Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.
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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 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-insitu iodinolysis of allyl alcohol and ZACA-insitu oxidation of TBS-protected -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.
