Formation of cyclized, including 3,5-cyclosteroid, alkenes from β,γ-unsaturated Grignard reagents induced by elimination of a δ-alkoxy group

Abstract

Grignard reagents and lithium salts prepared from the epimers of 3β-chloro-7ξ-methoxycholest-5-ene, (2) and (3), were shown to undergo a stereoselective rearrangement/elimination process to give 3α,5α-cyclocholest-6-ene (6) as the major product. Similarly the Grignard reagent from a mixture of (Z)- and (E)-5-chloro-1-methoxy-2-phenylpent-2-ene, (10) and (11), gave 1-cyclopropyl-1-phenylethene (9). Reactions of the corresponding Grignard reagents lacking methoxy groups with water or carbon dioxide gave unrearranged products. It was concluded that cyclizations of this type can be brought about despite an unfavourable equilibrium between ring-opened and ring-closed Grignard intermediates, due to the possibility of conversion of an alkylmagnesium halide into a thermodynamically more stable alkoxymagnesium halide from proposed ring-closed Grignard intermediates.