Dehydrative Fragmentation of 5-Hydroxyalkyl-1<i>H</i>-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-1<i>H</i>-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-1<i>H</i>-tetrazoles are described