Formal Highly Enantioselective Organocatalytic Addition of Alkyl Anions to α,β-Unsaturated Aldehydes: Application to the Synthesis of Isotope-Enantiomers

A practical and powerful methodology that constitutes an organocatalytic alternative for organometallic 1,4-additions was developed. In a vial, bis(phenylsulfonyl)methane and catalyst V were added to toluene. Next, unsaturated aldehyde 1a was added and the reaction mixture was stirred at 4°C overnight. The crude product was purified by column chromatography to afford the final compound 4a. The stereochemical outcome of the reaction can be easily rationalized by the mechanistic proposal. Thus, efficient shielding of the Re-face of the chiral iminium intermediate 15 by the bulky aryl groups of V leads to stereoselective Si-facial nucleophilic conjugate attack on the β-carbon of 15. This mechanism is in accordance with those proposed for other amine-catalyzed reactions between nucleophiles and enals.