title: Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.
abstract: Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non-measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1-alkanols, with ≥99 % enantiomeric excess (ee), by the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu-catalyzed cross-coupling reactions. ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected ω-alkene-1-ols protocols were applied to the synthesis of both (R)- and (S)-difunctional intermediates with 80-90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1-alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium-labeled groups by Cu-catalyzed cross-coupling reactions without epimerization.
authors.affiliation: Herbert C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084 (USA), Fax: (+1) 765-494-0239.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.forename: Akimichi
authors.initials: A
authors.lastname: Oda
authors.forename: Ei-ichi
authors.initials: E
authors.lastname: Negishi
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry*; D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry; D000535:Aluminum / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry; D013237:Stereoisomerism; D015040:Zirconium / Q000737:chemistry*
chemical_list: D000438:Alcohols; D000473:Alkanes; D000475:Alkenes; D020005:Propanols; C006463:allyl alcohol; D003300:Copper; D015040:Zirconium; D000535:Aluminum
keywords: ZACA reaction; asymmetric catalysis; chiral isotopomers; cross-coupling; cryptochirality