction was quenched with a saturated aqueous solution of Na 2 SO 3 and the organic layer was extracted with ethyl acetate (4×10 mL) and dried over Na 2 SO 4 . The combined organic layers were evaporated and the residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and petroleum ether.

Procedure for the oxidation of benzil 2

In a first experiment, a dry Schlenk tube was loaded with the solvent (DEC, 5 mL), hexadecane (gas chromatography standard; 20 μl) and 2 (0.5 mmol). A 13 wt.-% NaOCl solution (3 equiv) was added subsequently. The mixture was stirred at 25 °C (regulated oil bath temperature) for 4 h. The reaction was quenched with a saturated aqueous solution of Na 2 SO 3 and the organic layer was extracted with ethyl acetate (4×10ml) and dried over Na 2 SO 4 . Conversions were below 6 %. The aqueous phase was acidified to pH 4 by addition of 1N HCl and extracted with EtOAc. No benzoic acid could be detected in this organic phase.

A second experiment was carried out by first mixing for 2 h at r. t. RuCl 3 .3H 2 O (0.5 mol-%) and 3 equiv. of NaOCl in 5 mL of DEC. 2 (1 equiv.) was then added and the reaction stirred for 2 h at r.t. Again, conversions were below 5% and only traces of benzoic acid could be detected.

Product analyses 1-methoxy-4-(phenylethynyl)benzene 3

3 was prepared according to the general procedure A. Yellow solid; Yield: 88 %. NMR data are consistent with reported data. 28 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.51 (dd, J = 8.0, 2.0 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.35-7.30 (m. 3H), 6.88 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 159. 6, 133.0, 131.4, 128.3, 127.9, 123.6, 115.4, 114.0, 89.4, 88.1, 55. 1-methoxy-2-(phenylethynyl)benzene 4 4 was prepared according to the general procedure A. Yellow oil; Yield: 70 %. NMR data are consistent with reported data. 28 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.58 (d, J = 6.8 Hz, , 2H), 7.50 (dd, J = 7.6, 1.2 Hz, 1H), 7.40-7.25 (m, 4H), 6.96-6.90 (m, 2H), 3.92 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 159.9, 133.5, 131.6, 129.7, 128.2, 128.0, 123.5, 120.4, 112.4, 110.7, 93.4, 85.7, 55.8 Ethyl 4-(phenylethynyl)benzoate 5 5 was prepared according to the general procedure A. Yellow solid; Yield: 90 %. NMR data are consistent with reported data. 28 NMR (400 MHz, ) δ (ppm) 8.03 (d, J = 8.3 Hz, 2H), 7.59 (d, J = 8.3 Hz, 2H), 7.56-7.54 (m, 2H), 7.41-7.31 (m, 3H), 4.39 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 166. 1, 131.7, 131.5, 129.9, 129.4, 128.7, 128.4, 127.8, 122.7, 92.2, 88.7, 61.1, 14.3; LR-MS: [M] +. (C 17 H 14 O 2 ) m/z th. = 250, m/z found = 250.

4-(phenylethynyl)benzonitrile 6

6 was prepared according to the general procedure A. White solid; Yield: 83%. NMR data are consistent with reported data. 28 1 H NMR (400 MHz, CDCl3) δ (ppm) 7.64 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.58 -7.51 (m, 2H), 7.39-7.36 (m, 3H); 13 C NMR (ppm) (101 MHz, CDCl3) δ 132. 1, 132.0, 131.8, 129.1, 128.5, 128.2, 122.2, 118.5, 111.5, 93.8, 87.7 2-(phenylethynyl)benzonitrile 7 7 was prepared according to the general procedure A. Yellow oil; Yield: 82 %. NMR data are consistent with reported data. 28 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.69-7.54 (m, 5H), 7.47-7.32 (m, 4H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 132. 6, 132.3,132.1, 132.0, 129.2, 128.4, 128.2, 127.2, 122.0, 117.5, 115.3, 96.0, 85.6; LR-MS: [M] +. (C 15 H 9 N) m/z th. = 203, m/z found = 203.

