Bicyclic [n.1.1]alkane derivatives, their preparation methods and applications

Abstract

This invention belongs to the field of pharmaceutical intermediates, specifically relating to bicyclic [n.1.1]alkane derivatives, their preparation methods, and applications. This invention is based on a diversity-oriented synthetic method using alkenyl diazo compounds and bicyclic [1.1.0]butane compounds. This method, under Lewis acid catalysis, in the presence of an organic solvent and a 4Å molecular sieve, yields a bicyclic [2.1.1]hexane derivative in a one-step reaction. After this step, a transition metal catalyst is added to continue the reaction, yielding a 2-alkylene bicyclic [2.1.1]hexane derivative; or, by changing the solvent and temperature conditions, a one-pot reaction is used to obtain a bicyclic [3.1.1]hept-2-ene derivative. The method of this invention has advantages such as economical steps, mild conditions, simple operation, wide substrate adaptability, and high yield. The three synthesized derivatives all exhibit significant anti-cervical cancer and clear cell renal cell carcinoma activities, making them important pharmaceutical and chemical intermediates.

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