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

The first highly enantioselective organocatalyzed carbo [3 + 3] cascade cycloaddition of α,β-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 α,β-unsaturated aldehydes give rise to chiral cyclohexadienes via formal [4 + 2] reactions.