1-chloro-4-(phenylethenyl)benzene 8 8 was prepared according to the general procedure A. white solid; Yield 81%. NMR dada are consistent with reported data. 28 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.55-7.50 (m, 2H), 7.46 (d, J = 8.5 Hz, 2H), 7.37-7.31 (m, 5H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 134.2, 132.8, 131.6, 128.7, 128.5, 128.4, 122.9, 121.8, 90.3, 88.2 ) 197.2, 136.2, 131.7, 131.6, 128.8, 128.4, 128.3, 128.2, 122.7, 92.7, 88.6, 26.6 1, 150.5, 132.7, 131.6, 128.3, 128.3, 123.1, 121.7, 121.0, 89.4, 88.5, 21. 5, 128.1, 127.4, 124.1, 90.4, 80.5, 30.8, 22.0, 19.1, 13.6 ) 194.8, 193.2, 165.0, 134.7, 133.3, 132.4, 129.9, 129.9, 126.2, 114.4, 55.7 7.91 (d, J = 7.6 Hz, 2H), 7.60-7.58 (m, 2H), 7.52-7.45 (m, 2H), 7.15-7.10 (m, 1H), 6.93 (d, J = 8.4 Hz, 1H), 3.56 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 194.8, 193.5, 160.4, 136.5, 133.7, 132.9, 130.4, 129.2, 128.6, 123.8, 121.5, 112.3, 55.6 ) 193.8, 193.7, 165.4, 136.0, 135.7, 135.1, 132.7, 130.0, 129.9, 129.7, 129.1, 61.6, 14.2 192.4, 135.9, 135.4, 132.7, 132.4, 130.2, 130.0, 129.2, 117.9, 117.5 ) 192.8, 192.0, 151.2, 137.3, 135.4, 132.4, 130.9, 130.0, 129.2, 124.1; LR-MS:

[M] +. (C 14 H 9 NO 4 ) m/z th. = 255, m/z found = 255.

1-(4-acetylphenyl)-2-phenylethane-1,2-dione 20 20 was prepared according to the general procedure. Yellow solid; Yield: 83%. NMR data are consistent with reported data. ) 197.2, 193.7, 193.6, 141.3, 136.0, 135.1, 132.7, 130.1, 130.0, 129.1, 128.7, 26.9 193.1, 168.5, 155.7, 134.9, 132.8, 131.6, 130.5, 129.9, 129.0, 122.3 ((Please adjust TOC Graphic to the size of this area; max. width 5.5 cm; max. height 5.0 cm))

Scheme 4

 4 Scheme 4 Proposed mechanism for 1,2-diketone formation

  3; LR-MS: [M] +. (C 15 H 12 O) m/z th. = 208, m/z found = 208.

  ; LR-MS: [M] +. (C 15 H 12 O) m/z th. = 208, m/z found = 208.

  LR-MS: [M] +. (C 15 H 9 N) m/z th. = 203, m/z found = 203.

  4 from RuCl 3, xH 2 O.

	RuCl 3 , xH 2 O	O
	NaOCl, solvent, r.t.	O
	1	2
	Scheme 2 RuCl3,xH2O /NaOCl oxidation of tolane 1
	Initial attempts were carried out in DMC at low RuCl 3, xH 2 O
	loading (0.5 mol%) employing 4 equiv. of sodium hypochlorite.
	Under these conditions the reaction proceeded with full conversion
	but diketone 2 was isolated in only 69 % (Table

Table 1

 1

	, entry 2, 3). If water as reaction media was not
	suitable either (Table 1, entry 4), replacement of dimethyl
	carbonate by diethyl carbonate resulted in the reduction of the
	amount of benzoic acid side product ensuing the isolation of 2 in
	86% and 82% after 4 and 2 h at room temperature, respectively
	(Table 1, entry 7, 8). Interestingly, no chlorinated product was

