Department of Applied Bio-organic Chemistry, Faculty of Applied Biological Sciences, Gifu University , 1-1 Yanagido, Gifu 501-1193, Japan.
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu 501-1193, Japan.
J Org Chem. 2016 Oct 7;81(19):9086-9104. doi: 10.1021/acs.joc.6b01685. Epub 2016 Sep 29.
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.
通过实验和计算方法，阐明了带有几个亲核试剂的二特丁基硅基（DTBS）基团的半乳糖基和半乳糖胺基供体与几种亲核试剂反应中高α(1,2-顺式）立体选择性的起源。DTBS 克服了迄今为止检查过的任何其他环状保护基，并且由于 CO 基团在 C2 处的相邻参与而具有β(1,2-反式）导向效应。对 α(1,2-顺式）立体选择性的要求如下：(1) 生成氧杂碳正离子；(2) 具有环状保护基的半乳糖型糖基供体，该保护基将 O4 和 O6 桥接在一起形成六元环；(3) 通过空间从 O4 和 O6 向糖的端基碳原子的空 p 轨道进行电子供体，以稳定氧杂碳正离子中间体；(4) 环状保护基上大体积烷基取代基引起的空间位阻，防止亲核攻击从β-面进行；以及(5) 4,6-O-硅基烯结构。此外，还发现 DTBS 基团的强立体定向效应在检查的各种环状保护基中是独特且特定的。
