Construction of spirolactones with concomitant formation of the fused quaternary centre - application to the synthesis of natural products Alexandra Bartoli, Fabien Rodier, Laurent Commeiras, Jean-Luc Parrain, Gaëlle Chouraqui To cite this version: Alexandra Bartoli, Fabien Rodier, Laurent Commeiras, Jean-Luc Parrain, Gaëlle Chouraqui. Con- struction of spirolactones with concomitant formation of the fused quaternary centre - application to the synthesis of natural products. Natural Product Reports, Royal Society of Chemistry, 2011, 28, pp.763-782. 10.1039/C0NP00053A. hal-00681321 HAL Id: hal-00681321 https://hal.archives-ouvertes.fr/hal-00681321 Submitted on 21 Mar 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. View Online / Journal Homepage / Table of Contents for this issue NPR Dynamic Article LinksC< Cite this: Nat. Prod. Rep., 2011, 28, 763 www.rsc.org/npr REVIEW Construction of spirolactones with concomitant formation of the fused quaternary centre – application to the synthesis of natural products Alexandra Bartoli, Fabien Rodier, Laurent Commeiras, Jean-Luc Parrain and Ga€elle Chouraqui* Received 8th October 2010 DOI: 10.1039/c0np00053a Covering: up to the end of 2010 Polycyclic structures fused at a central carbon are of great interest due to their appealing conformational features and their structural implications in biological systems. Although progress in the development of synthetic methodologies towards such structures has been impressive, the stereoselective construction of such quaternary stereocentres remains a significant challenge in the total synthesis of natural products. This review highlights the progress in the formation of 1- oxaspiro[4.n]alkan-2-ones (2 # n # 7) with concomitant formation of the quaternary spiro centre. 1 Introduction 1 Introduction 2 Oxidation: dearomatisation of phenol to quinone Spirolactones containing natural products represent a large 2.1 Hypervalent iodine(III) 2.2 CAN oxidative coupling class of structurally diverse molecules exhibiting a wide range 3 Reductive cross-coupling of biological activities. Key examples include: drospirenone 4 Radical-based approaches (Fig. 1), a synthetic progestin that is a component of certain Ò 5 Furanyl dienolate-based cyclisation birth control formulations such as Yasmin 28 (marketed by 1 5.1 Alkylation Bayer Schering Pharma), the world’s most popular con- Downloaded by University of Cambridge on 20 March 2012 5.2 Addition onto an imine (vinylogous Mannich) traceptive pill, ranked in the top 200 brand-name drugs by retail 2 Published on 02 February 2011 http://pubs.rsc.org | doi:10.1039/C0NP00053A 5.3 Vinylogous aldol reaction dollars in 2008; and abyssomicin C, a potent antibacterial 6 Cationic rearrangement agent against Gram-positive bacteria, including resistant 7 Use of organometallic derivatives Staphylococcus aureus strains (MIC for a methicillin-resistant 1 7.1 Double acylation strain 4 mgmLÀ ;MiCforavancomycin-resistantstrain ¼ 1 3 ¼ 7.2 Reformatsky-type reaction 13 mgmLÀ ). 7.3 Carbonyl insertion The stereoselective synthesis of spirolactones is a challenging 8 Halolactonisation task, requiring control in the construction of the quaternary 4 9 Pericyclic-type reactions carbon. The presence of the sterically constrained spiro struc- 9.1 Electrocyclisation ture in various natural products of biological importance also 9.2 [2 + 1] photocycloaddition adds to the interest in investigations of spiro compounds. Most 9.3 [2 + 2] cycloaddition of the methods to access spirolactones involve an intramolecular 9.4 Diels–Alder reaction esterification reaction, which is favoured for entropic reasons. 9.5 [3 + 2]-type cyclisation A number of natural products have been obtained by this 5 6 7 10 Miscellaneous approach (e.g. arteannuine, norsecurinine, secu’amanine, 10.1 1,6-Addition 10.2 Dyotropic rearrangement 11 Conclusion 12 Acknowledgements 13 References Aix-Marseille Universite, Institut des Sciences Moleculaires de Marseille, iSm2 – UMR CNRS 6263, Campus Saint Jer ome,^ Service 532, 13397 Marseille Cedex 20, France. E-mail: [email protected]; Fax: +33 4-91289187; Tel: +33 4-91289188 Fig. 1 This journal is ª The Royal Society of Chemistry 2011 Nat. Prod. Rep., 2011, 28, 763–782 | 763 View Online stemonamide8). Since this strategy requires the prior installation transformations allowing the formation of a quaternary stereo- of the tertiary alcohol, these methods will not be covered within centre (still one of the most challenging tasks in organic this review. Instead, we