  1

		>98/83
	3
		13
	2
		>98/71
	4	14
	3
		96/63
	5
		15
	4
		96/61
	6
		16
	5
	7	17

4-(2-phenylethynyl)phenyl]ethanone 10 10 was

  prepared according to the general procedure A. White solid; Yield: 95%. NMR data are consistent with reported data. 7 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.94(d, J = 8.3 Hz, 2H), 7.61 (d, J = 8.3 Hz, 2H), 7.58-7.53 (m, 2H), 7.40-7.35 (m, 3H), 2.62 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm

	. LR-MS: [M] + (C 14 H 9 35 Cl) m/z th. = 212, m/z found = 212;
	(C 14 H 9 37 Cl) m/z th. = 214, m/z found = 214,
	(C 14 H 9 35 Cl)/(C 14 H 9 37 Cl)= 2.8
	1-nitro-4-(phenylethynyl)benzene 9
	9 was prepared according to the general procedure A. Yellow solid;
	Yield: 85 %. NMR data are consistent with reported data. 28 1 H
	NMR (400 MHz, CDCl

3 ) δ (ppm) 8.21

(d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.58-7.55 (m, 2H), 7.45-7.35 (m, 3H)

; 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 147.0,

132.2, 131.8, 130.3, 129.3, 128.5, 123.6, 122.1, 94.7, 87.5

; LR-MS: [M] +. (C 14 H 9 NO 2 ) m/z th. = 223, m/z found = 223.

1-[

  ; LR-MS: [M] +. (C 12 H 14 ) m/z th. = 158, m/z found = 158.

	1,2-diphenylethane-1,2-dione 2
	2 was prepared according to the general procedure B. Yellow solid;
	Yield: 82 %. NMR data are consistent with reported data. 5a, 10b, 15
	1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.98 (d, J = 7.3 Hz, 4H), 7.67
	(t, J = 7.4 Hz, 2H), 7.52 (m, 4H); 13 C NMR (101 MHz, CDCl 3 ) δ
	(ppm) 194.7, 135.0, 133.2, 130.0, 129.2; LR-MS: [M] +. (C 14 H 10 O 2 )
	m/z th. = 210, m/z found = 210.
	1-(4-methoxyphenyl)-2-phenylethane-1,2-dione 13
	13 was prepared according to the general procedure B. Yellow oil;
	Yield: 83%. NMR data are consistent with reported data. 15 1 H
	NMR (400 MHz, CDCl 3 ) δ (ppm) 7.96 (m, 4H), 7.63 (m, 1H), 7.50
	(m, 2H), 6.98 (d, J = 8.1 Hz, 2H), 3.88 (s, 3H); 13 C NMR (101
	MHz, CDCl 3 ) δ (ppm

  ; LR-MS: [M] +. (C 17 H 14 O 4 ) m/z th. = 282, m/z found = 282.

	4-(2-oxo-2-phenylacetyl)benzonitrile 16
	16 was prepared according to the general procedure B. Yellow
	solid; Yield: 61%. NMR data are consistent with reported data. 16
	1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.08 (d, J = 8.5 Hz, 2H),
	7.987 (dd, J = 7.3, 1.6 Hz, 2H), 7.81 (d, J = 8.5 Hz, 2H), 7.70 (m,
	1H), 7.54 (m, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 193.0,

  7 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.07 (m, 4H), δ 7.98 (d, J = 7.2 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.53 (dd, J = 7.4 Hz, J = 7.4 Hz, 2H), 2.66 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm

phenylacetyl)phenyl acetate 21 21 was

  ; LR-MS: [M] + (C 16 H 12 O 3 ) m/z th. = 252, m/z found 252. prepared according to the general procedure. Yellow solid; Yield: 64%. NMR data are consistent with reported data.29 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.02(d, J = 8.4 Hz, 2H), 7.96 (d, J = 7.2 Hz, 2H), 7.66 (t, J = 7.6 Hz, 1H),7.52 (m, 2H), 7.28-7.23 (m, 2H), 2.33 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 194.2,

	4-(2-oxo-2-

dione 22 Entry for the Table of Contents

  , 21.1;LR-MS: [M] + (C 16 H 12 O 4 ) m/z th. = 268, m/z found 268. ((Please choose one layout.))

