REVIEW ▌1 Recentreview Progress in the Synthetic Assembly of 2-Cyclopentenones David2-Cyclopentenone J. Synthesis Aitken,*a Hendrik Eijsberg,a,b Angelo Frongia,b Jean Ollivier,a Pier Paolo Pirasb a Laboratoire de Synthèse Organique & Méthodologie, ICMMO (CNRS UMR 8182), Université Paris Sud, 15 rue Georges Clemenceau, 91045 Orsay cedex, France Fax +33(1)69156278; E-mail: [email protected] b Dipartimento di Scienze Chimiche e Geologiche, Università degli studi di Cagliari, Complesso Universitario di Monserrato, S.S. 554, Bivio per Sestu, 09042 Monserrato, Cagliari, Italy Received: 09.07.2013; Accepted after revision: 21.08.2013 considerable number of ways in which the target ring sys- Abstract: An overview of the most important synthetic strategies currently available for the preparation of cyclopent-2-enones is pre- tem can be created from acyclic precursors, in either inter- sented and illustrated with recent applications. molecular or intramolecular mode. Most of the possible disconnection strategies have been examined, and it is im- 1 Introduction portant to recognize that for any given target 2-cyclopen- 2 Multicomponent Ring Assembly tenone, there may be several convenient approaches 3 Cyclizations available. The main approaches for ring construction are 4 Transformations of Existing Cyclic Systems summarized graphically in Figure 1. 5 Miscellaneous Methods O (4+1) O O (3+2) (3+2) coupling 6 Conclusions 1 1 1 5 5 2 5 2 2 RCM Key words: cyclopentenones, cyclization, carbocycles, ring clo- (4+1) (3+2) Rautenstrauch 4 3 4 3 4 3 aldol-type annulation sure, rearrangement, annulation (2+2+1) PKR Nazarov (3+2) Figure 1 The main ring-construction strategies for 2-cyclopente- none synthesis, showing the atom connectivities made during ring as- 1 Introduction sembly (left and center) and cyclization approaches (right). These and other strategies are covered in this review. Scope of this Review 2-Cyclopentenones are a frequently encountered class of Useful procedures based on the transformation of existing cyclic enone. They feature in many areas of organic chem- cyclic structures also exist, as do some miscellaneous istry and serve as benchmark substrates for numerous methods; these will be treated towards the end of this re- chemical transformations, and natural product structures view. containing a 2-cyclopentenone molecular feature are The ‘ideal’ choice of synthetic route depends both on the ubiquitous. specific features in the target skeleton, such as the pres- Some of the synthetic routes to the title compounds have ence of sensitive functional groups or stereogenic centers, been reviewed periodically1 (see also specific sections), and on contextual constraints, such as the employment (or but a global appraisal has not appeared for some time.2 the preclusion) of metals, heat, particular solvents, and so This review covers the literature over the last decade or on. Control of the relative configuration of 4,5-disubsti- so, and it endeavors to provide an overview of the most tuted 2-cyclopentenones can be achieved either by using a commonly used synthetic approaches for assembling the precursor in which those chiral centers are already estab- eponymous core feature from unrelated precursors. It is lished, or by using an approach in which these centers are structured according to the strategy by which the cyclic created in a diastereoselective fashion, such as the enone feature is created, rather than according to any par- Nazarov or related cyclizations. The preparation of nonra- ticular type of derivative or substitution pattern. New ap- cemic 4- and/or 5-substituted 2-cyclopentenones fre- proaches as well as new results using established ones are quently relies on the use of nonracemic chiral substrates. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. considered equally. The use of chiral auxiliaries during the ring-creation pro- cess has allowed some asymmetric syntheses to be per- The numerous methods available for the generation of 2- formed, but catalytic enantioselective syntheses are rare at cyclopentenones by α,β-elimination reactions of appropri- present; indeed this might constitute an area of particular ately functionalized cyclopentanone precursors fall out- attention for future developments. side of the scope of this review, as do the vast array of oxidations of cyclopentenes, 2-cyclopentenols and cyclo- Applications of the synthetic approaches reviewed herein pentanones. These limitations notwithstanding, there are a have been selected for illustrative purposes as best as pos- sible, but the quantity of work conducted in the area and SYNTHESIS 2014, 46, 0001–0024 the structural diversity of the molecular targets make it Advanced online publication: 21.11.20130039-78811437-210X unfeasible to present an exhaustive list of synthetic appli- DOI: 10.1055/s-0033-1340414; Art ID: SS-2013-E0467-R cations here. © Georg Thieme Verlag Stuttgart · New York 2 