Asymmetric Alkylation ofIminium Ion Based on Control of Dynamic Stereochemistry

本文研究了α-甲氧基哌啶和N-保护哌啶电化学合成β，γ-不饱和哌啶的亚胺鎓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，γ-不饱和α-甲氧基-N-4-甲氧基苯甲酰基哌啶2与丙二酸二甲酯反应，得到α-取代哌啶，对映选择性为50%ee 2.以丙二酸二苯酯为亲核试剂，与2反应，得到了高对映选择性的取代哌啶。3.乙酰乙酸甲酯与α-甲氧基-N-4-甲氧基苯甲酰基哌啶1在0℃下反应，合成了65%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，以中等的对映选择性（45%ee）得到γ-取代哌啶。在此情况下，MOC基团最适合作为N-保护基。5.这些产物可以转化为光学活性的（2-哌啶基）乙酸和辛可洛酮酸甲酯，它们是合成生物活性化合物的关键中间体。

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.