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Widely Applicable Synthesis of Enantiomerically Pure Tertiary Alkyl‐Containing 1‐Alkanols by Zirconium‐Catalyzed Asymmetric Carboalumination of Alkenes and Palladium‐ or Copper‐Catalyzed Cross‐Coupling
Author(s) -
Xu Shiqing,
Lee ChingTien,
Wang Guangwei,
Negishi Eiichi
Publication year - 2013
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201300311
Subject(s) - zirconium , catalysis , alkyl , palladium , copper , chemistry , coupling (piping) , organic chemistry , polymer chemistry , materials science , metallurgy
Abstract A highly enantioselective and widely applicable method for the synthesis of various chiral 2‐alkyl‐1‐alkanols, especially those of feeble chirality, has been developed. It consists of zirconium‐catalyzed asymmetric carboalumination of alkenes (ZACA), lipase‐catalyzed acetylation , and palladium‐ or copper‐catalyzed cross‐coupling . By virtue of the high selectivity factor ( E ) associated with iodine, either ( S )‐ or ( R )‐enantiomer of 3‐iodo‐2‐alkyl‐1‐alkanols ( 1 ), prepared by ZACA reaction of allyl alcohol, can be readily purified to the level of ≥99 % ee by lipase‐catalyzed acetylation . A variety of chiral tertiary alkyl‐containing alcohols, including those that have been otherwise difficult to prepare, can now be synthesized in high enantiomeric purity by Pd‐ or Cu‐catalyzed cross‐coupling of (S)-1 or (R)-2 for introduction of various primary, secondary, and tertiary carbon groups with retention of all carbon skeletal features. These chiral tertiary alkyl‐containing alcohols can be further converted into the corresponding acids with full retention of the stereochemistry. The synthetic utility of this method has been demonstrated in the highly enantioselective (≥99 % ee ) and efficient syntheses of ( R )‐2‐methyl‐1‐butanol and ( R )‐ and ( S )‐arundic acids.