Synthesis of Tetrahydroisoquinoline Alkaloids and Related Compounds through the Alkylation of Anodically Prepared α-Amino Nitriles
Synthesis of Tetrahydroisoquinoline Alkaloids and Related Compounds through the Alkylation of Anodically Prepared α-Amino Nitriles
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DOI：
10.1021/acs.joc.6b01419
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发表时间：
2016-08-05
影响因子：
3.6
通讯作者：
Hurvois, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Benmekhbi, Lotfi;Louafi, Fadila;Hurvois, Jean-Pierre
由手性六氟磷酸盐异喹啉鎓（-）-8b以两个单独的步骤方便地制备α-氨基腈2a，包括阳极氰化作为活化THIQ核的sp（3）C1-H键的有效手段。2a的锂化在-80 ° C下在LDA存在下在THE中进行以产生稳定的α-氨基碳负离子，其缩合在多种烷基卤化物上。在NaBH_4作为氢化物给体存在下，在乙醇中对得到的季α-氨基腈进行立体选择性还原脱氰，在除去手性辅助基团后，以高达97：3的摩尔比得到N-Boc-1-烷基-THIQs（+）-10a-g。THIQ（+）-If的ORTEP视图检查显示，新创建的立体中心具有绝对S构型。同样，在四个后处理步骤中以总收率63%从α-氨基腈（+）-2b合成（-）-木品宁。在该方法中，结晶（-）-去甲劳丹诺新与1当量（-）-N-乙酰基-L-亮氨酸的对映体富集混合物（90：10），得到亮氨酸盐（+）-13（99：1dr）。类似地，（+）-salsolidine以99：1 er从其（-）-DBTA盐（-）-12置换，这通过在硫代膦酸（+）-14作为手性溶剂化剂存在下的质子和碳NMR光谱测定。
alpha-Amino nitrile 2a was conveniently prepared in two individual steps from chiral hexafluorophosphate salt isoquinolinium (-)-8b including anodic cyanation as an efficient means to activate the sp(3) C1-H bond of the THIQ nucleus. The lithiation of 2a was carried out in THE at -80 degrees C in the presence of LDA to produce a stable alpha-amino carbanion which was condensed on a large variety of alkyl halides. The resulting quaternary alpha-amino nitriles were subjected to a stereoselective reductive decyanation in ethanol in the presence of NaBH4 as the hydride donor to yield N-Boc-1-alkyl-THIQs (+)-10a-g in up to 97:3 er's after removal of the chiral auxiliary group. Examination of the ORTEP view of THIQ(+)-If revealed that the newly created stereogenic center had an absolute S configuration. Likewise, (-)-xylopinine was synthesized in four workup steps in an overall 63% yield from alpha-amino nitrile (+)-2b. In this process, crystallization of an enantioenriched mixture (90:10) of (-)-norlaudanosine with 1 equiv of (-)-N-acetyl-L-leucine afforded the leucinate salt (+)-13 (99:1 dr). Similarly, (+)-salsolidine was displaced from its (-)-DBTA salt (-)-12 in 99:1 er, which was determined by proton and carbon NMR spectroscopy in the presence of thiophosphinic acid (+)-14 as the chiral solvating agent.