Highly enantioselective synthesis of -, -, and -chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd-catalyzed cross-coupling. Academic Article uri icon

abstract

  • Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (99% ee) and catalytic synthesis of various - and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)-Cu- or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert-butyldimethylsilyl (TBS)-protected -alkene-1-ols produced both (R)- and (S)-,-dioxyfunctional intermediates (3) in 80-88% ee, which were readily purified to the 99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These ,-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of -, -, and -chiral 1-alkanols of 99% ee. The MNP ester analysis has been applied to the determination of the enantiomeric purities of - and -chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 12.5

author list (cited authors)

  • Xu, S., Oda, A., Kamada, H., & Negishi, E.

citation count

  • 18

complete list of authors

  • Xu, Shiqing||Oda, Akimichi||Kamada, Hirofumi||Negishi, Ei-ichi

publication date

  • January 2014