Diastereoselective conjugate addition to chiral alpha,beta-unsaturated carbonyl systems in aqueous media: an enantioselective entry to alpha- and gamma-hydroxy acids and alpha-amino acids.
The stereoselectivity of the ultrasonically induced zinc--copper conjugate addition of iodides to chiral alpha,beta-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to methylenedioxolanone 1 and methyleneoxazolidinone 2 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 gamma,delta-dioxolanyl-alpha,beta-unsaturated esters 3-5 also proceeds with good yields (51-99 %). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer 3 gives high diastereoselectivity, while the reactions with the E isomer 4 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 alpha- and gamma-hydroxy acids and alpha-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.
Suárez
Rosa M
RM
Departamento de Química Fundamental Universidade da Coruña 15071 A Coruña, Spain.
Pérez Sestelo
José
J
Sarandeses
Luis A
LA
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D006880:Hydroxy Acids / Q000138:chemical synthesis* / Q000737:chemistry; D023303:Oxazolidinones / Q000737:chemistry; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
D000596:Amino Acids; D004952:Esters; D006847:Hydrocarbons, Iodinated; D006880:Hydroxy Acids; D023303:Oxazolidinones; D014867:Water; D003300:Copper; D015032:Zinc