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Evolution of Routes for Asymmetric Total Synthesis of Cyclocitrinol Enabled by Type II [5+2] Cycloaddition †
Author(s) -
Wu Jianlei,
Liu Junyang,
Fan JianHong,
Xie ZhiDong,
Qin Hukun,
Li ChuangChuang
Publication year - 2021
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.202000698
Subject(s) - cycloaddition , chemistry , substituent , allylic rearrangement , stereochemistry , bicyclic molecule , alkene , stereoselectivity , double bond , total synthesis , amine gas treating , ring (chemistry) , medicinal chemistry , organic chemistry , catalysis
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 Δ 8,14 ‐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 Δ 8,14 ‐cyclocitrinol (38) to obtain cyclocitrinol (1) proved challenging, inspiring an alternative approach. The chiral β‐CH 2 OR 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.