Enantioselective Organocatalytic Formal 3 + 3-Cycloaddition of α,β-Unsaturated Aldehydes and Application to the Asymmetric Synthesis of (−)-Isopulegol Hydrate and (−)-Cubebaol

reaction: see text The first highly enantioselective organocatalyzed carbo 3 + 3 cascade cycloaddition of alpha,beta-unsaturated aldehydes is reported. Using this methodology, crotonaldehyde is converted to 6-hydroxy-4-methylcyclohex-1-enecarbaldehyde, which is used in the synthesis of (-)-isopulegol hydrate, (-)-cubebaol, and p-tolualdehyde as well as (-)-6-hydroxy-4-methyl-1-cyclohexene-1-methanol acetate, an intermediate in the total synthesis of lycopodium alkaloid magellanine. Other alpha,beta-unsaturated aldehydes give rise to chiral cyclohexadienes via formal 4 + 2 reactions.