title: 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.
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.
authors.affiliation: H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.forename: Ching-Tien
authors.initials: CT
authors.lastname: Lee
authors.forename: Guangwei
authors.initials: G
authors.lastname: Wang
authors.forename: Ei-ichi
authors.initials: E
authors.lastname: Negishi
mesh_terms: D000107:Acetylation; D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008049:Lipase / Q000378:metabolism; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D015040:Zirconium / Q000737:chemistry*
chemical_list: D000438:Alcohols; D000475:Alkenes; D010165:Palladium; D003300:Copper; D015040:Zirconium; D008049:Lipase
keywords: asymmetric synthesis; cross-coupling; enzyme catalysis; homogeneous catalysis