The Origin of High Stereoselectivity in Di-tert-butylsilylene-Directed α-Galactosylation

J Org Chem. 2016 Oct 7;81(19):9086-9104. doi: 10.1021/acs.joc.6b01685. Epub 2016 Sep 29.

Abstract

The origin of the high α(1,2-cis)-stereoselectivity in the reaction of galactosyl and galactosaminyl donors with a di-tert-butylsilylene (DTBS) group with several nucleophiles has been elucidated by means of experimental and computational approaches. DTBS overcomes any other cyclic protecting groups examined to date and the β(1,2-trans)-directing effect due to the neighboring participation by CO groups at C2. Requirements for the α(1,2-cis)-stereoselectivity are as follows: (1) generation of an oxocarbenium ion; (2) a galacto-type glycosyl donor with a cyclic protecting group bridging O4 and O6 to form a six-membered ring; (3) through-space electron donation from O4 and O6 into the empty p-orbital of the anomeric carbon to stabilize the oxocarbenium intermediate; (4) steric hindrance due to bulky alkyl substituents on the cyclic protecting group to prevent nucleophilic attack from the β-face; and (5) a 4,6-O-silylene structure. Furthermore, it was found that the strong stereodirecting effect of the DTBS group was unique and specific among the various cyclic protecting groups examined.

Publication types

  • Research Support, Non-U.S. Gov't