Jed Kraiem
email: jed.kraiem@insa-lyon.fr

O Nichiporuk

Pierre Papet

J.-F Lelièvre

Alain Fave

Anne Kaminski

Erwann Fourmond

J-P Boyeaux

P-J Ribeyron
email: ribeyronpj@chartreuse.cea.fr

A Laugier

Interdigitated

J-F Lelievre

M Lemiti

Interdigitated Back Contacts Solar Cells on Transferred Si-Thin Film Epitaxially Grown on Porous Silicon

Keywords: Layer Transfer Process, Silicon Thin Film, Rear Contacts Cell

Introduction

One alternative to the conventional solar cells fabricated on bulk material is the realization of silicon thin film solar cells by epitaxial layer transfer process (LTP). Since few years, this approach appears to be one attractive way to realize cheap and efficient solar cells [1,2,3]. Efficiency up to 16.6% [4] was reported for solar cells realized on transferred epitaxial layer with conventional structure (both side's contacts, phosphorous diffused p-n junction). However, the high quality of epitaxial layer allows considering interdigitated back contacts (IBC) cell structure [5]. Actually, IBC structure which has recently received a lot of attention, mainly because of the successful development of such a technology by SunPower [START_REF] Mulligan | 19 th EPVSEC[END_REF], offers multiple advantages comparative to conventional both sides contacts technology: higher short-circuit current (no shading loss), low serial resistance and simplified module assembling.

The aim of this paper is to present this novel approach to silicon thin film solar cells technology. For the first time interdigitated back contacts solar cells are realized on epitaxial thin film transferred from the substrate thanks to a sacrificial layer. All the process steps are described in order to demonstrate that this technology suits well to the epitaxial layer transfer process.

Layer Transfer Process

Layer Transfer Process using porous silicon as a weakened layer is a very promising method to realize thin film silicon solar cells. However, there are 3 critical steps: Epitaxial growth of high crystal quality Si film, Control and repeatability of the transfer, and Re-use of the initial substrate limiting Si consumption.

Porous Silicon

Porous silicon is formed by standard electrochemical etching of (100) silicon wafers doped with boron (ρ=0.008Ωcm) in HF solutions. A double phase etching process generates two superposed PS layers: a 1µm-thick top layer with a low porosity (23%) allowing high quality crystal growth, and a 0.5µm-thick buried layer with a high porosity (70%) for the further detachment of the epilayer.

Annealing and Silicon Epitaxy

Prior to epitaxy, porous silicon is annealed under hydrogen at 1100°C for 10 minutes. During this step, porous silicon restructuration leads to a densification of the surface. In the same time reorganization of the bottom layer leads to a fragilisation allowing subsequent detachment. Then epitaxial growth by VPE leads to a 70µm thick epilayer with a 1.10 16 cm -3 doping level. Structural and electrical characterizations showed the high crystal quality of the epilayer [START_REF] Kraiem | 31th IEEE Photovoltaic Specialists Conference and Exhibition[END_REF].

Cell Process (Part 1)

For IBC cells, we use a simplified technological process. A typical fabrication sequence might be: n + diffusion on the whole surface using solid source, etch a finger pattern in the n + region and into the underlying silicon, Al deposition in the etched finger pattern and contacts annealing at 600°C for ohmic contact and BSF formation. The last step is deposition of the emitter contacts (Ti-Pd-Ag) aligned to Al contact grid.

Transfer

Then, epitaxial layer is transferred onto inexpensive substrate by an innovative method which allows a perfect control of the detachment and his repeatability (to be patented).

Cell Process (Part 2)

Finally, the residual porous silicon presents on the detached side is removed by chemical etching. Then texturation of the front side is realized using tetra-methyl ammonium hydroxide (TMAH) before deposition of a 75nm thick SiN antireflective coating. A weighted reflectance below 3% is achieved [START_REF] Papet | al. 14 th Inter[END_REF].

Substrate Re-use

Re-use of the initial substrate starts also by removing the residual porous silicon caused by the separation step. We optimize this step in order to minimize surface roughness and Si consumption. After testing several chemical etchings, RMS surface roughness below 3nm was obtained, 6 consecutives transfers using the same wafer were achieved and Si consumption was only 5.2µm per cycle [START_REF] Kraiem | al. 14 th Inter[END_REF].

Results and Discussion

For the presented cell below, we used a simplified ELIT process. Cell fabrication was directly realized on detached 70µm-thick epilayer. Several IBC cells were realized on the same epitaxial film and were then separated by sawing. The results from the best cell are summarized here.

Dark I(V)

We have extracted the parameters of the dark I(V) characteristics of the best cell using the one diode model (Fig. 2). We observe that the shunt resistance is not as high as expected. One possibility to explain this weak value is the leakage current caused by the sawing damages at the cell perimeter. In the same time, serial resistance is relatively high for IBC cell. Optimization of the contact grid geometry and the contacts firing should improve this parameter. Under an AM1.5 global spectrum, the best cell was found to be 7.7% efficient at one sun, with a FF=0.53, a Jsc=25mA.cm² and a Voc=557mV.

In order to estimate the potential of IBC cell on epilayer, SunsV oc system was used. The advantage of the Suns V oc measurement is that it gives the solar cell current voltage curve without the effects of series resistance [START_REF] Sinton | NREL 9th Workshop on Crystalline Silicon Solar Cells and Materials and Processes[END_REF]. Cell efficiency higher than 10% with a fill factor of 0.74 can be obtained.

With optimizing the cell architecture and contacts ohmicity higher efficiencies on transferred IBC cells can be reached.

Fig.3 Illuminated and Suns Voc current-voltage curves of IBC solar cells on epilayer 4 Conclusions

Finally for the very first time, we show that it is possible to fabricated interdigitated back contacts solar cells on transferred epitaxial layer and we demonstrate this technology suits well to the layer transfer process. In our preliminary experiments a 7.7 % efficiency solar cell was obtained in a 70 µm thin active layer. The cell so far shows high serial resistance due to non optimized cell architecture. Given the scope of possible improvements (higher quality emitter and optimized contacts geometry) we are confident that high efficiencies can be obtained with such technique.

Fig. 1

 1 Fig.1 Schematic of the ELIT process

Fig. 2

 2 Fig.2 Dark current-voltage curve of IBC solar cell on epilayer3.2 Illuminated I(V) and Suns V oc

Fig. 3

 3 Fig.3 represents illuminated I(V) characteristic and Suns-V oc pseudo-I(V).Under an AM1.5 global spectrum, the best cell was found to be 7.7% efficient at one sun, with a FF=0.53, a Jsc=25mA.cm² and a Voc=557mV.In order to estimate the potential of IBC cell on epilayer, SunsV oc system was used. The advantage of the Suns V oc measurement is that it gives the solar cell current voltage curve without the effects of series resistance[START_REF] Sinton | NREL 9th Workshop on Crystalline Silicon Solar Cells and Materials and Processes[END_REF]. Cell efficiency


ASYMMETRIC CATALYSIS

Selecting one out of six stereoisomers

The design of an original molecular architecture featuring an unusual sterically congested C(sp 2 )-C(sp 3 ) stereogenic axis with six high rotational barriers results in the formation of six stereoisomers. The configuration of this axis can be controlled by transition metal catalysis and one stereoisomer can be produced selectively.

Damien Bonne and Jean Rodriguez I n 1874, Le Bel 1 and van 't Hoff 2 independently found that the four valencies of the carbon atom are directed towards the vertices of an atom-centred tetrahedron. This discovery laid the foundations of the theory of molecular structure. The now-very-popular Le Bel-Van 't Hoff rule of stereochemistry is taught to undergraduate students. This rule states that the total number of stereoisomers of a molecule with no internal plane of symmetry is 2 n , where n represents the number of stereogenic elements 3 . Therefore, molecules containing one stereogenic element -such as a stereocentre or a less-encountered axis, plane or helix -can exist as two stereoisomers which are, in this case, enantiomers of opposite configuration.

Controlling the configuration of one stereogenic element at a time is a well-mastered task [START_REF]Asymmetric Catalysis on Industrial scale: Challenges, Approaches and Solutions 2nd edn[END_REF][START_REF] Cheng | [END_REF] , thanks to the development of enantioselective catalysisinteractions between a chiral catalyst and the substrates produce two diastereomeric transition states, with the less energetic one being favoured over the other one. This leads to the formation of one major enantiomer. Now, writing in Nature Catalysis, Christof Sparr and co-workers have developed an enantioselective rhodium-catalysed [2+2+2]-cyclotrimerization leading to the formation of one out of six stereoisomers with up to 0:0:2:98:0:0 stereocontrol 6 . This was made possible thanks to the design of chiral 9-aryltriptycene derivatives featuring an unusual C(sp 2 )-C(sp 3 ) stereogenic axis that offers six high rotational barriers. Pioneering observations of slowed rotation around a C(sp 2 )-C(sp 3 ) stereogenic axis were observed by Nakamura and Ōki in 1975 using dynamic nuclear magnetic resonance 7 and were also found to be present in some interesting families of natural products 8 . In the work reported in Nature Catalysis, the designed, intriguing axially chiral molecule exists as several isolable configurations resulting from the sterically congested C(sp 2 )-C(sp 3 ) stereogenic axis triggering unusually high rotational barriers to go from one stereoisomer to another.

