endo/exo Stereoselectivity in Diels-Alder Reactions of alpha,beta-Dialkylated Conjugated Enals to Cyclic 1,3-Dienes: Intermediates in the Synthesis of (-)-beta-Santalol and Its Analogs

摘要

Highly exo-selective [4+2] cycloadditions of cyclopenta-1,3-diene 2a to ,-dialkyl conjugated enals 5 are compared with the analogous endo-favored DielsAlder reaction of cyclohexa-1,3-diene 7. The exo-stereoselectivity is lower in the homologous case of methylcyclopenta-1,3-diene 9. This diastereoselectivity is discussed either in terms of a retro-homo-DielsAlder reaction, associated with thermodynamic control, or with respect to either a competing hetero-DielsAlder/Claisen or Cope domino pathway, or retro-Claisen/retro-hetero-DielsAlder of the endo-homo-cycloadducts. These hypothetical mechanisms have been examined by DFT calculations at the MPW1K(CH2Cl2)/6-31+G** level of theory for the AlCl3-mediated cycloadditions of 5d to 2a and 7. Application of Corey's methodology to the -halogeno--methyl-substituted dienophiles 5a and 5b allowed an enantioselective preparation of known and useful intermediates for the synthesis of either the naturally occurring (-)--santalol or its potentially olfactive structural analogs.