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Development of A Chiral Homoenolate Equivalent which Reacts Selectively with Imines

开发与亚胺选择性反应的手性高烯醇等价物

基本信息

批准号：
12650847
负责人：
OKAMOTO Sentaro
金额：
$ 2.37万
依托单位：
TOKYO INSTITUTE OF TECHNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12650847/
关键词：
low valent titanium allyl homoenolate imine asymmetric synthesis γ-amino acid anti-HIV 低原子化

项目摘要

A chiral allyltitanium compound, prepared in situ by the reaction of optically active acrolein 1,2-dicyclohexylethylene acetal with a divalent titanium reagent, Ti(O-i-Pr)_4/2i-PrMgCl, reacts with a variety of acyclic and cyclic imines in a regiospecific way to afford cc-addition products as a mixture of the E- and Z-isomers in good combined yield, where the former is predominant in a ratio of 92:8 to >95:5. The mixture of (E)- and (Z)-adducts and pure (E)-adducts which could be isolated in several cases were respectively converted to the corresponding β-amino esters to confirm the absolute configuration and enantiomeric purity. The ee of the newly-formed asymmetric center is more than 78 % for the mixture of (E)- and (Z)-addition products and more than 96 % for pure (E)-isomer. By taking advantage of the versatility of the vinyl ether moiety in reaction products, optically active γ-amino aldehydes, γ-amino aldehyde acetals, y-amino acids, β-amino esters, andpyrrolidinoisoquinolines were readily prepared. In the reaction of the allyltitanium with optically active cc-silyloxyimine, remarkable double stereodifferentiation was observed; thus, the reaction of the allyltitanium derived from (S,S)- or (R,R)-1,2-dicyclohexylethylene acetal provided syn- and anti-adducts in a ratio of 55 : 45 or 0 : 100 respectively. Meanwhile, the stereochemistry of the product in the reaction with β-silyloxyimine was controlled mainly by the allyltitanium. The reaction could be effectively applied to prepare 4-amino-6-hydroxypentadecanal dimethyl acetal, a key intermediate for the synthesis of batzelladine D.

由光学活性的丙烯醛1，2-二环己基乙烯缩醛与二价钛试剂Ti（O-i-Pr）_4/2 i-PrMgCl原位反应制备的手性烯丙基钛化合物，与各种无环和环状亚胺以区域特异性方式反应，以良好的合并产率得到E-和Z-异构体的混合物形式的α-加成产物，其中前者以92：8至>95：5的比例占主导地位。将（E）-和（Z）-加合物的混合物和在几种情况下可以分离的纯（E）-加合物分别转化为相应的β-氨基酯以确定绝对构型和对映体纯度。对于（E）-和（Z）-加成产物的混合物，新形成的不对称中心的ee大于78%，而对于纯的（E）-异构体，新形成的不对称中心的ee大于96%。利用乙烯基醚在反应产物中的多功能性，可以方便地制备光学活性的γ-氨基醛、γ-氨基醛缩醛、γ-氨基酸、β-氨基酯和吡咯烷基异喹啉。在烯丙基钛与光学活性α-甲硅烷基氧基亚胺的反应中，观察到显著的双立体分化;因此，衍生自（S，S）-或（R，R）-1，2-二环己基乙烯缩醛的烯丙基钛的反应分别以55：45或0：100的比例提供顺式加合物和反式加合物。与β-硅氧亚胺反应产物的立体化学主要受烯丙基钛的控制。该反应可有效地用于合成巴茨拉定D的关键中间体4-氨基-6-羟基十五醛二甲缩醛的合成。