Evolution of Routes for Asymmetric Total Synthesis of Cyclocitrinol Enabled by Type Ⅱ [5+2] Cycloaddition

• 作者: Jianlei Wu Junyang Liu Jian-Hong Fan Zhi-Dong Xie Hukun Qin Chuang-Chuang Li
• 来源期刊: 中国化学（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Concise Reports
• 页码范围: 1247-1254
• 页数: 8页
• 语种: 英文
• DOI: 10.1002/cjoc.202000698

摘要

Main observation and conclusion The asymmetric total synthesis of an unusual C25 steroid containing a unique bicyclo[4.4.1]undecene A/B ring system,resulting in the synthesis of cyclocitrinol (1) and its isomer Δ8,14-cyclocitrinol (38),is reported.Initial attempts to construct the synthetically challenging bicyclo[4.4.1]undecene A/B ring system using a type Ⅱ [5+2] cycloaddition showed that a chiral substituent at the allylic position of the alkene (C6,cyclocitrinol numbering) controlled the stereoselective outcome of the cycloaddition reaction.Late-stage migration of the tetrasubstituted C8-C14 double bond in A8,14-cydocitrinol (38) to obtain cyclocitrinol (1) proved challenging,inspiring an alternative approach.The chiral β-CH2OR group on the allylic substituent at C6 played a pivotal role both in controlling the diastereoselectivity of the type Ⅱ [5+2] cycloaddition and retaining the C6 substituent under lithium-amine conditions.