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Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition.

ABSTRACT: Propargylamines are popular substrates for triazole formation, but tetrasubstituted variants have required multistep syntheses involving stoichiometric amounts of metal. A recent cyclohexanone-amine-silylacetylene coupling forms silyl-protected tetrasubstituted propargylamines in a single copper-catalyzed step. The development of the tandem silyl deprotection-triazole formation reported herein offers rapid access to alpha-tetrasubstituted triazoles. A streamlined two-step approach to this uncommon class of hindered triazoles will accelerate exploration of their therapeutic potential. The superior activity of copper(II) triflate in the formation of triazoles from sensitive alkyne substrates extends to simple terminal alkynes.

SUBMITTER: Palchak ZL

PROVIDER: S-EPMC4578341 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition.

Palchak Zachary L ZL Nguyen Paula T PT Larsen Catharine H CH

Beilstein journal of organic chemistry 20150814

Propargylamines are popular substrates for triazole formation, but tetrasubstituted variants have required multistep syntheses involving stoichiometric amounts of metal. A recent cyclohexanone-amine-silylacetylene coupling forms silyl-protected tetrasubstituted propargylamines in a single copper-catalyzed step. The development of the tandem silyl deprotection-triazole formation reported herein offers rapid access to alpha-tetrasubstituted triazoles. A streamlined two-step approach to this uncomm ...[more]

PMID: 26425198

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