Generation of Alkylidene Carbenes through Tetrazole Fragmentation: Recent Advances and Applications in Organic Synthesis

Abstract Tetrazole fragmentation under mild conditions from 5-hydroxyalkyl-1H-tetrazoles (HATs) or cyanophosphates (CPs) readily generates the corresponding alkylidene carbenes, which undergo [1,2]-rearrangements or [1,5]-C–H insertions to yield one-carbon homologous alkynes or five-membered unsaturated carbocycles, respectively. Furthermore, azido-HATs and 2-cyanoazetidines afford propargylic and homopropargylic amines, respectively, via [1,2]-rearrangement of the corresponding aminoalkyl alkylidene carbenes. These reactions are successfully applied for the synthesis of various biofunctional molecules. This short review summarizes the progress made on this methodology over the last decade. 1 Introduction 2 Early Studies 3 Tetrazole Fragmentation of HATs, Azido-HATs, and 2-Cyanoazetidines 4 HAT Synthetic Methods 5 Tetrazole Fragmentation from CPs 6 Summary and Perspective