	Layout 1:
	((Text for Table of Contents -max. 350
	characters; not the same text as the
	Abstract))
	Layout 2:
	The ruthenium catalyzed synthesis of	A series of diketones have been prepared	Ruthenium Catalyzed Synthesis of 1,2-
	1,2-diketones by oxidation of alkynes	in good yields from electron rich alkynes	diketones from Alkynes
	with sodium hypochlorite has been	whereas electron poor alkynes led to
	investigated. The reaction operates under	lower yields.	Keywords: Catalysis / Oxidation /
	environmentally friendly conditions of		Ruthenium / 1,2-diketones / alkynes
	oxidant, solvent and temperature.

1-phenylhexane-1,2-Oxidation of alkynes Y. Miao, A. Dupé, C. Bruneau,* C. Fischmeister* …….... Page No. -Page No.

Acknowledgments

The authors are grateful to the CNRS and the Ministère de l'Enseignement Supérieur et de la Recherche for support. We thank the Fondation Rennes 1 for a grant to Y. M. The authors also thank ADEME (Agence de l'Environnement et de la Maîtrise de l'Energie) and Région Bretagne for a PhD grant to AD.


Georges Randrianaina
email: georges-aaron.randrianaina@irisa.fr

Aaron

Incremental Build of Linux Kernel Configurations

Keywords: Linux Kernel, Highly Configurable System, Build Systems, Incremental Build

Building software is a crucial task to compile, test, and deploy software systems while continuously ensuring quality. The Linux Kernel is the most configurable and complex system with more than 15, 000 features. To speed up the building of such a large configuration set, and in contrast to the common workflow relying on only building clean configurations, we propose to incrementally build them.

Initial results do not provide any optimal order to incrementally build configurations due to a high distance between them. However, we show it is possible to control the configurations generation process: reusing commonality can save up to 66% of build time compared to only clean builds.

Introduction

The Linux kernel offers over 15, 000 features making it the most configurable and complex system. Indeed, the Linux Kernel is highly configurable: users can either enable -as an integrated feature or an external loadable module -or disable features and combine them to create a configuration [START_REF] Apel | Feature-Oriented Software Product Lines: Concepts and Implementation[END_REF]. The set of all possible configurations is called configuration space.

Problem. If each of these 15, 000 features could be enabled or disabled to obtain a valid configuration, the size of the configuration space would be 2 15000 . Logical constraints among features reduce this number but the configuration space remains huge. Thus building Linux configurations is crucial to test, deploy and learn from its non-functional properties for optimization or tuning. As stated by Greg Kroah-Hartman, Linux maintainer, at FOSDEM'10, "The Linux Kernel does not have a test suite[. . . ] for hardware interaction [. . . ] The best thing you can ever do for us is: you just build the Kernel and tell us if you have a problem. That is our QA cycle. " Building a Linux configuration running Make [START_REF] Feldman | Make -a program for maintaining computer programs[END_REF] takes on average nine minutes [START_REF] Acher | Learning From Thousands of Build Failures of Linux Kernel Configurations[END_REF]. Therefore, building a large amount of configurations is time and CPU consuming (about a week to build only 1000 configurations). Even though the goal is not to cover the entire configuration space, we aim to explore the combination of most common options.

Approach. We propose an approach to investigate the incremental build of configurations: rather than independently building each configuration and cleaning the build artefacts between each build, a configuration can instead be incrementally built from an existing and already completed configuration build. The idea is to reuse artefacts of previous configurations builds, hence saving some computations, resources, and time. Behind this idea, the real question is to quantify how much and where we can gain or lose compared to a more conventional build (in addition to already existing techniques such as distributed build). This approach has risks: an incremental build might not work or might be incorrect compared to a conventional build, for example the build system might "forget" to recompile some files. Another unknown remains about the strategy to schedule the incremental build of configurations. Given a set of configurations, numerous possible orderings exist, possibly with different effects on correctness and overall build cost (e.g., CPU time). Does incremental build pay off whatever the ordering and the distance among configurations? Is it worth finding an optimal ordering?

