Lithiation Substitution of Unprotected Benzyltetrazoles

被引：4

作者：

Wong, Jeff Y. F. ^{[1
]}

Lewandowska, Agnieszka ^{[1
]}

Trowse, Benjamin R. ^{[1
]}

Barker, Graeme ^{[1
]}

机构：

[1] Heriot Watt Univ, Inst Chem Sci, Edinburgh EH14 4AS, Midlothian, Scotland

来源：

ORGANIC LETTERS | 2019年 / 21卷 / 17期

基金：

英国工程与自然科学研究理事会;

关键词：

GROWTH-HORMONE SECRETAGOGUE; METALATION; LOSARTAN; DESIGN; ACIDS;

D O I：

10.1021/acs.orglett.9b02633

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

1H-Tetrazoles occupy an important role in modern medicinal chemistry, but few methods for their modification exist. Many extant protocols require the use of a difficult to remove N-alkyl-protecting group, precluding the products from use as carboxylate bioisosteres, the major role of tetrazoles in pharmaceuticals. We herein report a convenient, protecting-group-free lithiation-substitution protocol for benzylic tetrazoles. Metalation with n-BuLi at 0 degrees C followed by electrophilic trapping gave a range of alpha-functionalized benzyltetrazoles in up to 91% yield.

引用

页码：7069 / 7072

页数：4

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