Synthesis of Trifluoromethyl‐Substituted Tetrazoles via KI/TBHP‐Mediated Oxidative Annulation of Trifluoroacetimidohydrazides and Nitromethane

A metal‐free strategy for the preparation of trifluoromethyl‐substituted tetrazoles via KI/TBHP‐mediated oxidative annulation of readily available trifluoroacetimidohydrazides (TFAIHs) and nitromethane has been disclosed. In this transformation, CH 3 NO 2 is applied as both the inexpensive nitrogen synthon and reaction solvent, providing a straightforward access to a library of functionalized tetrazoles in moderate to good yields. Two plausible reaction pathways have been proposed on the basis of the preliminary mechanistic observations. The reaction could be scaled up to a 5 mmol scale and be applied to synthesize the key skeleton of GR205771, which is an orally active antiemetic NK 1 receptor antagonist.