Enantioselective Preparation of β,β-Disubstituted α-Methylenepropionates by MAO Promotion of the Zinc Schlenk Equilibrium

摘要

In the copper-catalyzed reactions of organometallic nucleophiles (RM) with allylic halides R1CHCR2CH2X, two reaction pathways are possible: either direct SN2 displacement at the α carbon or SN2 displacement γ to the leaving group. Recently, considerable progress has been made towards the development of asymmetric processes that result from copper-catalyzed SN2 addition of organozinc or Grignard reagents.[1] These studies have generally used allylic halides that lack functional groups and have focused largely on (E)-cinnamyl halides or equivalent phosphate esters (R1=Ph, R2=H). Reactions with ester-functionalized electron-deficient allylic halides (R2=CO2R, R1=various, 1) would offer rapid access to highly useful chiral β,β-disubstituted α-methylenepropionates 2 (see Table 1). Highly selective additions of ZnR2 to the regioisomers of 1 have been demonstrated,[2] but the former substrates themselves have proved highly resistant to effective asymmetric catalysis.[3]