will focus on transformations involving synthesis). the creation of the spirolactone concomitant to cyclisation with Herein, we will cover the synthesis of spirobutenolides and the fused stereocentre – potentially powerful synthetic more specifically the 1-oxaspiro[4.n]alkan-2-ones (2 # n # 7) (Fig. 2). This review will discuss different methods to create simulta- neously the spirolactone and the quaternary spiro stereocentre Alexandra Bartoli was born in and their application to the synthesis of natural products. Marseille (France) in October This will be divided either into categories of reaction or species 1984. She obtained her BSc in used: oxidation, reduction, radicals, dienolate, cationic rear- chemistry in 2006 and her MSc rangement, organometallic derivatives, halolactonisation, peri- in 2008, both from the Uni- cyclic reactions. versite Paul Cezanne in Mar- Spirocyclic structures have already been the subject of 9,10 11 seille, where she is currently a number of reviews, including those devoted to spiroketals 12 pursuing her PhD under the and spirocyclic ethers, and the reader is directed to these articles supervision of Dr Gaelle€ Chour- for discussion of these topics. aqui and Dr Jean-Luc Parrain. Her research focuses on the development of new methods to access polycyclic compounds Jean-Luc Parrain obtained his Alexandra Bartoli and spirolactones. PhD in Chemistry at the Fabien Rodier was born in University of Nantes (France) Nˆımes (France) in June 1984. under the supervision of In 2006, he joined the University Professor Jean-Paul Quintard. of Montpellier (France) where After post-doctoral studies in he was awarded his BSc in the laboratory of Professor chemistry. He then moved to the Steve Davies at the University of Ecole Nationale Superieure de Oxford (UK), he joined the Chimie de Montpellier CNRS as ‘‘charge de recherche’’ (ENSCM), where he obtained at the laboratory of Organic his MSc in chemistry. He is Synthesis of the University of currently pursuing his PhD Nantes. In 1995, he moved to the Downloaded by University of Cambridge on 20 March 2012 under the supervision of Dr Jean-Luc Parrain University of Marseille and then Published on 02 February 2011 http://pubs.rsc.org | doi:10.1039/C0NP00053A Gaelle€ Chouraqui, Dr Laurent was appointed a CNRS ‘‘direc- Fabien Rodier Commeiras and Dr Jean-Luc teur de recherches’’ in 2001. His Parrain at the Universite Paul research interests include new catalytic reactions toward new Cezanne in Marseille (France). synthetic methods, development of new organotin and silicon His research focuses on the synthesis of spirolactone moieties using reagents and total synthesis of natural compounds. [5 + 2] cycloaddition. Gaelle€ Chouraqui obtained her Laurent Commeiras was born in PhD in 2003, from the Uni- Marseille (France) in 1975. versite Pierre et Marie Curie After studying chemistry at the (Paris, France), where she Universite Paul Cezanne in worked under the guidance of Marseille, he received his PhD Professor Max Malacria and Dr degree in 2002 under the super- Corinne Aubert. After a two- vision of Dr Jean-Luc Parrain, year stay as a Postdoctoral working on the total synthesis of Research Fellow with Professor terpenoids isolated from algae of James H. Rigby at Wayne State the order Caulerpales. After University (US), she returned a postdoctoral position in the to Europe and completed laboratory of Professor Sir Jack a further year as a Postdoctoral E. Baldwin at the University of Ga€elle Chouraqui Research Fellow in Professor Laurent Commeiras Oxford (UK), he became Ian Paterson’s laboratory at Lecturer at the University of Cambridge University. She was Marseille. His main research appointed CNRS Tenured-Researcher in 2007 at Aix-Marseille interests include the total synthesis of natural and biologically University (France), and her research interests are centred on new active compounds. methods for the synthesis of natural products. 764 | Nat. Prod. Rep., 2011, 28, 763–782 This journal is ª The Royal Society of Chemistry 2011 View Online This methodology was next extended to a domino reaction featuring the Wessely-type intramolecular oxidation18 followed by an intermolecular Diels–Alder reaction (Scheme 3).19 Unlike previously reported examples, phenol 6 bears the carboxylic acid Fig. 2 suitably tethered at the ortho position. An additional functional group para to the alcohol circumvents any trapping at that 2 Oxidation: dearomatisation of phenol to quinone position. Treatment of phenol 6 with BTIB provided