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Dehydrative fragmentation of 5-hydroxyalkyl-1H-tetrazoles: a mild route to alkylidenecarbenes.

ABSTRACT: The development of a mild, base-free method for the generation of alkylidenecarbenes is reported. Treatment of 5-hydroxyalkyl-1H-tetrazoles with carbodiimides generates products arising from the 1,2-rearrangement or [1,5]-C-H bond insertion of a putative alkylidenecarbene. Formation of this divalent intermediate is proposed to occur by way of a tetraazafulvene, which undergoes extrusion of 2 mol of dinitrogen. Details of this methodology, its application to the synthesis of combretastatin A-4, and an improved route to 5-hydroxyalkyl-1H-tetrazoles are described.

SUBMITTER: Wardrop DJ

PROVIDER: S-EPMC3306463 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Dehydrative fragmentation of 5-hydroxyalkyl-1H-tetrazoles: a mild route to alkylidenecarbenes.

Wardrop Duncan J DJ Komenda John P JP

Organic letters 20120228 6

The development of a mild, base-free method for the generation of alkylidenecarbenes is reported. Treatment of 5-hydroxyalkyl-1H-tetrazoles with carbodiimides generates products arising from the 1,2-rearrangement or [1,5]-C-H bond insertion of a putative alkylidenecarbene. Formation of this divalent intermediate is proposed to occur by way of a tetraazafulvene, which undergoes extrusion of 2 mol of dinitrogen. Details of this methodology, its application to the synthesis of combretastatin A-4, a ...[more]

PMID: 22372676

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