Lithiation Substitution of Unprotected Benzyltetrazoles

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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)7069-7072
Number of pages4
JournalOrganic Letters
Volume21
Issue number17
Early online date26 Aug 2019
DOIs
Publication statusPublished - 6 Sep 2019

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Tetrazoles
Substitution reactions
Pharmaceutical Preparations

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Wong, Jeff Y. F. ; Lewandowska, Agnieszka ; Trowse, Benjamin ; Barker, Graeme. / Lithiation Substitution of Unprotected Benzyltetrazoles. In: Organic Letters. 2019 ; Vol. 21, No. 17. pp. 7069-7072.
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Lithiation Substitution of Unprotected Benzyltetrazoles. / Wong, Jeff Y. F.; Lewandowska, Agnieszka; Trowse, Benjamin; Barker, Graeme.

In: Organic Letters, Vol. 21, No. 17, 06.09.2019, p. 7069-7072.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lithiation Substitution of Unprotected Benzyltetrazoles

AU - Wong, Jeff Y. F.

AU - Lewandowska, Agnieszka

AU - Trowse, Benjamin

AU - Barker, Graeme

PY - 2019/9/6

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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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JO - Organic Letters

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SN - 1523-7060

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