The researchers started their work with feasibility studies in the racemic series from a substrate lacking the ketone function (highlighted in pink in Fig. 1). In this case, the expected formation of the six stereoisomers as a mixture of three couples of racemic diastereomers was observed and they were identified as synperiplanar (sp), clinal (c) and antiperiplanar (ap) with respect to the relative position between the ketone function and the N-R 2 group in a diastereomeric ratio of 1:1.3:1.5, respectively. All six stereoisomers could be resolved by high-performance liquid chromatography (HPLC) on a chiral stationary phase. Slow interconversion between some of them indicated that some of the rotational barriers were not high enough to prevent the rotation. Interestingly, the enantiomerization of the antiperiplanar (ap) isomers, which required the bulky adamantyl group (Ad) to go through the inner imide's carbonyl group, was not observed. This suggests that the rotational barrier was high enough to prevent rotation in this case.

With the ketone functional group (highlighted in pink in Fig. 1), all rotational barriers increased above 110 kJ mol -1 , preventing interconversion between the stereoisomers at room temperature. This substrate was chosen for the optimization of the enantioselective catalyst-controlled [2+2+2]-cyclotrimerization reaction. Several chiral ligands were used, which allowed identification of the bisphosphine (S a )-xyl-SDP as the best one and gave the desired product in good yield (75%) and with excellent stereoselectivity. Only antiperiplanar (ap) pair of enantiomers was formed, with high enantioselectivity for the (+)-ap enantiomer (0:0:7:93:0:0).

The scope was then investigated and the authors found an important effect of the R 2 group on the enantioselectivity, which was superior for electron-poor aryl groups. The influence of the nature of the tether moiety between both triple bonds (R 1 group, Fig. 1) showed that both a N-tosyl group and a diethyl malonate linkage were compatible and gave good yields and stereoselectivities. An additional stereogenic C-N bond could be installed in the product when R 2 was a bulky ortho-ethoxyphenyl group, leading to a 2:1 mixture of rapidly interconverting C-N atropisomers, due to a low rotational barrier of this stereogenic bond (70 kJ mol -1 ).

Finally, the stereodivergent nature of this transformation was demonstrated 9 : the use of a chiral N-heterocyclic carbene (NHC) ligand led to selective formation of clinal (c) isomers over the antiperiplanar (ap) isomers (d.r. = 83:17), with high enantioselectivity (e.r. = 94:6). Here also, formation of the synperiplanar (sp) isomers was not observed. Hence, by careful selection of either a chiral bisphosphine or an NHC ligand, four of the six stereoisomers are accessible, each of them with good enantioselectivity.

The methodology developed by Sparr's group represents a striking realization in catalyst-controlled reactions achieving control over higher-order stereogenicity.

They have showed that the ingenious design of a molecule and its stereogenic element, a rare sterically congested C(sp 2 )-C(sp 3 ) bond, can lead to the existence of more than two stereoisomers, six in this case. This is possible because the resulting multiple conformations become multiple configurations due to the different high rotational barriers. In addition, stereodivergent synthesis of four of the six stereoisomers was accomplished by switching the catalyst. Probably for steric reasons, only the synperiplanar (sp) isomers could not be obtained selectively. This challenge could be solved using catalyst design, which would undeniably constitute a major achievement for stereodivergent transformations.

We do believe that this emerging area of research is opening unforeseen possibilities and will have a deep impact on future developments in stereoselective catalysis. This work represents an important milestone in both atropisomerism and stereoselective catalysis, and should trigger new ideas and realizations in many research groups. ❐ Damien Bonne ✉ and Jean Rodriguez ✉ Aix-Marseille Université, CNRS, Centrale Marseille, iSm2, Marseille, France. ✉ e-mail: damien.bonne@univ-amu.fr; jean.

rodriguez@univ-amu.fr

Published online: 21 June 2021 https://doi.org/10.1038/s41929-021-00639-5

Fig. 1 |

 1 Fig.1| Catalyst control over higher-order stereogenicity. The use of a chiral rhodium complex as catalyst in a [2+2+2]-cyclotrimerization reaction allows the formation of one major cycloadduct among the six possible stereoisomers.

Competing interests

The authors declare no competing interests.


Bohdan Biletskyi

Pierre Colonna

´vin Ke

Jean-Luc Masson

Laurent Parrain

Commeiras

Dr Gae ¨lle Chouraqui
email: gaelle.chouraqui@univ-amu.fr

Bohdan Biletskyi Bohdan

Prof Laurent

Ke ´vin Masson

Kevin Masson

Dr Jean-Luc Parrain

Jean-Paul Quintard

Laurent Commeiras

He

Sir Jack E Baldwin

James H Rigby

Small rings in the bigger picture: ring expansion of three-and four-membered rings to access larger all-carbon cyclic systems

The release of the inherent ring strain of cyclobutane and cyclopropane derivatives allows a rapid buildup of molecular complexity. This review highlights the state-of-the-art of the ring expansions of threeand four-membered cycles and is organised by types of reactions with emphasis on the reaction mechanisms. Selected examples are discussed to illustrate the synthetic potential of this elegant synthetic tool.

Introduction

The importance of step economy towards the construction of molecular diversity is still a challenge that the synthetic organic chemists' community is eager to take up. 1 On the other hand, a major advantage of small rings is their inherent ring strain 2 and, consequently, their high reactivity. The reported values of the strain energy, viz. 27.5 kcal mol À1 for cyclopropane and 26.5 kcal mol À1 for cyclobutane (0 kcal mol À1 for the benchmark cyclohexane), clearly set the stage for ring-opening through strain relief. 3 This release of ring tension allows for a scalable, rapid and controlled synthetic access to the expected target molecules. [START_REF] Carson | For reviews on cyclopropane and cyclobutane strategies in natural product synthesis, see for instance[END_REF] In particular, these methods are applicable to propose new fragments in ''Diversity Oriented Synthesis (DOS)'' of fine chemicals and materials. [START_REF] Galloway | [END_REF] This review aims to provide a recent account on the ring expansion of cyclobutyl and cyclopropyl derivatives to access larger membered all-carbon rings. Thanks to their inherent ring strain, small rings represent a valuable three-or fouratoms building element in the search to reach molecular complexity in an atom economical manner. Rearrangements,6 in that perspective, are an opportunity for small size rings to participate in fascinating chemical transformations. In addition, rearrangements of small rings are not only ruled by stereoelectronic considerations but also, by steric effects. For those reasons, high stereoselectivity often arise from such approaches. Although the ring enlargement of cyclopropyl and cyclobutyl derivatives was covered in different reviews, none was available on the recent progress made on this specific topic. For instance, Njardarson disclosed in 2013, the metalcatalysed ring enlargement of three-and four-membered rings. 7 In 2011, Cramer gave an account on cyclobutanes in catalysis. 8 The ring expansion strategy as a key step in the total synthesis of natural products has also been covered several times but it is either old [START_REF] Carson | For reviews on cyclopropane and cyclobutane strategies in natural product synthesis, see for instance[END_REF] or quite specific to a particular molecular species (i.e. cyclopropanols). 9 Cyclobutanols and cyclopropanols, as a matter of fact, have been the focus of very recent attention. 9,10 The purpose of this review is to give an overview of the progress made since 2012 and collected up until December 2020.

Ring expansion of small carbocyclic systems can be classified into three main groups of rearrangements (Scheme 1), and the following discussion was structured according to these three types of reactions: [START_REF] Hesse | Ring enlargement in Organic Synthesis[END_REF] -Group 1: carbon(s) insertion through opening of a bicyclic system, instigated by functional groups decorating the ring, -Group 2: carbon(s) insertion through migration to an exocyclic group, -Group 3: electrocyclic and sigmatropic reactions.

We wish to critically discuss the scope, applications, mechanisms and the potential for future development of the title species. It is not intended to give here, a comprehensive inventory, but provide the reader with a multifaceted and global vision. We apologise to any author whose paper is not listed here but could be.

Group 1: carbon(s) insertion through opening of a bicyclic system

This first part is based on solid and well-established methodologies such as fragmentation, retro-aldol, de Mayo, or 1,2elimination reactions. Accordingly, the resulting ring cleavage of fused bicyclic scaffolds depicted here, and containing threeor four-carbon atom cycles, leads to the corresponding allcarbon four-to twelve-membered ones. These recognised transformations [START_REF] Hesse | Ring enlargement in Organic Synthesis[END_REF] are still relevant since many of them are used for the synthesis of natural product skeletons, therefore showing the indisputable synthetic potential of this kind of strategy. Herein, we decided to focus on contributions about the synthesis of natural molecules and privileged structure motifs found in natural products and/or biologically relevant targets. The different articles have been classified according to the resulting ring-size and we chose to first highlight the challenging task of performing a total synthesis of natural products.

