Asymmetric Catalytic Synthesis Of Spirochroman Based On P-QMs Research On HDPEP Derivatives

Para-Quinone Methides(p-QMs)is a special dienone system that has constructed the core structure of many bioactive molecules and natural products through asymmetric catalysis,such as chiral spirochromic skeleton and chiral 2-(1-(4-hydroxyphenyl)ethyl)phenol(2-(1-(4-hydroxyphenyl)ethyl)phenol,HDPEP)analog structure.However,existing studies have found that most of the successfully constructed routes have deficiencies such as low chemical selectivity,low yield,and harsh reaction conditions.Therefore,there is an urgent need to construct new substrates and react with p-QMs to synthesize new spirochroman skeletons and chiral HDPEP structural compounds.In this paper,the oxa-Michael / 1,6-addition series reaction of p-QMs and isoxazolone was catalyzed by triethylamine for the first time.Through screening and optimizing the reaction conditions,the configuration of spiroisoxazolone color is controlled selectively.A series of 14 novel spiroisoxazolone chroman compounds were synthesized with high yield(up to 89% yield)and high diastereoselectivity(> 99: 1 dr).In this paper,the asymmetric 1,6-addition / hemiketalization / retro-Henry series reaction of p-QMs and ?-nitroketones catalyzed by chiral tertiary amine squaramide was achieved for the first time.The chiral HDPEP was selectively controlled by screening optimization of the reaction conditions.Of the configuration.A series of 22 chiral HDPEP new compounds were synthesized with high yield(up to 92% yield)and high enantioselectivity(up to> 99% ee).