title: Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd-catalyzed cross-coupling.
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 γ- 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 ω-alkene-1-ols produced both (R)- and (S)-α,ω-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 α,ω-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 γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-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.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Oda
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamada
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907 negishi@purdue.edu.
authors.forename: Ei-ichi
authors.initials: E
authors.lastname: Negishi
mesh_terms: D000107:Acetylation; D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000475:Alkenes / Q000737:chemistry*; D017607:Aluminum Compounds / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008049:Lipase / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D015040:Zirconium / Q000737:chemistry*
chemical_list: D000438:Alcohols; D000475:Alkenes; D017607:Aluminum Compounds; D010165:Palladium; D002244:Carbon; D003300:Copper; D015040:Zirconium; D008049:Lipase