Synthesis of 2‐Methyl and Ethyl‐Substituted 19‐nor‐1α,25‐Dihydroxyvitamin D₃ Analogues via the Cyclovitamin Strategy

Abstract

The synthesis of several 19-nor-2-alkyl-1α,25-dihydroxyvitamin D 3 analogues (5-14) is described following the cyclovitamin strategy. Starting from all-cis methyl 3,5-dihydroxy-4-alkyl-1-cyclohexanecarboxylate (29), the eight stereoisomeric A-ring-precursor 2-tert-butyldiphenylsilyloxy-3α-formyl-1-alkylbicyclo[3.1.0]hexanes (39, 44, 46, 63, 65, 67, 69, 71) were prepared in two series: a (R = methyl) and b (R =

Organocatalytic Transannular Approach to Stereodefined Bicyclo[3.1.0]hexanes

“…In general, the enantioselective synthetic routes described to date typically involve the formation of the cyclopropane ring from a conveniently functionalized cyclopentane substrate, either through a ring-closure event or through a [2+1] cycloaddition process (see Scheme ). , However, the possibility of constructing the bicyclo[3.1.0]­hexane scaffold in a stereoselective manner by transannular C–C bond formation starting from a conveniently functionalized cyclohexane derivative has received very little attention to date, despite the fact that some very early reports indicated functionalized 4-chlorocyclohexanones, 3-bromocyclohexyl esters, or 3-sulfonylcyclohexyl esters are used as substrates undergoing ring contraction via transannular alkylation through enolate formation.…”