In 2016, Fox and co-workers reported the first enantioselective total synthesis of piperarborenine B (1) in ten steps, with an 8% overall yield and 92% ee (Scheme 2). [START_REF] Panish | [END_REF] The key step involved a one pot Rh(II)-catalysed enantioselective bicyclobutanation [START_REF] Qin | The enantioselective bicyclobutanation was independently reported by Davies and Fox[END_REF] /Cu(I)-catalysed homoconjugate addition of a-cynnamyl-a-diazoesters sequence. The enantioselective decomposition of the 2-diazo-5-arylpent-4-enoate 2 into the corresponding bicyclo[1.1.0]butane 3 at À78 1C was followed by a cuprate-mediated ring opening. A subsequent kinetic protonation in presence of a bulky proton source (BHT), finally set the relative stereochemistry on the four-membered ring. The desired diastereomer 4 was thus produced in a 4 : 1 ratio. The cyclobutane was obtained in 69% yield and 92% ee. The bicyclo[1.1.0]butane ring system is a fascinating moiety since it is probably the most strained bicyclic compound (66.3 kcal mol À1 ). 14 As a result of its highly puckered conformation, both nucleophiles and electrophiles can engage in reaction with bicyclo[1.1.0]butanes. The nucleophilic addition of the Grignard reagent occurs along the axis of the 2p-orbitals forming the central bent s-bond, thus explaining the relative diastereoselectivity observed (see nucleophilic approach Scheme 2).

Kaurane diterpenoids are integral parts of terpenoid natural products and their attractive structural diversity associated with a wide range of bioactivities have evoked a great deal of interest in the synthetic community. 15 A regioselective fragmentation of overbred intermediates [START_REF] Hoffmann | Term introduced by Hoffman in 2009 describing intermediates in a synthetic route that contain one or more C-C bonds that will break to get the target product[END_REF] was reported by Baran's group for the synthesis of ent-kaurane and beyerane diterpenoids. [START_REF] Cherney | [END_REF] Gratifyingly, starting from an embedded polycyclic protected cyclopropanediol derivative 5 and by simple treatment with acyl chloride in methanol at low temperature, the preferential formation of the desired kinetic product 6 was obtained in 79% (Scheme 3). The undesired thermodynamic adduct 7 was also isolated but in much lower yield 11% (7.2 : 1 ratio). Ultimately, this compound set the stage for the final transformation toward the racemic natural product (AE)-steviol (8). The latter was reached in seventeen steps from geranyl acetate in 2.6% overall yield. The embedded starting structure 5 is the key element enabling the regio-and stereoselective construction of the desired polycyclic core of (AE)-steviol (8).

Very recently, Nelson disclosed an impressive work on the total synthesis of (AE)-vibralactone (9). 18 The target was obtained in five steps only (4.3% overall yield). This approach is completely protecting-group-free and the five membered ring is elegantly installed thanks to the fragmentation of a strained [2.1.0] housane structure (Scheme 4). The base-mediated ringexpansion was performed on compound 10, in presence of 1.5 equivalent of DBU in benzene at 75 1C and for 18 hours. The regioselective cyclopropane ring cleavage furnished the expected cyclopentene 11 in 69% yield, in an atomeconomical fashion. The selectivity of the ring opening was explained by the kinetic protonation of the allyl anion 12 the furthest away from the sterically congested quaternary centre. Simple reduction of the ester 11 to the corresponding alcohol in presence of DIBAL-H, gratifyingly delivered the natural product (9). Synthesizing a strained intermediate 10 was totally worth the effort, since it is the shortest reported synthesis of (AE)-vibralactone (9) to date. 19 Another classical reaction has been utilised to access medium-size carbocyclic systems of natural products on number of occasions. 20 It relies on the well-known Saegusa one-carbon ring expansion protocol 21 of [4.1.0] bicyclic structures (Scheme 5). Accordingly, the corresponding sevenmembered ring found in the intricated unusual structure of echinopine B ( 13) 22 and the cytotoxic terpenoid (À)-hortonone C ( 14) 23 was satisfyingly delivered thanks to this approach. Parented examples were also described in the literature and allowed the total synthesis of (AE)-schindilactone A ( 15) 24 (eqn (1)) and rameswaralide ( 16) (eqn ( 2)) (Scheme 6). 25 Respectively, silver salts were used instead of iron or a radical pathway undertaken, on a necessary brominated cyclopropane derivative. The overall process provided an elegant and facile procedure for the conversion of six-membered rings into the one carbon ring-expanded enones and proved useful in the synthesis of natural products containing such ring systems. These last four examples brought closure to the section devoted to the total synthesis of natural products and it is worth noting that, carbocyclic skeletons from four-to seven-membered rings could be reached. Next, a comprehensive inventory of the different approaches to relevant targets, with interesting structural complexity and as a potential mean to explore the chemical space in drug design is given.

Cyclic scaffolds featuring benzo-fused-(6,7)-bicyclic moieties are structural motifs found in many biologically active natural and unnatural molecules. 26 Carbon insertion through opening of a bicyclic system is one of the methods allowing the construction of these challenging structures. 27 These transformations enable the synthesis of molecular scaffolds with welldefined three-dimensional arrangement in a straightforward manner. 28 For instance, Meng and Cao uncovered a goldand triflic acid co-catalysed [4+2]/ring expansion domino cascade (Scheme 7). 29 Reaction of ortho-alkynylaldehyde 17 with cyclopropenes 18 in presence of 10 mol% gold catalyst and 0.5 equivalent of TfOH in dioxane at 90 1C, provided an efficient access to the corresponding benzo [7]annulene 19 in good yields, with an excellent diastereoselectivity and a complete Z-selectivity of the exocyclic olefin. The proposed mechanism suggested that, a gold-mediated 6-endo-dig cyclisation by the oxygen atom could then be followed by an endo-intermolecular Diels-Alder cycloaddition reaction with the cyclopropene 18, playing the role of the dienophile. Next a protodeauration on the tricyclic intermediate 20 and an elimination step, could afford the [4.5.0] bicyclic derivative 19. Due to unfavourable entropic factors and transannular interactions, sevenmembered carbocyclic rings are relatively more difficult to synthesize than their five-or six-counterparts. Consequently, developing strategies to reach this kind of platforms is always needed. On the other hand, bridged ring systems are highly valued as they feature key complexity descriptors 30 and the imparted ring strain renders their synthesis more difficult than the fused ones.

In 2015, Qu and co-workers 31 reported an isolated example of bridged ring system construction via the ring expansion of a cyclopropyl bicyclic derivative. The rearrangement of the tricyclic structure 21 occurred in a boiling 9 : 1 mixture of water and 1,4-dioxane and allowed the construction of the [4.3.1] bicyclic structure 22 albeit as a minor product and therefore in low yield (12%) (Scheme 8). The major compound 23 came from the non-fused C-C cyclopropyl bond cleavage, via the more stable tertiary carbocation, and was isolated in 62% yield. It is noteworthy to mention that such a strategy, also allowed the formation of fused eight -24 and nine-membered carbocyclic rings 25, which are even more complicated to obtain than the seven one. The medium-size rings (from eight-to elevenmembered rings) synthesis represent a real synthetic challenge for organic chemists due to the high ring strain. [START_REF]For selected reviews on the synthesis of medium-size rings, see[END_REF] The release of small ring strain via their expansion, once again, proved beneficial to overcome the unfavourable entropic and enthalpic factors inherent to the formation of higher order cycloadducts.

Gui also studied the cyclopropane scission of tricyclo [4.4.1.0 1,6 ]undecane, for the unified synthesis of ten cyclocitrinols. 33 After in-depth studies, the authors established a cascade rearrangement on a derivative of pregnenolone 26, an endogenous steroid hormone (Scheme 9). When the latter was submitted to m-CPBA the corresponding sulfoxide was oxidised to sulfone and underwent an elimination step. After the supposed cyclopropyl intermediate 27 formation, the ring expansion would Scheme 6 Approach to schindilactone A (15) and rameswaralide (16). lead to the cycloheptadiene 28. A careful examination of the base used in such process allowed the regioselective installation of the last double bond at the C1-C10 bond. The desired abeo-steroid 29 was obtained on a gram scale in 54% yield (over two steps) and with 8.2 : 1 regioselectivity. Thereafter, the key intermediate 30 was utilised to reach ten cyclocitrinols in ten to twelve steps from pregnenolone. We already established the difficulty to access bridged ring system, owing to ring strain of this kind of scaffold. Here, the authors added an additional challenge since they even managed to control atropisomerism via point-to-planar chirality transfer.

Another interesting application of the ring expansion of four-membered rings this time, has been reported and allows the formation of cyclohepta [b]indoles, a structure motif displaying a broad spectrum of biological activities. 34 Yang and Deng reported a one-pot enantioselective sequence starting with an organocatalysed Michael addition of cyclobutanone 31 onto 2-nitrovinylindole 32 (Scheme 10). 35 This reaction led to intermediate 33 and epi-33 which, upon action of boron trifluoride etherate Lewis acid, underwent a cyclisation to the five-membered ring. The latter could spontaneously perform a fragmentation and deliver the corresponding medium-size indolic systems in yields up to 84%, as a mixture of two diastereomers cis-and trans-34 respectively and with excellent enantioselectivities. The stereoselectivities have been rationalised: the diastereoselectivity could originate from the protonation step of the amide enolate and the enantioselectivity from the Michael addition step catalysed by a chiral bifunctional aminocatalyst. The authors not only demonstrated the broad substrate scope and the scalability of the process but also, the high synthetic potential of the obtained imbedded scaffolds.

