Synthèse de composés cyclopentaniques chiraux, di, tri et tétrasubstitués. Application à la synthèse de dérivés Oxa‐13‐prostanoïques

Abstract

SummaryThe cyclopentenecarbaldehyde la, acetals 2 a, 2 b and the cyclopentenone 2 c have been transformed through regio and stereocontrolled reactions into a variety of enantiomerically pure substituted cyclopentanes. Using appropriately selected Wittig reagents, aldehyde l a furnished the condensation products 3, 4, 5. Michael addition of diethyl malonate on the a,p-unsaturated aldehyde l a under phasetransfer conditions led efficiently to 7. Reduction of the cyclopentenone 2 c gave 21 in high yield. The cyclopentenes 2a, 2b and 23, submitted to hydroborationoxidation furnished the cyclopentanols 10,13 and 24, respectively, in 30, 70 and 50% yields, reflecting the substitution pattern of the starting alkenes. The salient feature of these reactions is the stereospecificity due to the chiral centre of the molecules la, 2 a , 2b and 2c, leading to compounds with two, three and four asymmetric centres. The straightforward synthesis of 1 la-hydroxy-13-oxaprostanoic acid 20 is described and an approach towards the preparation of 9 a , 1 la-dihydroxy-13-oxaprostanoic acid 34 is also presented. The structure of these products has been determined by 'H-and 13C-NMR spectroscopy.Introduction. -Un effort considkrable a ttC dkploye durant les dix dernieres annees pour la preparation d'analogues de prostaglandines plus stables et a activite plus specifique que les composks naturels [ 11. Cependant, si la plupart des synthhes rkaliskes utilisent des resolutions [2] ou des transformations enzymatiques [3], une des mkthodes de choix pour la synthese de composks knantiomkriquement purs est l'emploi d'un produit de depart nature1 chiral [4]. Nous avons rkcemment decrit [5] la synthese de cyclopentenes chiraux du type I et 11, partir de l'acide D ( -) -quinique et decrivons, dans ce memoire, quelques-unes de leurs transformations ainsi que leur utilisation pour la synthese d'analogues oxa-13 de l'acide

Synthesis of Acyloxy‐Semicyclic Dienes Using an Enyne Metathesis/Ring Closing Metathesis Approach

“…Some of these methods require proton abstraction in the cyclohexyl ring which can lead to regioisomeric mixtures, whereas the Heck‐type reactions can also result in the formation of regioisomeric mixtures. Furthermore, functionalisation at the allylic position of the resulting semicyclic diene is not trivial; published examples with a substituent allylic to the 1,3‐diene moiety are rare 2d,2e,3a,12…”