Heck reaction of ortho-substituted iodobenzenes with α,β-unsaturated nitriles as a key step in the synthesis of tetrahydro-2-benzazepines and hexahydro-3-benzazocines

被引：14

作者：

Hasebein, Peer ^{[1
]}

Aulinger, Katharina ^{[1
]}

Schepmann, Dirk ^{[1
]}

Wuensch, Bernhard ^{[1
]}

机构：

[1] Univ Munster, Inst Pharmazeut & Med Chem, D-48149 Munster, Germany

来源：

TETRAHEDRON | 2013年 / 69卷 / 23期

关键词：

Tetrahydro-2-benzazepines; Hexahydro-3-benzazocines; Heck reaction; Reductive cyclization; sigma(1) Receptor ligands; Structure-sigma(1) affinity relationships; NMDA RECEPTOR ANTAGONISTS; ASYMMETRIC-SYNTHESIS; SIGMA(1) RECEPTOR; 1-SUBSTITUTED TETRAHYDRO-3-BENZAZEPINES; RING HOMOLOGS; LIGANDS; AFFINITY; DERIVATIVES; ANALOGS; AGONIST;

D O I：

10.1016/j.tet.2013.04.017

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A novel strategy is reported for the synthesis of tetrahydro-2-benzazepines 2 and hexahydro-3-benzazocines 3 comprising a Heck reaction of ortho-substituted iodobenzenes 6 and 14 with alpha,beta-unsaturated nitriles. Hydrogenation of the resulting alpha,beta-unsaturated nitriles 7, 11, 15, and 16 was followed by reductive cyclization. It was shown that the formation of 2-benzazepines was faster than the formation of 3-benzazocines, which was explained by the higher stability of the aliphatic dimethyl acetals in 17 and 18. The tetrahydro-2-benzazepine 2d with an N-butyl residue reveals very high sigma(1) affinity with a K-i-value of 2.0 nM. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4552 / 4562

页数：11

共 17 条

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