Incremental build

We present in this section our approaches that contribute to the incremental build of Linux configurations.

Ordering of random configurations. We address a first scenario of incremental build of configurations. Given a set of configurations (such as multiple Linux default configurations) we need to find an order to incrementally build them such that this outperforms the overall build time of only clean builds. To this end, we propose to incrementally build every pair of the set and if the incremental build outperforms clean build we then investigate the build artefact to understand the reasons why incremental build is effective and how to use it to order the set.

Configuration generation. In this scenario, starting from an initial configuration, we generate a set of configurations in which incremental build is guaranteed to outperform clean builds. To determine before compilation which files will be compiled if an option is enabled/disabled, we build a dependency graph (DG) between options according to their implementation at file level. If two options are implemented in the same file, an edge in the DG links them. This representation can over approximate the number of files to recompile when an option is modified in the configuration. Then the options that trigger fewer files to (re)compile are selected to be added/removed in the new configurations. We add them progressively to increase diversity by small increments, instead of building from scratch every configuration.

Incremental build correctness. An incremental build is correct if it is "identical" to a clean build. Here we suggest two criteria: the symbols and the size of the produced Linux binary vmlinux. If they are identical for both incremental and clean builds, the incremental build process is considered safe.

Preliminary results

Ordering of random configurations. We ran the experiment with two batches of 20 random configurations 1 of Linux. We could not find any pair of configurations in which incremental build was faster than clean build. After investigation, we found out that there was too much difference between two randomly generated configurations, with up to a thousand options added or removed. In addition, the strategies of the build system (Make) can also fail to reuse files and do redundant builds (see, e.g., [START_REF] Zhang | Abc: Accelerated building of c/c++ projects[END_REF]).

Configuration generation. We picked a random configuration and built it from scratch. Then we generated 9 configurations from it with the technique described in Section 2 using the DG. The number of different options between each generated configuration and the original varies from 7 to 183. Total CPU time using only clean builds was 4864 seconds, whereas total CPU time relying on one clean build of the initial configuration then incremental builds of the others was 1649 seconds, a gain of approximately 66% of build time.

Incremental build's correctness. For all our experiments, correctness holds according to our criteria.

Future work

A priori knowledge for ordering configurations. As shown in Section 3, the brute force strategy of picking random configurations does not bring benefits for Linux because of high differences among these random configurations. We plan to develop techniques to infer knowledge directly from the build system [START_REF] Dietrich | A robust approach for variability extraction from the linux build system[END_REF][START_REF] Tartler | Feature consistency in compile-time-configurable system software: Facing the linux 10,000 feature problem[END_REF], so as to deduce similarities among possible configurations and determine an a priori order to incrementally build them.

Automatic generation of configurations. We plan to improve our configurations mutations to add/remove more options (beyond 183). We aim to automatize the whole process to explore the configuration space while effectively using incremental build. We plan to investigate how to bring the technique to continuous integration platforms, improving our builds with distribution and even more caching. 1

Generated using randconfig 5 Related work

Large scale build infrastructures for Linux [START_REF]Intel, 0-day, an automated linux kernel test service[END_REF][START_REF] Kernelci | a community-led test system focused on the upstream linux kernel[END_REF][START_REF] Martin | Transfer learning across variants and versions: The case of linux kernel size[END_REF] exist that build hundreds of Linux configurations per day. Nevertheless, they only perform clean builds.

