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

Authors

  • Dr. Shiqing Xu,

    1. H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084 (USA), Fax: (+1) 765-494-0239
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  • Dr. Ching-Tien Lee,

    1. H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084 (USA), Fax: (+1) 765-494-0239
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  • Dr. Guangwei Wang,

    1. H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084 (USA), Fax: (+1) 765-494-0239
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  • Prof. Dr. Ei-ichi Negishi

    Corresponding author
    1. H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084 (USA), Fax: (+1) 765-494-0239
    • H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084 (USA), Fax: (+1) 765-494-0239

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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 (), 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 or 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.

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