Another approach to cyclohepta [b]indoles and other useful seven-and even eight-membered carbocyclic platforms, relies on an intramolecular alkyne-de Mayo reaction (Scheme 11). 36 A photochemically induced cascade process starting from 35 in a polar protic solvent provided the desired adduct 36 in excellent yields. The mechanism to the seven-membered ring presumably proceeds through the intermediate tricyclic cyclobutene cis-S 0 -37 via a retro-Mannich reaction.

As already stated, the formation of challenging larger ring systems can benefit from the strain release of small-size cyclic compounds. In 2016, Li and co-workers showed that the Scheme 10 Synthesis of medium-size indolic system (2016).

unstrained system 38, strictly under basic conditions, in a metal-free medium, and in presence of a cyclic keto ester 39, led to the corresponding eight-membered ring 40 in excellent yields (Scheme 12). 37 This transformation tolerated a range of different substituents both on the alkyne and/or the aromatic part of the molecule. A closer look at the suggested mechanism is necessary to understand why this example is part of this review. Michael addition of the enolate of 39 onto the keto alkyne 38 provided intermediate 41. The latter could undergo an intramolecular aldol reaction leading to the strained four-membered ring 42, which could spontaneously evolve to the desired all-carbon eight membered cycle 43. Overall, this protocol allowed an internal alkyne insertion into a C-C-s-bond of cyclic b -dicarbonyl compounds, starting from easily available starting materials and under mild reaction conditions. A new synthesis of cycloocta [b]chromene was thus delivered. [START_REF]For a ring expansion strategy towards cyclohepta[END_REF] Finally, an example stood out and was reported by Murakami. 39 The stereospecific construction of metacyclophanes with planar chirality was possible thanks to a two steps sequence starting from orthocyclophanes with central chirality. Cyclophanes are strained molecules playing an important role in supramolecular assembly, and that are also found in natural products and in some pharmaceuticals. 40 Consequently, stereoselective method to access such skeleton is of paramount importance. Exposure of benzocyclobutanol 44 to 2.5 mol% of rhodium catalyst in toluene at room temperature, in presence of a Michael acceptor (10 equiv.) furnished the ring expanded product 45 in 82% yield with central-to-planar chirality transfer (420 : 1) (Scheme 13).

The few examples presented above showed that the design and construction of building blocks, as integral part of natural products and/or biologically relevant structures, are still an important area of research. Total synthesis continues to be an exciting and inspirational field for organic chemists. 41 Potent methodologies based on strain-release driven transformations, were reported here, and allowed an access to complex molecular structures containing, for instance, bridged systems, fourmembered and medium-size rings.

Group 2: 1,2 atom migration

The 1,2-alkyl migration of one of the C-C bonds of small cyclic systems onto an adjacent electrophilic carbon centre, is another general method for the ring expansion to the corresponding four-and five-carbocyclic compounds. The driving force of this 1,2-atom migration usually comes from the relief of angle strain, torsional strain or steric crowding and, is driven by the presence of a tertiary alcohol (or an ether or even an amine) therefore generating a carbonyl group. Semipinacol and Tiffeneau-Demjanov methods meet these criteria and, to some extent, Wagner-Meerwein rearrangement can be associated to this kind of mechanism (Scheme 14).

Semipinacol rearrangement

The ring expansion of cyclopropanols and cyclobutanols have been repeatedly utilised in a well-known classical reaction, the Scheme 11 Approach to cyclohepta [b]indoles (2018).

Scheme 12 Synthesis of cycloocta [b]chromene (2016). semipinacol rearrangement. 42 This transformation takes advantage of the electron pushing effect of the hydroxyl group. Accordingly, last year, Natho et al. 10a gave an account on the recent progress made on the ring expansion of cyclobutanols. Le Bras and Muzart, 10b for their part, focused on the Pdcatalysed reactions of cyclopropanols and cyclobutanols. In 2019, Dai enumerated the different total syntheses using a cyclopropanol pathway. 9 Obviously, the development of scaffolds bearing these privileged moieties (cyclopropanols 43 and cyclobutanols) is still a topic of importance. The semipinacol rearrangement of the aforementioned species has therefore been quite covered and we refer the reader to the different reviews for further references. Consequently, this part is intended to provide an update overview for the transposition of cyclopropanols (since 2012) and to highlight the rearrangement of alkenyls cyclobutanols since 2019.

3.1.1. Semipinacol rearrangement of cyclopropanols. Goldcatalysed approaches are important for the semipinacol rearrangement of cyclopropanols. 44 This strategy gives access to cyclobutanes, a building block not only frequently present in natural products, 45 but also a precursor to more complex structures through ringopening, ring-expansion, and ring-contraction reactions. [START_REF] Carson | For reviews on cyclopropane and cyclobutane strategies in natural product synthesis, see for instance[END_REF]7,10 The cycloisomerisation of cyclopropylenynes and analogues initially developed by Echavarren and Toste, 46 has found application for instance, in the synthesis of the protoilludane core of russujaponol D ( 46) (Scheme 15). 47 When allenene 47 was submitted to a cationic gold catalyst, the corresponding (5,6,4)tricyclic structure 48 was obtained in 92% yield as a mixture of two regioisomers (2 : 1 48a : 48b). From a mechanistic point of view, this reaction could proceed through a 5-exo-trig cyclisation, triggered by a prior coordination of the gold catalyst to the allene 47. The carbocationic intermediate 49 could then undergo the semipinacol rearrangement to the four-membered ring 50. A Prins cyclisation, followed by an elimination and a subsequent protodemetallation could afford the observed tricyclic structures 48a and 48b. Another example relied on the enantioselective version of the Au-mediated rearrangement of cyclopropylenynes. 48 In presence of a chiral bis-(phosphine)-digold(I)catalyst, the corresponding cyclobutanones 51 were obtained in yields up to 94%, as a mixture of cis and trans diastereomers (from 1.3 : 1 to 440 : 1 cis : trans ratio) and high enantioselectivities (up to 99% ee) (Scheme 16).

Pioneer work from Toste 49 has also shown that, alkynylcyclopropanols could be employed in gold-mediated ring expansion, thus delivering alkylidenecyclobutanones. More recently, an enyne system has been tethered by a cyclopropane ring 52 and the gold-catalysed ring expansion provided, in this case, a tetrasubstituted methylenecyclobutanone 53 (Scheme 17). 50 The proposed mechanism has been supported by a range of experiments, as well as DFT calculations. The reaction proceeds through a ring expansion induced by a gold-complexation to the alkyne 54. Intermediate 55 then isomerises to carbenoid 56.

The ensuing [3,3]-sigmatropic rearrangement affords the cyclobutanone 57, which then undergoes a [1,2]-alkyl shift in presence of a catalytic amount of water.

Finally, an intermolecular gold-mediated reaction between 1,6enynes 58 and a cyclopropene derivative 59 has been envisioned by Matsuda et al. (Scheme 18). 51 Mechanistically, the cycloisomerisation to 60 could occur first and the latter could react with the cyclopropenone 59 to generate the corresponding oxocarbenium ion intermediate 61. A stepwise intramolecular [3+2] reaction to cyclopentenone 62 via intermediate 63 could deliver the spirocyclic structure 64 . This last example is related to a semipinacol rearrangement but cannot be classified as such since the ring expansion occurred via a 1,3-alkyl shift. However, it was worth underlining this ring-expansion of small-size ring leading to the synthetically challenging spiro structure.

Photoredox catalysis is another mean to achieve semipinacol rearrangements. Accordingly, Sahoo et al. reported in 2015, the visible-light induced b -trifluoromethylation of cyclopentanones starting from the corresponding alkenylcyclobutanols (see previous section for an ionic example of trifluoromethylation/ semipinacol rearrangement cascade). 52 On the other hand, a N-centred radical 65 generated via visible-light photocatalysis was reported by Liu et al. and reacted on an alkylidene cyclopropane 66 as a precursor to the transient cyclopropanamine cationic species 67 (Scheme 19). 53 The latter could then undergo an aza-semipinacol rearrangement to the cyclobutanimine 68 . This strained derivative was thereafter utilised, for the synthesis of butyrolactone 69 exhibiting a quaternary carbon centre, therefore demonstrating the synthetic power of the described method.

Finally, we wanted to end this section with a transition metal-free domino reaction. In presence of a chiral Lewis acid catalyst, a -silyloxyacroleins 70 and donor-acceptor diazo derivatives 71 underwent a one-pot cyclopropanation/semipinacol rearrangement cascade reaction (Scheme 20). 54 The chiral oxazaborolidinium ion catalyst (cat) delivered the corresponding a ,b -substituted-cyclobutanones 72 (including a b -quaternary centre) in high yields (up to 91%) and with excellent enantio-and diastereoselectivity (up to 98% ee and up to 420 : 1 dr). Derivatisation of cyclobutanones to various cyclic building blocks (g-lactones, cyclobutanols, cyclopentanones) highlighted the synthetic potential of the method.