Many works exist about build systems [START_REF] Bazel | A fast, scalable, multi-language and extensible build system[END_REF][START_REF] Cao | Forecasting the duration of incremental build jobs[END_REF][START_REF] Erdweg | A sound and optimal incremental build system with dynamic dependencies[END_REF][START_REF] Feldman | Make -a program for maintaining computer programs[END_REF][START_REF] Hammer | Incremental computation with names[END_REF][START_REF] Konat | Scalable incremental building with dynamic task dependencies[END_REF][START_REF]Correct, efficient, and tailored: The future of build systems[END_REF][START_REF] Mitchell | Shake before building[END_REF][START_REF] Schwanke | Smarter recompilation[END_REF][START_REF] Tichy | Smart recompilation[END_REF] but focus on code changes through the evolution of software (e.g., commits) rather than configurations. Maudoux et al. [START_REF] Maudoux | Bringing incremental builds to continuous integration[END_REF] show that incremental build could speed up builds of continuous integration (CI), and Gallaba et al. [START_REF] Gallaba | Accelerating continuous integration by caching environments and inferring dependencies[END_REF] that caching can accelerate CI. An open issue is to adapt these techniques over distant software configurations that may have very different impacts on the files to build.

The Variability and Software Product Lines (SPL) community develops numerous methods and techniques to manage a family of variants (or products). Formal methods and program analysis can identify some classes of configuration defects [START_REF] Classen | Featured Transition Systems: Foundations for Verifying Variability-Intensive Systems and Their to LTL Model Checking[END_REF][START_REF] Thüm | A classification and survey of analysis strategies for software product lines[END_REF], leading to variability-aware testing approaches (e.g., [START_REF] Fischer | Testing of highly configurable cyber-physical systems -a multiple case study[END_REF][START_REF] Kastner | Type-checking software product lines-a formal approach[END_REF][START_REF] Kenner | Typechef: Toward type checking #ifdef variability in c[END_REF][START_REF] Kim | Reducing combinatorics in testing product lines[END_REF][START_REF] Kim | Splat: lightweight dynamic analysis for reducing combinatorics in testing configurable systems -esec/fse '13[END_REF][START_REF] Lima | Learning-based prioritization of test cases in continuous integration of highly-configurable software[END_REF][START_REF] Nguyen | Exploring variabilityaware execution for testing plugin-based web applications[END_REF][START_REF] Reisner | Using symbolic evaluation to understand behavior in configurable software systems[END_REF][START_REF] Shi | Integration Testing of Software Product Lines Using Compositional Symbolic Execution[END_REF][START_REF] Von Rhein | Variability-aware static analysis at scale: An empirical study[END_REF]). Static analysis and notably type-checking have been used to find bugs in configurable software and can scale to very large code bases such as the Linux Kernel [START_REF] Kastner | Type-checking software product lines-a formal approach[END_REF][START_REF] Kenner | Typechef: Toward type checking #ifdef variability in c[END_REF][START_REF] Von Rhein | Variability-aware static analysis at scale: An empirical study[END_REF]. Though variability-aware analysis is relevant in many engineering contexts, our interest differs and consists in studying the practice of concretely building a sample of (possibly distant and diverse) configurations with an unexplored approach -incremental build. Sampling configurations is subject to intensive research [START_REF] Pereira | Sampling effect on performance prediction of configurable systems: A case study[END_REF][START_REF] Jamshidi | Learning to sample: exploiting similarities across environments to learn performance models for configurable systems[END_REF][START_REF] Souto | Balancing soundness and efficiency for practical testing of configurable systems[END_REF][START_REF] Thüm | A classification and survey of analysis strategies for software product lines[END_REF]; incremental build brings new challenges. We are unaware of studies that consider or apply incremental build of configurations.

Conclusion

We presented our approach that consists in bridging incremental build with software configurations. Results of preliminary experiments over the Linux Kernel show that incremental build can reduce the cost of building (e.g., a gain of 66% when controlling the generation of configurations). We intend to test this approach on broader software projects, beyond Linux. Yet several challenges remain, related to the diversity of configurations and the ordering of incremental builds. Many software projects face the problem of building multiple configurations and we encourage the software engineering community to more widely explore the potential of incremental build (e.g., combination with parallel or distributed build).

Acknowledgments

I would like to thank my PhD advisors: Mathieu Acher, Djamel Eddine Khelladi and Olivier Zendra.