Lithiation Substitution of Unprotected Benzyltetrazoles

Jeff Y. F. Wong; Agnieszka Lewandowska; Benjamin Trowse; Graeme Barker

doi:10.1021/acs.orglett.9b02633

Lithiation Substitution of Unprotected Benzyltetrazoles

Jeff Y. F. Wong, Agnieszka Lewandowska, Benjamin Trowse, Graeme Barker

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Abstract

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 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.

Original language	English
Pages (from-to)	7069-7072
Number of pages	4
Journal	Organic Letters
Volume	21
Issue number	17
Early online date	26 Aug 2019
DOIs	https://doi.org/10.1021/acs.orglett.9b02633
Publication status	Published - 6 Sept 2019

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.orglett.9b02633
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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.orglett.9b02633
Accepted author manuscript, 4.87 MB

Graeme Barker
- Graeme.Barkerhw.acuk
- School of Engineering & Physical Sciences - Assistant Professor
- School of Engineering & Physical Sciences, Institute of Chemical Sciences - Assistant Professor
Person: Academic (Research & Teaching)

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title = "Lithiation Substitution of Unprotected Benzyltetrazoles",

abstract = "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 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.",

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AU - Wong, Jeff Y. F.

AU - Lewandowska, Agnieszka

AU - Trowse, Benjamin

AU - Barker, Graeme

PY - 2019/9/6

Y1 - 2019/9/6

N2 - 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 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.

AB - 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 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.

U2 - 10.1021/acs.orglett.9b02633

DO - 10.1021/acs.orglett.9b02633

M3 - Article

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VL - 21

SP - 7069

EP - 7072

JO - Organic Letters

JF - Organic Letters

IS - 17

ER -

Lithiation Substitution of Unprotected Benzyltetrazoles

Abstract

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