3.1.2. Semipinacol rearrangement of alkenyl cyclobutanols. The semipinacol rearrangement of alkenyl cyclobutanols has been the focus of great attention until to date and has allowed the concomitant formation of the corresponding cyclopentanones with the challenging installation of an a -quaternary stereocentre. 42,55,[START_REF] Lukamto | For selected examples on the semipinacol rearrangement[END_REF] In the literature, two types of mechanisms of the domino functionalisation/rearrangement of cyclobutanols to cyclopentanones has been identified: either electrophile-induced or radical-initiated rearrangements. 10 The idea is to develop a full or latent cationic charge a to the tertiary alcoholic carbon, to trigger the ring expansion. Recent advances reported the installation of a-fluoromethyl, 57 b-selenyl, 58 b-thiocyano, 59 b-sulfenyl, 60 b-trifluoromethyl 61 and b-sulfonyl 61,62 cyclopentanones (Scheme 21). Compared to previous strategies, these metal-free approaches advantageously occurred under mild conditions, were often environmentally benign and provided good yields of the desired products. For instance, Chen and Zhang described the first electrochemical trifluoromethylation and sulfonylation/semipinacol rearrangements of allylic alcohols using readily available R'SO 2 Na (R 0 = CF 3 , Ph). 61 Despite important breakthroughs in the field of catalytic asymmetric pinacol rearrangements, 63 within these recent examples, [57][58][59][60][61] sole two of them were developed in their enantiomeric versions and were worth underlining here. In the Lewis acid-mediated thiocyano rearrangement of alkenyl cyclobutanols 73, 59 preliminary studies have shown that chiral BINAM-derived selenide (S)-74 catalyst, 64 in presence of MsOH at À10 1C, could furnish 65% of expected adduct 75 with an encouraging 19% enantiomeric excess, via intermediate 76 (Scheme 22).

On the other hand, enantiomeric excess up to 98% have been noted in the Lewis base/Brønsted acid co-catalysed sulfenylation/semipinacol rearrangement of di-77 and even trisubstituted 78 allylic alcohols (Scheme 23). 60 This stereoselective installation of a sulfur substituent proved later on useful in the total synthesis of (À)-herbertene (79). Moreover, such a strategy allowed the installation of two contiguous stereocentres (one being a quaternary one). Obviously, organosulfur derivatives represent attractive features. They are not only required in the field of bioactive natural products and medicines, but also in the design of chiral catalysts/ligands as well as material science.

Still in the framework of developing stereoselective metal-free ring expansions of alkenyl cyclobutanols, Zhang and Tu 65 The same authors reported an elegant total synthesis of lycojaponicumin A ( 85), a fawcettimine-type alkaloid using, once again, the semipinacol ring expansion as a key step to reach the AB core of the natural product (Scheme 25). The challenged spiro derivative 86 was formed in 84% yield (over 2 steps), starting from the corresponding cyclobutanol 87 and, by simple treatment with a Lewis acid. 66 In the following paragraph, we wish to point out that recent progresses have mostly been devoted to semipinacol rearrangements of cyclobutanols as integral part of domino reactions for the synthesis of complex polycyclic skeletons. [START_REF] Ma | cycloaddition/aza semipinacol ring expansion[END_REF] Simple ring systems were readily available starting points to create synthetically daunting structural motifs such as intricated polycyclic structures and congested quaternary carbon centres. For example, a catalytic asymmetric one-pot [3+2] cyclisation/semipinacol rearrangement sequence gave birth to multi-substituted 3H-spiro[benzofuran-2,2 0 -cyclopentane] skeletons 88 (21 examples, up to 67% yields, up to 92% ee and up to 420 : 1 dr) (Scheme 26). 68 Another sequential cascade reaction featured a semipinacol rearrangement/Michael addition/Henry reaction and allowed the formation of (6,5,5)-fused tricyclic backbones 89, presenting five contiguous stereocentres, including a quaternary carbon centre and a tetrasubstituted one (Scheme 27). 69 This step-, atom-economic transformation was mediated by simple Lewis acids, namely TMSOTf and TiCl 4 , and provides high diastereoselectivities with a broad substrate scope.

To conclude, alkenyl cyclobutanols are excellent partners to produce cyclopentanones via [1,2]-alkyl shift triggered by a vicinal unsaturation. The recent progress put emphasis on metal-free and, preferably, stereoselective reactions. Additionally, to explore the synthetic viability of the method, the installation of an a-quaternary stereocentre was utilised as part of domino reactions in the total synthesis of natural products.

In a similar fashion, the Tiffeneau-Demjanov reaction and the Wagner-Meerwein [1,2]-alkyl shift represent just alternative to the more common semipinacol rearrangement. The Tiffeneau-Demjanov reaction in presence of a diazo derivative, allows the ring extension of cyclopropanones and cyclobutanones to the corresponding cyclobutanones and cyclopentanones respectively, in high yields and selectivities. The less substituted carbon usually migrates with retention of configuration. 70 Excellent achievements have been reported for the asymmetric version of the reaction and the described systems delivered high levels of enantioselective induction. 71 Despite these interesting features only few examples were found in the recent literature. 72 It seems like these kinds of transformations had their finest hours in the late nineties and early years of this century. For those reasons, this topic shall not be addressed in this report. Nowadays Tiffeneau-Demjanov ring enlargement could have its rebirth if involved in novel cascade processes and/or as a key step in the synthesis of natural products.

Wagner-Meerwein rearrangement

The metal-mediated Wagner-Meerwein process often involves an initial cycloisomerisation via activation of a vicinal unsaturation followed by the [1,2]-alkyl shift into the cyclopropylmethyl cation (or carbene) thus created. This past decade, two different type of starting materials and an intermediate have been reported to engage in this ring expansion: on one hand, the methylenecyclopropanes (MCPs) and the alkynyl cyclopropanes and, on the other hand, the carbenoid intermediates. Accordingly, this rearrangement is mostly dominated by the metal-mediated ring opening of MCPs and, has been reviewed twice lately. 73 Consequently, sole the MCP rearrangements since 2019, will be highlighted here. We advise the reader to these two publications for documentation and discussion.

3.2.1. MCP rearrangements since 2019. Methylenecyclopropanes are useful building blocks for the construction of elaborate structures containing four-membered rings. Being highly strained (38.8 kcal mol À1 ), they are prone to oxidative addition. Zhao et al. reported the enantioselective construction of strained spiro[2,3]hexanes via a cascade reaction (Scheme 28). 74 Formation of the iminium ion from the corresponding enal in presence of a secondary electron deficient amine is followed by a Michael addition onto the electronrich MCP 90. Then, a concerted process for the formation of the new cyclopropane unit and, the ring expansion of the cyclopropyl 91 onto the electrophilic adjacent carbon centre, provides the bicyclic spiro system 92 after hydrolysis of the iminium. Moderate to excellent yields were obtained with high diastereoand enantioselectivities. This approach represents a highly versatile method giving access to more complex structures that would be difficult if not impossible to synthesise with single cyclisation reactions. This is also an opportunity to explore and expand the chemical space to enable drug discovery.

Yu employed the rearrangement of MCPs synthetic tool, for a stereoselective access to azepine-fused cyclobutanes (Scheme 29). 75 When yne-MCP 93 was submitted to a chiral gold catalyst L 2 (AuSbF 6 ) 2 , a cyclopropanation/C-C bond cleavage/Wagner-Meerwein rearrangement sequence took place. The corresponding 3-azabicyclo[5.2.0]nonadienes 94 were obtained with excellent enantioselectivities. According to DFT calculations, the chirality of the final product would come from the cyclopropanation step via a chirality-memorised Wagner-Meerwein rearrangement. Many natural products with significant biological activities have cyclobutane moieties. 4b,45a,76 Therefore, efforts to develop methods to synthesise these motifs are highly required so that synthetic chemists could have more tools in their efficient target-, diversity, and function-oriented synthesis. Carreira, demonstrated recently that the yne-MCP rearrangement could be utilised as a key step in the total synthesis of the harziane diterpenoid (95). 77 The tricyclic fused structure 96 was gratifyingly obtained in 87% yield, with a 411 : 1 dr, thanks to a Au-mediated cycloisomerisation (Scheme 30). Finally, and in a very impressive way, Carreira and Gershoni-Poranne elegantly demonstrated that the MCPs could be involved in a Lewis acid mediated cycloisomerisation (Scheme 31). 78 No late transition metal was required and the polycyclic backbone of natural products 97, like repraesentin F, 79 illudiolone 80 or sterpurene, 81 could be reached easily and diastereoselectively, via a Prins addition/ring expansion/1,2-silyl shift domino sequence. The presence of the silicon group proved not only useful for the b -stabilisation of the transient cationic derivative 98, but also served as an entry point for further functionalisation.

To conclude, the Wagner-Meerwein rearrangement of MCPs provides a stereocontrolled access to fused and spirocyclic polycyclic structures, in readiness for further applications.

