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Asymmetric Alkylation ofIminium Ion Based on Control of Dynamic Stereochemistry

基于动态立体化学控制的亚胺离子不对称烷基化

基本信息

批准号：
15550094
负责人：
ONOMURA Osamu
金额：
$ 2.43万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15550094/
关键词：
iminium ion asymmetric alkylation copper bisoxazoline dynamic complex optically active piperidine regioselective

项目摘要

Catalytic asymmetric alkylation of iminium ions, which were generated from α-methoxylated piperidines and β,γ-unsaturated piperidines electrochemically prepared from N-protected piperidines, has been developed.1.In the presence of a catalytic amount of Cu(OTf)_2 and chiral bisoxazoline ligand, at room temperature the reaction of β,γ-unsaturated α-methoxy-N-4-methoxybenzoylpiperidine 2 and dimethyl malonate gave a-substituted piperidine in moderate enantioselectivity (50%ee).2.Using diphenyl malonates as nucleophiles in the reactions with 2 gave orsubstituted piperidine with high enantioselectivities (up to 95%ee).3.Methyl acetoacetate reacted with α-methoxy-N-4-methoxybenzoylpiperidine 1 at 0℃ to give α-substituted piperidine in 65%ee. Also, the reaction of methyl acetoacetate and 2 at -20℃ afforded α-substituted piperidine in 80%ee.4.The reaction of β-ethyl-β,γ-unsaturated-α-methoxypiperidine and methyl acetoacetate proceeded at room temperature to give γ-substituted piperidine in moderate enantioselectivity (45%ee). In this case MOC group was the most suitable for N-protecting group.5.These products could be transformed into optically active (2-piperidyl)acetic acid and methyl cincholoiponate, which are key intermediates for syntheses of bioactive compounds.

以α-甲氧基化哌啶和N-保护哌啶电化学制备β,γ-不饱和哌啶为原料，开发了亚胺离子的催化不对称烷基化反应。1.在催化量的Cu(OTf)_2和手性双恶唑啉配体存在下，在室温下反应 β,γ-不饱和α-甲氧基-N-4-甲氧基苯甲酰哌啶2和丙二酸二甲酯生成具有中等对映选择性(50%ee)的α-取代哌啶。2.使用丙二酸二苯酯作为亲核试剂与2反应生成具有高对映选择性(可达 95%ee).3.乙酰乙酸甲酯与α-甲氧基-N-4-甲氧基苯甲酰哌啶1在0℃下反应，得到α-取代哌啶，65%ee。乙酰乙酸甲酯与2在-20℃反应，得到80%ee的α-取代哌啶。4。β-乙基-β,γ-不饱和-α-甲氧基哌啶与乙酰乙酸甲酯在室温下反应，得到中等对映选择性的γ-取代哌啶(45%ee)。在这种情况下，MOC基团是最适合的N-保护基团。5.这些产物可以转化为光学活性的(2-哌啶基)乙酸和辛胆酸甲酯，它们是合成生物活性化合物的关键中间体。