080407-羰基反应2.ppt

Directed reductions of b-hydroxyketones Directed reductions of b-hydroxyketones: rationale for high selectivity Evans, Chapman, Carreira, JACS 110, 3560 (1988) Remote Heteroatom Effects in Carbonyl Addition Definition of Terms Felkin-Ahn model Felkin product: commonly accepted term for the major carbonyl addition product predicted by the Felkin-Anh model; also predicted by Cram and Karabatsos for steric cases, Cornforth for a-heteroatom (non-chelating) cases Cram, The Morning of Asymmetric Induction Crams Rule: “….The entering group from the least hindered side of the double bond when the rotational conformation of the C–C bond is such that the double bond is flanked by the two least bulky groups attached to the adjacent asymmetric center. Cram’s Rule: Features and Liability Cram’s Rule: Prediction of the product Cram Assumed “Me NH3Cl due to the amino groups formation of a non-rigid more adaptable ion pair” Cram’s Rule: Prediction of the product MeNHMgBr? Methyl has greater effective bulk than OH. Cram cites A-values of Winstein, who compares the relative tendency of groups to occupy the equatorial position on a cyclohexane ring. CH3 OSO2C6H4CH3-p OCOCH3 OH Cram’s Rule in 1959: Prediction of the product---Explanation Cram’s Rule in 1959: Chelate Model The open-chain model applies to systems which contain only groups attached to asymmetric carbon of the starting material which are incapable of complexing with organometallic reagents (J. Am. Chem. Soc. 1959, 81, 2748 ) Cornforth: 1959 Argument based on importance of polarization in transition state, and evidence of selectivity in a-chlorocyclohexanone additions where the dipoles are antiparallel, the polarization of the carbonyl group would be easiest, thereby lowering transition state energy a modification of Crams rule for electronegative, non-chelating a-substituents X Cornforth Role--features J. Chem. Soc. 1959, 112 Karabatsos’ rule: Features energy difference (DDH°) between interactions of RM←→O and R