3.2.2. Ring expansion of alkynyl cyclopropanes. A Rh(II)mediated chemoselective oxidative amination cascade of 1-(alkynyl)cyclopropyl methylsulfamates 99 have been reported by the group of Shi 82 and allowed the construction of the corresponding four-membered rings fused to a heterocyclic system 100 (Scheme 32). Scope and limits of the reaction have been studied and the observed yields were between good to excellent. The electronic nature of the substituent on the alkynyl part did not seem to have any significant effect. Accordingly, the reaction tolerated both electron withdrawing and electron donating groups on the alkynyl part. Further calculation using Density-Functional Theory (DFT) by the same authors, gave insights into the reaction mechanism and they concluded, that the undertaken path involved a metallonitreneinitiated alkyne oxidation cascade. 83 Both gold 84 and ruthenium 85 catalysts have also been utilised in the ring expansion of alkynylcyclopropanes 101 in presence of sulfonamides 102 to afford the corresponding alkylidene-cyclobutanamides 103 (Scheme 33). After the ring expansion to the cyclobutane ring 104, the cationic species could be intermolecularly trapped by the sulfonamide 102. Interestingly, Yi et al. 84 employed a heterogenous gold catalyst, therefore allowing its easy recycling and a procedure more environmentally friendly (Scheme 34).

3.2.3. [1,2]-Alkyl shift onto an intermediate carbenoid. Gold catalysis has also proven efficient in [1,2]-alkyl shift onto an intermediate carbenoid, kind of approach. For instance, Fensterbank described the cycloisomerisation of O-tethered 1,6-enynes 105 exhibiting, within the link, a four membered ring. 86 The authors involved a ring expansion onto the transition-metal-stabilised carbocation intermediate 106. The corresponding fused tricyclic system containing a dihydropyran moiety 107 was obtained in good yields (except for unstable compound 107a R 1 = Ph, R 2 = H, which decomposed only in few hours as a solution in deuterated chloroform). It was next demonstrated that a two-step sequence could deliver valuable macrocyclic ethers like 108, key structural units present in several natural products. [START_REF] Driggers | For selected examples of natural products[END_REF] Echavarren also extensively studied the gold-mediated Wagner-Meerwein rearrangement but in an intermolecular fashion. 88 Satisfyingly, poly-substituted cyclobutenes 109 were obtained from very simple substrates, via the ring expansion of a gold carbene 110 (Scheme 35). It was thus demonstrated, that the formal [2+2] intermolecular cycloaddition reaction between electron-rich alkyne 111 and alkenes 112, occurred in very good yields. 1,3-Butadienes 113 have also been isolated in the case of ortho-substituted arylalkynes or electrondeficient alkynes. Mechanistically, a metathesis type path has been proposed. The course of this reaction has been the subject of extensive studies. 88b Starting from 1,3-enynes, 1-vinyl-3substituted cyclobutenes 89 could be obtained (see for instance 114). The latter served as key starting materials to more complex structures like cyclopentenes, 2,3-dihydrofurans or even the protoilludane core.

A cyclobutanol exhibiting an a-diazo derivative 115 was described in a paper published in 2013 by Chen et al. 90 The diazo function was advantageously transformed into a rhodium-carbenoid intermediate, which could spontaneously undergo a rearrangement to the zwitterionic species 116 (Scheme 36). Thereafter, the urea-based squaramide catalyst could enable the enantioselective Michael addition of intermediate 117 onto a nitroolefin 118. This metal/chiral bifunctional organo combined catalysis allowed the formation of the corresponding cyclopentanone 119 in excellent yields (up to 99%), with high diastereo-and enantioselectivities and, moreover, the creation of a quaternary stereocentre. The strategy employing a diazo function a to the cyclopropyl derivative, a well-known precursor of carbenoids, and as a mean to trigger the Wagner Meerwein rearrangement, had precedent in the literature. 91 It was even utilised as a key step in the total synthesis of pipercyclobutanamide A and piperchabamide G. 92 However, Gong's work is the first report of an enantioselective version. Additionally, the authors demonstrated the compatibility of the transition metal-based catalyst with a chiral bifunctional urea one.

To go even farther in this kind of approach, Tang reported a one-pot copper-and silver-catalysis allowing the ring expansion of alkynyl cyclopropanes 120 to highly substituted cyclobutenes 121 (Scheme 37). 93 First, the copper catalyst could mediate the cycloaddition to the N-sulfonyl 1,2,3-triazole 122. This stable equivalent of diazo derivative could decompose to the corresponding carbenoid in presence of silver triflate. Finally, the Wagner-Meerwein rearrangement could be followed by an elimination step and an alumina oxide treatment would deliver the observed cyclobutenes 121.

An example reported last year by Aggarwal and co-workers, stood out from the crowd and could not be included in the above sub-sections. 94 A Wagner-Meerwein ring expansion, triggered by the electrophilic activation of vinylcyclopropyl boronate complexes 123 with an iminium salt, was elegantly accompanied by a 1,2-R-migration (Scheme 38). It was demonstrated that the reaction was compatible with both Grignard and organolithium reagents. The scope was broad and the 1,2substituted cyclobutyl boronic esters 124 were isolated in good yields, with high diastereoselectivites. From a structural point of view, spirocyclic scaffolds could be formed and cyclobutanes with up to three contiguous stereocentres were observed. Interestingly, the authors applied this approach to a short stereoselective synthesis of (AE)-grandisol (125).

To summarise, the 1,2-alkyl migration for the ring enlargement of polyfunctionalised scaffolds is often part of a domino reaction. Such transformations have been elegantly applied to the synthesis of synthetically challenging structures and can involve the formation, cleavage or migration of up to three C-C or C-X bonds. Efforts have also been carried on developing enantioselective processes. The vast majority of applications showcase the rapid build-up of complex structural motif such as quaternary carbon centres. It is also worth underlining that the field of 1,2-alkyl migration is largely dominated by gold catalysis. On one hand, the p-character of the C-C bonds in a cyclopropane unit provides the kinetic opportunity to initiate the ring-opening, as do C-C multiple bonds through binding 95 and, on the other hand, is responsible for its hyperconjugation. A stabilised non-classical carbocation is thus created.

Group 3: pericyclic reactions

The last part is devoted to the ring expansion of three-and fourmembered rings according to a pericyclic reaction pathway. A general scheme (Scheme 39) provides an overview of the different approaches at a glance. In other words, the ring expanded product generally results from either sigmatropic rearrangements ([1,3]-carbon shift, [3,3]-Cope rearrangement) or electrocyclic processes. In fine, the purpose of this section is to highlight the added value of using pericyclic reactions, to access challenging structural motif such as congested quaternary carbon centres, medium-size rings, spiro moieties.

4.1. Sigmatropic rearrangements 4.1.1. Cope rearrangement. With their 601 bond angles (compared to the classical 1091 for typical Csp 3 -Csp 3 bonds), cyclopropane units are small rings with considerable double bond character. Their reactivity can indeed be compared to that of alkenes. In that context, the divinylcylclopropane-cycloheptadiene rearrangement was first observed in 1960 by Vogel (Scheme 39). 96 The thermal Cope rearrangement involving the ring opening of a strained cyclopropane became quite famous in the eighties. 97 This catalyst-free versatile method for the formation of seven-membered rings possesses outstanding atom economy and, overall high degree of stereocontrol. Accordingly, the requirement of a boat transition state allows the impressive C-C s-bonds formation in a highly stereospecific and predictable manner. 98 Moreover, the transposition is driven by the release of ring strain and therefore occurs at significantly lower temperature than the classical acyclic 1,5dienes. This method has quickly found application in the synthesis of complex unnatural and natural products. However, one major drawback lied in the necessary construction of a cis relationship between the alkene substituents in the starting material, therefore lowering down the attractiveness of such a promising process. In 1998, Davies elegantly overturned this weakness by employing Donor-Acceptor diazo derivatives (Scheme 40). Not only a high diastereoselectivity and enantioselectivity in the Rh-mediated cyclopropanation step were secured, but also, by using a vinyl diazo derivative, the authors were able to perform the [3,3]-sigmatropic rearrangement in the same pot. 99 This formal (4+3) reaction set the stage for many elegant strategies and considerably shortened the path to molecular complexity. 97b,100 More recently, Taylor studied the Cope rearrangement of gem-dimethyl substituted divinylcyclopropanes. 101 The authors showed that the Cope rearrangement of trans-divinylcyclopropanes could take place given that higher reaction temperature, 130 1C in boiling xylenes for 17 hours, were utilized (Scheme 41, eqn (1)). From a mechanistic point of view, a trans-/cis-epimerisation of the divinylcyclopropane via a diradical cyclopropane opening, could first take place and, a subsequent Cope rearrangement could afford the corresponding 1,4-cycloheptadiene. The authors next demonstrated the inhibiting effects of the gemdimethyl substituents on the trans-/cis-isomerisation. The starting materials failed to deliver the product (Scheme 41, eqn (2)) but the corresponding cis-divinylcyclopropanes gave full conversion to the medium-size ring system (Scheme 41, eqn (3)).

Scheme 39 Classical pericyclic reactions of cyclobutanes and cyclopropanes. In light of the impressive amount of work already described on the subject in the past decades, we decided to focus, in this section, on recent applications towards the total synthesis of natural products and/or creation of high molecular complexity via cascade reactions.