D. J. Aitken et al. REVIEW Biographical Sketches█ David J. Aitken was born sur-Yvette) he was appoint- ducted in the ICMMO re- in 1963 and studied chemis- ed CNRS researcher at Des- search institute, include the try at the University of cartes University (Paris). In synthesis of functionalized Strathclyde (Glasgow), ob- 1998 he became Professor small-ring compounds, par- taining his PhD in 1986, un- of Organic Chemistry at the ticularly unnatural amino der the supervision of Prof. University of Clermont- acids, as building blocks for H. C. S. Wood and Prof. C. Ferrand, and in 2006 he foldamers and peptidomi- J. Suckling. After a two- transferred to his current po- metics, and synthetic organ- year post-doctoral appoint- sition as Professor at the ic photochemistry. ment with Prof. H.-P. University Paris Sud (Orsay). Husson at the ICSN (Gif- His research interests, con- Hendrik Eijsberg studied 2008, he joined the group of gliari (Italy) on an organo- at the Ecole Nationale Su- Prof. D. J. Aitken at the Uni- catalysis project. He perieure de Chimie de Paris versity of Paris-Sud (Orsay) finished his PhD in 2012 (France) and carried out un- where he carried out his and joined the group of Pro- dergraduate work on the PhD studies on the photo- fessor I. Marek in the Tech- asymmetric conjugate addi- chemistry of cyclopente- nion Institute (Israel). His tion of organoboron com- nones and alkenes beyond research interests now in- pounds catalyzed by the [2+2] stage. He collabo- clude zirconium-mediated rhodium–diene complexes rated during his PhD with reactions and carbometala- in the group of Prof. J.-P. the group of Prof. P. P. Piras tion of small rings. Genet and Dr. S. Darses. In from the University of Ca- Angelo Frongia was born tive post-doctoral research Chemistry at the Faculty of in Cagliari (Italy) in 1973. in the group of Prof. D. J. Sciences. His research inter- He graduated and received Aitken in the ICMMO, Uni- ests include asymmetric his PhD degree in Organic versity Paris Sud (Orsay), synthesis and development Chemistry from the Univer- he joined the academic staff of new synthetic methods sity of Cagliari under the su- at the University of Cagliari based on transformation of pervision of Prof. P. P. in 2010. He is currently As- strained organic com- Piras. Following collabora- sistant Professor of Organic pounds. Jean Ollivier obtained his ences degree in Organic University Paris-Sud. His PhD degree in 1982 at the Chemistry and then spent a research interests include University Paris-Sud (Or- year (1987) as a postdoctor- the chemistry and applica- say) under the direction of al fellow at the Dyson Per- tions of small-ring com- Dr. J. Salaün, then joined rins Laboratory (Oxford) pounds implicating stereo- the Centre National de la with Dr. S. G. Davies. He and enantioselective reac- Recherche Scientifique then returned to Orsay and tions, ring expansions and, (CNRS). In 1986 he ob- is presently Chargé de Re- more recently, organocatal- tained a Doctorat-ès-Sci- cherche in the ICMMO, ysis. Pier Paolo Piras received 1990–1991 he spent a sab- 2009 he was a Visiting Pro- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. his Laurea in Chemistry at batical year at the Labora- fessor in the University of the University of Cagliari toire des Carbocycles, Paris-Sud (Orsay). His pri- (Italy) in 1971 and began his University of Paris-Sud (Or- mary research interests fo- academic career at the same say) working on cyclopro- cus on the synthesis and university as Assistant Pro- pane derivatives with Dr. J. reactivity of strained carbo- fessor in 1972. He was a Salaün. Returning to Ca- cycles, the synthesis of nat- postdoctoral fellow (1980– gliari, he was appointed As- ural products, and 1981) with Professor C. J. sociate Professor in 1985, asymmetric organocatalytic M. Stirling at the University then full Professor of Or- reactions. of Bangor (North Wales). In ganic Chemistry in 2001. In Synthesis 2014, 46, 1–24 © Georg Thieme Verlag Stuttgart · New York REVIEW 2-Cyclopentenone Synthesis 3 Overview of 2-Cyclopentenone Reactivity cyclopropanations,24 aziridinations,25 and epoxidations26 While the purpose of this review is to relate the main syn- are also feasible reactions. thetic approaches for the preparation of 2-cyclopente- nones, it is useful to present here a brief summary of the chemical reactivity of this molecular core, for two rea- 2 Multicomponent Ring Assembly sons. Firstly, the diversity of chemical transformations that can be carried out thereupon goes some way to ex- 2-Cyclopentenones can be prepared by assembling two or plaining the popularity of the system, and secondly, these more components through the formation of at least two reactivity features should be kept in mind when planning new σ bonds, generally in a sequential fashion. This is a the synthesis of any particular 2-cyclopentenone deriva- versatile and often efficient approach for the construction tive.