Diastereoselective conjugate addition to chiral α,β-unsaturated carbonyl systems in aqueous media: an enantioselective entry to α- and γ-hydroxy acids and α-amino acids.

Suárez, R. M.; Pérez Sestelo, J.; Sarandeses, L. A.


Chem. Eur. J. 2003, 9, 4179–4187 (DOI: 10.1002/chem.200304790).

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The stereoselectivity of the ultrasonically induced zinc–copper conjugate addition of iodides to chiral α,β-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to a methylenedioxolanone and to a methyleneoxazolidinone to afford the 1,4-addition products in good yields (38–95%) and with high diastereomeric excess (44–90% de). The 1,4-addition to chiral γ,δ-dioxolanyl-α,β-unsaturated esters also proceeds with good yields (51–99%). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer gives high diastereoselectivity, while the reactions with the E isomer are nonstereoselective. The reaction proceeds with excellent chemoselectivity and allows the use of iodides bearing ester, hydroxy, and amino groups. Since the 1,4-addition products can be readily hydrolyzed, this methodology constitutes a novel entry for the enantioselective synthesis of α-and γ-hydroxy acids and α-amino acids in aqueous media. The results obtained support the radical mechanism proposed by Luche, and represent one of the few examples of a radical stereoselective conjugate addition in aqueous medium.