New Cyclopropyl Building Blocks for Organic Synthesis, 21. Diels‐Alder Reactions of Methyl 2‐Chloro‐2‐cyclopropylideneacetate with Electron‐Rich Dienes: Synthesis of Potential Intermediates for Illudin M

Abstract

Abstract 1‐Ethoxy‐ ( 8a ) and 1‐(trimethylsilyloxy)‐1,3‐pentadiene ( 8b ) cycloadded to 2‐chloro‐2‐cyclopropylideneacetate 6 to give low yields of endo / exo ‐ 9a and ‐9b , respectively. On the other hand, furans 5a‐d added 6 (5b and 5d reacted regioselectively) to afford mixtures of the corresponding [4 + 2] cycloadducts endo ‐ 11a‐d and exo‐ 11a ‐ d in good to high yields. 2‐Methyl‐5‐(trimethylsilyloxy)furan ( 5e ) yielded a mixture of the four cycloadducts endo / exo ‐ 11e and endo / exo ‐ 12e , which upon attempted purification on silica gel underwent facile hydrolysis to give bicyclic hemiacetals endo / exo ‐ 13 and 4‐hydroxycyclo‐2‐hexen‐1‐ones endo / exo ‐ 14 , respectively. Similarly endo / exo ‐ 11f , and endo / exo ‐ 12f , obtained from 2‐methoxy‐5‐methylfuran ( 5f ) and 6 , upon hydrolysis in the presence of silica gel gave endo / exo ‐ 13 and endo / exo ‐ 14 respectively. The structures of endo ‐ 14 and exo ‐ 12f were established by X‐ray crystallography. In the presence of florisil, the epoxides endo ‐and exo ‐ 16 were formed from trimethylsilyloxy‐substituted cycloadducts endo / exo ‐ 11e . Selective reduction of the α‐chlorocarboxylate functionality in the cycloadducts endo ‐ 11a ‐ d,f with LiBH 4 , followed by base‐catalyzed cyclization of the resulting chlorohydrins endo ‐ 21a ‐ d , f yielded the corresponding epoxides endo ‐ 22a ‐ d,f in 22–73% overall yield. Under identical conditions, the cycloadducts exo ‐ 11a ‐ f could not be reduced to the corresponding chlorohydrins exo ‐ 21a ‐ f . Regioselective reduction of the acetal epoxide endo ‐ 22f to the tertiary alcohol endo ‐ 23f was achieved with sodium dihydrobis(2‐methoxyethoxy)aluminate (Red‐Al ® ). On stirring with moist silica gel, the bicyclic acetals endo ‐ 22d,f and endo ‐ 23f cleanly hydrolysed to the highly substituted spiro[2.5]oct‐6‐en‐5‐ones endo ‐ 24d,f (26 and 24% overall yields, respectively, in four steps from 5d,f and 6 ) and endo ‐ 25f , respectively (23% overall yield in five steps from 5f and 6 ).