Stoltz reported very recently, an enantioselective approach toward the polycyclic core of curcusones ( 126) and used the divinylcyclopropane strategy as a key step to reach the sevenmembered ring (Scheme 42). 102 Ring opening of lactone 127 in presence of DIBAL provided diol 128 together with trace amount of the desired ring expanded cycloadduct 129 . Accordingly, gentle heating (50 1C) of the crude mixture in benzene pleasingly converted to completion the remaining cisdivinylcyclopropane, thanks to a Cope rearrangement. The tricyclic system was obtained in 31% overall yield. A boat transition state set the relative stereochemistry at the junction of the seven-and five-and six-membered rings respectively. The expected compound was delivered as a unique diastereomer. Interestingly, this rearrangement required a prior strain release to be effective. In other words, the presence of the lactone tethering the system, allowed to temporarily mask the divinylcyclopropane function.

The same group has also been interested, for few years now, in the furanobutenolide-derived polycyclic norcembranoid diterpenes. 103 All approaches rely on a diastereoselective Cope rearrangement. More precisely, they developed a straightforward access to the [6,7,5,5] tetracyclic core of ineleganolide (130 ). 104 Three complementary domino sequences were reported by the authors. To get straight to the point, the divinylcyclopropane 131 could not undergo, as anticipated, a direct Cope rearrangement since it would lead to a highly strained embedded cycloheptadiene 132, presenting two anti Bredt bridgehead alkene (Scheme 43). However, if 131 was treated with lithium hydroxide in cold and wet THF, first an acetate cleavage could take place, followed by a translactonisation disrupting the bridged system. Finally, the [3,3]-sigmatropic rearrangement of the less strained three-membered ring 133 could provide the desired intricated tetracyclic structure 134 in 55% yield. During this domino sequence featuring a small-ring expansion, two single bonds and a tertiary stereogenic centre were created with total diastereoselectivity. Importantly, a transcycloheptadiene was reached, representing the first reported synthesis of the (6,7,5,5) tetracyclic core of ineleganolide (130 ). This transformation was ''effortless'' since such a framework simply and spontaneously rearranged.

In 2012, a concise route to the core of molecules isolated from the Schisandra genus was reported [see for instance lancifodilactone F ( 135 The gold-or platinium-catalysed cycloisomerisation of dienyne as part of a cascade sequence with the subsequent divinylcylclopropane-cycloheptadiene rearrangement, has been described on several occasions and all papers related to the subject, elegantly set polycyclic structures exhibiting a cycloheptadiene. 106 The target was reached in 13 steps on the longest linear sequence and, remarkably, it is a completely protectinggroup-free approach. The authors chose to run a stepwise strategy on (E,E)-dienyne 144 to reach higher diastereoselectivity (3.2 : 1 dr). However, it should be underlined that a onepot reaction cascade was also feasible and led as well to the desired polycyclic structure 143 (83%, 1.9 : 1 dr).

Another approach starting also from dienyne, was reported by Chen. 108 The authors set an elegant formal gold mediated (4+2+1) cycloaddition reaction to access [5.3.0] substituted bicyclic compounds. The intermolecular reaction between dienyne 145 and a donor-acceptor diazo compound 146 in presence of a NHC-Au(I) catalyst, provided adduct 147 in very good yields (Scheme 46). More importantly, this cascade reaction allowed the challenging diastereoselective formation of a quaternary centre. Nevertheless, the scope of the reaction is limited to aryl groups on the diazo derivative. However, compounds bearing electron-withdrawing or electrondonating groups on the phenyl substituent showed similar reactivity, indicating that the electronic nature does not play an essential role in the transformation. Hypothetically, the nucleophilic addition of the diazo derivative 146 on the gold intermediate 148 should lead to intermediate 149 via TS-150. According to the authors, the latter is the most favoured one because of reduced steric interaction and possible Au-O interaction. We believe the presence of a donor component (aryl group) on the diazo derivative to be essential to increase the nucleophilicity of the diazo compound, thus, explaining why the simplest ethyldiazoacetate did not react. Finally, an elimination step followed by the Cope rearrangement could deliver the bicyclic structure 147. The reaction is quite sensitive to steric encumbrance, since substitution on the diene required harsher reaction conditions (24 hours in boiling toluene), for the [3,3]-sigmatropic rearrangement to occur. Otherwise, the divinylcyclopropane 151 is instead isolated.

The reaction of diazocarbonyl derivatives with arenes (otherwise known as Buchner ring expansion) can be thought of as a special case of divinylcyclopropane rearrangement. This onepot, two-step reaction has been thoroughly described 109 and was recently reviewed. 110 It has been part of elegant reported total syntheses. 111 A current example was devoted to the asymmetric synthesis of (5,7)-fused ring systems. 112 The authors focused their efforts on finding conditions: (i) preventing the formation of the so-called b-elimination side products and (ii) providing the highest possible enantiomeric excesses. The intramolecular rhodium-mediated cyclopropanation of the arene part 152 followed by a ring-opening to the cycloheptatriene 153 set the challenging stereochemistry of the quaternary carbon centre at the ring junction in good yields and competitive enantioselectivity (Scheme 47).

Preparation of cyclooctadiene-containing systems through Cope rearrangement from divinylcyclobutanes this time, is also a well-known process 113 and is often obtained via a [2+2] cycloaddition of 1, 3-dienes. 114 This kind of approach has proven useful in the total synthesis of natural products. 115 Herein, we wish to highlight the elegant and original work reported from the group of Daugulis. 116 En route to helicene, they developed a strategy starting from phenols. When the latter was submitted to four equivalents of chlorobenzene in presence of LiTMP in a THF/pentane mixture at room temperature, the corresponding helicene 154 was obtained in 67% yield (Scheme 48). The mechanism suggested by the authors could involve a [2+2] reaction between benzyne and phenolate affording the four-membered ring 155. Next a Cope rearrangement of the divinylcyclobutane 155 could furnish the eight-membered ring 156 which, after reacting with a second equivalent of benzyne could deliver the tetracyclic structure 157. Ring opening of the latter could deliver the 10-membered ring ketone 158. Finally, a ring contraction/dehydration sequence could afford the observed helicene 154. A similar electrocyclic ring opening leading to benzocyclooctatrienones has also been reported by Yamamoto, and featured a one-pot ruthenium-catalysed cyclisation-iodine-mediated oxidative ring expansion. 117 4.1.2. Other sigmatropic rearrangements. In line, with the Cope rearrangement that we just mentioned, we wanted to first turn our attention to another [3,3] Sigmatropic rearrangement, namely the retro-Claisen type rearrangement. Miura and Murakami proposed a sequence to trans-cycloalkenes via an enantioselective cyclopropanation and a ring expansion. 118 This impressive transformation set the stage for the asymmetric formation of 8-and 10-membered trans-cycloalkenes fused with dehydropiperidine (Scheme 49). This one-pot, two step procedure, featured first an enantioselective cyclopropanation onto the MCP derivative 159, thanks to a chiral rhodium catalyst. The resulting The interesting biological activity profile and structural complexity of cyclopenta [b]naphthalene moieties have drawn significant attention 119 and Shi proposed a straightforward access to this kind of structural motifs starting from the famously strained and reactive methylenecyclopropenes. 120 Under acidic conditions and in presence of a nucleophile (like indole or pyrrole) in the reaction mixture, the propargyl alcohol 163 underwent a cascade reaction to the polyaromatic structure 164 (Scheme 50). First, the carbocationic intermediates 165 could react with pyrrole (or indole) at the 2-or 1-position leading to intermediate 166 or side product 167. Upon heating a 6p electrocyclisation followed by a formal [1,3] sigmatropic alkyl shift driven by a rearomatisation could provide the desired cyclopenta [b]naphthalene skeletons 164 in very good yields.

The recent strategic applications of the sigmatropic rearrangements have been described. They all showcase the significant role of this type of ring expansion in the design of efficient and stereocontrolled synthetic routes. The most appealing approaches started from acyclic starting materials. The corresponding smallsize ring were obtained as intermediates and ''spontaneously'' rearranged into more elaborated polycyclic scaffolds. Overall this process is less time-consuming and combined pot, atom and step economy (PASE). 121 It is definitely a source of inspiration for further utilisation, notably in natural product synthesis, or the design and development of novel materials.

Other pericyclic reactions

Assembling complex molecular scaffolds as quickly and as efficiently as possible, is the holy grail of each synthetic organic chemist. Pericyclic reactions and electrocyclic reactions more precisely, is a mean to meet these criteria.

