Ring-Closing Strategy Utilizing Nitrile α-Anions: Chiral Synthesis of (+)-Norchrysanthemic Acid and Expeditious Asymmetric Total Synthesis of (+)-Grandisol
Ring-Closing Strategy Utilizing Nitrile α-Anions: Chiral Synthesis of (+)-Norchrysanthemic Acid and Expeditious Asymmetric Total Synthesis of (+)-Grandisol
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DOI：
10.1002/ejoc.201801160
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发表时间：
2018-11-25
影响因子：
2.8
通讯作者：
Tanabe, Yoo
中科院分区：
文献类型：
--
作者：
Fujiwara, Tetsuya;Okabayashi, Tomohito;Tanabe, Yoo
本文报道了以腈的α位碳负离子（腈的α-阴离子）为手性关环剂，合成了（1 R，3R）-（1 Z）-降胆甾酸和（+）-grandisol两种不同的小环烷烃。(i)（1 R，3R）-（1 Z）-降冰片酸，一种含有环丙烷结构的合成拟除虫菊酯的高效成分，由易得的衍生自3-甲基-丁-2-烯-1-醇的（S）-环氧化物经7步合成，总收率23%，ee> 98%。该顺序涉及使用（S）-3-甲基-丁-2-烯-1-醇的腈α-阴离子反式选择性地形成环丙烷。甲磺酰氧基腈为关键步骤。本发明的手性合成进行了有效的立体控制的手性在1，3-位上的环丙烷和Z-几何的丙烯基。(ii)（+）-Grandisol是一种具有特征环丁烷结构的昆虫性信息素，由市售的环丙基甲基酮（路线A）或由市售的3-氰基丙基溴化锌和1-溴-1-甲基丙烯（路线B）经10步或8步以6%或8%的总产率合成，该序列涉及三取代烯烃的Shi不对称环氧化和使用手性环氧腈的腈α-阴离子的具有干净S（N）2立体转化的直接Stork型不对称环丁烷形成。本发明的方法是从非手性化合物开始的第二种不对称全合成。
Chiral syntheses of two distinct small cycloalkanes, (1R,3R)-(1Z)-norchrysanthemic acid and (+)-grandisol, were performed by characteristic ring-closing methodologies using carbanions at the alpha-position of nitriles (nitrile alpha-anions). (i) (1R,3R)-(1Z)-Norchrysanthemic acid, a highly potent ingredient of synthetic pyrethroid containing a cyclopropane structure, was synthesized from readily available (S)-epoxide derived from 3-methyl-but-2-en-1-ol in 7 steps in 23 % overall yield and with > 98 % ee. This sequence involves a trans-selective cyclopropane formation using the nitrile alpha-anion of (S)-3-mesyloxynitrile as the key step. The present chiral synthesis was performed with effective stereocontrol of both the chirality in the 1,3-positions on the cyclopropane and the Z-geometry of the propenyl group. (ii) (+)-Grandisol, an insect sex pheromone possessing a characteristic cyclobutane structure, was synthesized from commercially available cyclopropyl methyl ketone (route A) or from commercially available 3-cyanopropylzinc bromide and 1-bromo-1-methylpropene (route B) in 10 or 8 steps in 6 % or 8 % overall yield and with 80 % ee. This sequence involves a Shi asymmetric epoxidation of a trisubstituted olefin and a straightforward Stork-type asymmetric cyclobutane formation with clean S(N)2 stereoinversion using the nitrile alpha-anion of the chiral epoxynitrile. The present expedient method is the second asymmetric total synthesis starting from achiral compounds.