Silver-mediated formal [4π + 2σ] cycloaddition reactions of bicyclobutanes with nitrile imines: access to 2,3-diazobicyclo[3.1.1]heptenes

Abstract

Despite recent advances in the synthesis of aza-bicyclo[3.1.1]heptanes (aza-BCHeps, which have an sp³-hybridized nitrogen atom) and azabicyclo[3.1.1]heptenes (aza-BCHepes, which have an sp²-hybridized nitrogen atom), which are bioisosteres of pyridine, construction of 2,3-diazobicyclo[3.1.1]heptenes (2,3-diazo-BCHepes), which have both sp²- and sp³-hybridized nitrogen atoms, has yet to be achieved. Herein, we disclose a method for silver-enabled formal [4π + 2σ] cycloaddition reactions between bicyclobutanes and nitrile imines (generated from hydrazonyl chlorides) to furnish a diverse array of 2,3-diazo-BCHepes, which feature both sp²- and sp³-hybridized nitrogen atoms embedded in a BCHepe framework. These compounds have the potential to serve as bioisosteres of both pyridines and pyridazines. Owing to the presence of the sp³-hybridized nitrogen, 2,3-diazo-BCHepes can be expected to exhibit geometries similar to those of aza-BCHepes and much better solubility. We demonstrated the synthetic utility of our method by carrying out a scaled-up reaction and diverse postcatalytic transformations.