Substituted benzoic acids are quite appealing starting materials for the synthesis of many complicated naturally occurring compounds. 122 In 2015, Magauer developed an interesting strategy to access the 3-hydroxybenzoate subunit. 123 Previously reported methods suffered from poor selectivity and/or low reactivity. 124 For those reasons, the authors came up with an unprecedented approach relying on a thermal 2p electrocyclic disrotatory ring opening of bicyclo[3.1.0]hexane-2-ones followed by an aromatisation step. The bicyclic starting material 168 is easily available from the cyclopropanation of the corresponding cyclopentenone in presence of cheap reagents, namely the lithium enolate of methyl dichloroacetate. The authors quickly demonstrated that the (cis,cis) isomer of 168 was reluctant to undergo the thermally allowed cyclopropyl allyl cation type 2p disrotatory ring opening. Whereas, the (cis,trans)-168 cyclopropane, when heated up to 190 1C in the polar solvent sulfolane, quickly delivered the corresponding 3-hydroxybenzo-ate 169 in excellent yields and regioselectivity (Scheme 51). This transformation turned out to be compatible with a wide range of substituents and could be extended to the synthesis of anilines 170 or phenols 171, when amines or alcohols were respectively used as condensation reagents of the carbonyle group. Later on, the authors showcased their methodology in the total synthesis of the natural product salimabromide (172) 125 and the polycyclic core of chartarin (173). 126 Polysusbstituted phenols are ideally poised for diverse synthetic elaborations by manipulation of their functional groups (for instance, oxidation to the ubiquitous quinones) or by oxidative phenolic couplings. Recently, Hu and coworkers applied a step-economic approach to hydroquinones, reported Scheme 50 Approach to cyclopenta [b]naphthalenes (2020).

by Moore 127 and Liebeskind in the late eighties. 128 The authors used this 4p-electrocyclic ring-opening/6p electrocyclisation cascade for the total synthesis of three naturally occurring products: (AE)-diperezone (174), parvistemin A (175) 129 and (AE)-cereoanhydride (176). 130 The thermally favoured 4pelectrocyclic conrotatory ring opening of cyclobutenone 177 could lead to intermediate 178 which, upon 6p ring-closure and tautomerisation could deliver the corresponding hydroquinones 179 (Scheme 52). A subsequent DDQ oxidation thereafter furnished quinones 180 in 40% yield thus demonstrating the synthetic potential of substituted cyclobutenediones. 131 The natural product (AE)-cereoanhydride (176) was obtained in nine steps only, therefore demonstrating how electrocyclic cascade reactions could shorten the path to complicated molecular structure.

In 2015, Arichi et al. focused their attention on a ring expansion cascade for the synthesis of medium-size ring system starting from a fused cyclobutene (Scheme 53). 132 When cyclobutenes 181 were treated with an iodoaniline derivative in presence of a palladium catalyst in toluene at 100 1C, the cyclooctene-and even the cyclononene-fused indolines 182 were isolated in yields ranging from 45 to 80%. The thermal stereospecific conrotatory 4p electrocyclic ring opening of the cis-fused cyclobutenes would lead to the corresponding cis,trans-cycloalkadienes 183. Then, a Pd(II) complex generated from the oxidative addition of a Pd(0) into the carbonhalogen bond of the iodoaniline reactant, would be involved in a Heck arylation. Interestingly, the authors demonstrated a point-to planar-to point chirality transfer via the transient planar chiral intermediate 183. Another torquoselective 4pelectrocyclic conrotatory ring opening was utilised this time on cyclobutenamides as part of a cascade reaction, and interestingly involved a strained cis,trans-cycloheptadienone intermediate. 133 The AlCl 3 -Lewis acid mediated the ring expansion of 4,5-fused cyclobutenamides 184 to the strained medium-size ring 185 (Scheme 54). Thereafter a Nazarov-like cyclisation followed by a 1,2-alkyl shift provided the [2.2.1] bicyclic ketones 186 in excellent yields. This reaction could also be applied to the 4,6-fused cyclobutenamides (184, n = 2) and therefore furnished the corresponding eight-membered ring adduct. Finally, the authors demonstrated the synthetic potential of their strategy thanks to the synthesis of polycyclic frameworks in one step only and starting from readily available cyclobutenamides (see the preparation of 187, for instance).

The cyclic nature of the transition state of pericylic reactions, associated with the inherent ring strain of cyclopropanes or cyclobutanes, is a clear asset in terms of stereo-and regiocontrol. It is also an efficient trick to reach quaternary centres, which are common structural motifs in many bioactive natural products and pharmaceuticals. The construction of all-carbon quaternary centres has indeed received special attention from the synthetic community. 134

Conclusions

This review intended to highlight the tremendous power and versatility of small ring systems. Cyclobutanes and cyclopropanes derivatives have drawn increasing attention because they constitute valuable building blocks. Their rearrangement reactions represent one of the most attractive applications as they allow enantioselective and diastereoselective formations of chemical bonds, especially in the creation of sterically congested quaternary or tetrasubstituted carbon centre. The presence of multiple functionalities in the products allows further transformations, therefore giving access to more complex structures. For the above-mentioned reasons, recent applications have been found in the total synthesis of natural products. In addition, the ring expansion as a part of a domino cascade reaction seems to be the general trend observed lately, and allow an elegant access to intricate molecular architectures.

To conclude, this small ring expansion strategies clearly have a bright future in synthetic chemistry, since they give birth to libraries of more complex structures that would be impossible or difficult to attain by more classical approaches.

Scheme 2

 2 Scheme 2 Approach to piperarborenine B (1) (2016).

Scheme 3

 3 Scheme 3 Approach to (AE)-steviol (8) (2013).

Scheme 4

 4 Scheme 4 Approach to (AE)-vibralactone (9) (2019).

Scheme 7 [

 7 Scheme 7 [4+2]/ring expansion domino cascade (2019).

Scheme 9

 9 Scheme 9 Approach to a [4.4.1] bicyclic system (2019).

Scheme 13

 13 Scheme 13 Stereospecific construction of metacyclophanes (2014).

Scheme 16

 16 Scheme 16 Stereoselective rearrangement of cyclopropylenynes (2017).

  Scheme 19 Visible-light-induced aza-pinacol rearrangement (2017).

  rearrangement initiated by an enamine radical cation (Scheme 24). The organo-SOMO catalysed sequence between an allylic cyclobutanol 80 and an aldehyde 81 led to the formation of the C-C bond between the two partners with concomitant creation of the first stereocentre. Under oxidative conditions, the cyclobutanol 82 underwent a 1,2-alkyl migration onto the adjacent electrophilic carbon therefore delivering the a -quaternary-dcarbonyl cycloketones 83 in good yields, excellent diastereoselectivities and very high enantioselectivities. An intramolecular version of this strategy successfully furnished the (+)-cerapicol(84) natural product.

Scheme 22

 22 Scheme 22 Catalytic asymmetric thiocyano semipinacol rearrangement (2019).

Scheme 26

 26 Scheme 26 One-pot [3+2] cyclisation/semipinacol rearrangement (2019).

Scheme 29

 29 Scheme 29 Stereoselective access to azepine-fused cyclobutanes (2019).

Scheme 32 A

 32 Scheme 32 A Rh(II)-mediated chemoselective oxidative amination cascade (2017).

Scheme 36

 36 Scheme 36 Approach to a-quaternary substituted cyclopentanones (2013).

Scheme 40

 40 Scheme 40 Davies formal (4+3) cycloaddition reaction.

  ) & micrandilactone B (136 )]. 105 A domino cascade reaction featuring a Pd-mediated Sonogashira coupling/lactonization/Cope rearrangement cascade onto diastereomer 137 allowed the formation of the ABC skeleton 138 of lancifodilactone F (135) in 31% yield, as a single diastereomer (Scheme 44). The sequence during which three single bonds and two stereogenic centres, including a tetracyclic carbon, were created, was thus validated. The diastereoselectivity of the reaction came from: the controlled formation of the Z-exocyclic double bond during the 5-exo-dig lactonisation (see 139 ), followed by a boat transition state for the Cope rearrangement (see 140 ). A further one-pot deprotection-Michael addition gratifyingly delivered the desired tetracyclic backbone 141 of micrandilactone B (136 ) in 64% yield.

  Scheme 42 Approach to the polycyclic core of curcusones (126) (2019).

  Scheme 44 A concise route to the core of molecules isolated from the Schisandra genus (2012).

Scheme 47 A

 47 Scheme 47 A Buchner ring expansion example (2019).

Scheme 49 A

 49 Scheme 49 A retro-Claisen type rearrangement to 10-trans-cycloalkene (2014).

  spiro[2.2]pentane 160 could then undergo a concerted skeletal rearrangement to 161. The resulting trans-alkene would originate from a closed chair-like transition state 162. The reported yields were excellent and high enantiomeric excesses were observed.

  Scheme 51 A 2p-electrocyclic disrotatory ring opening (2015).

Scheme 53

 53 Scheme 53 Thermal stereospecific conrotatory 4p-electrocyclic ring opening (2015).

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Scheme 14 1,2-Atom migration and ring expansion reactions. Scheme 15 Approach to russujaponol D (46) (2013).

Chem. Soc. Rev., 2021, 50, 7513-7538 | 7531

Scheme 54 A 4p-electrocyclic conrotatory ring opening to medium-size bridged systems (2015).

Acknowledgements

Financial support from Aix Marseille University, Centrale Marseille, the CNRS and, the Agence Nationale pour la Recherche (ANR 18-CE07-0005) are gratefully acknowledged.

Notes and references

Conflicts of interest

There are no conflicts to declare.