Kinetic Resolution of Racemic 4-Substituted Chroman-2-ones Through Asymmetric Lactone Hydrogenation  

作　　者：Xiong Wu Hai-Tao Yue Xiao-Dong Zuo Xiao-Hui Yang Pu-Cha Yan Jian-Hua Xie Qi-Lin Zhou 

机构地区：[1]State Key Laboratory and Institute of Elemento-Organic Chemistry,College of Chemistry,Frontiers Science Center for New Organic Matter,Nankai University,Tianjin 300071 [2]Zhejiang Jiuzhou Pharmaceutical Co.,Ltd.,Taizhou,Zhejiang 318000

出　　处：《CCS Chemistry》2024年第10期2560-2576,共17页中国化学会会刊（英文）

基　　金：supported by the National Key R&D Program of China(grant no.2021YFA1500200);the National Natural Science Foundation of China(grant nos.92056105,92256303,22221002,and 22188101);the Fundamental Research Funds for the Central Universities,China,and the Haihe Laboratory of Sustainable Chemical Transformations,China.

摘　　要：Esters are abundant in natural and synthetic products and their conversion into primary alcohols holds great importance in fine chemical synthesis.However,achieving asymmetric hydrogenation(AH)of racemic esters with remote stereocenters via kinetic resolution(KR)remains a formidable challenge due to the difficulties associated with discerning spatially distant stereocenters.To address this issue,we have designed a hydroxy-assisted strategy that introduces a hydroxy group into racemicβ-aryl esters to facilitate hydrogenation and enhance chiral discrimination through a lactone form.By employing chiral Ir-SpiroPAP catalysts,we achieved exceptional AH of racemic 4-substituted chroman-2-ones,lactone form of ortho-hydroxylatedβ-aryl esters,via KR,resulting in impressive selectivity factor(s)values of up to 600.This approach exhibited significant efficacy for racemic chroman-2-ones containingβ-aryl,alkenyl,alkynyl,and alkyl groups,enabling the synthesis of chiralγ-aryl primary alcohols and the recovery of chiralβ-aryl esters or chroman-2-ones,typically difficult to access using existing methods.The scalability and broad synthetic applications of this method were exemplified by successfully synthesizing chiral drugs(R)-fesoterodine and enrasentan,alongside various chiral intermediates essential for producing chiral drugs and natural products.These promising results highlight the potential of this approach as a powerful tool for synthesizing valuable chiral compounds.

关 键 词：asymmetric hydrogenation chiralγ-aryl primary alcohols hydrogenation of esters iridium catalysts kinetic resolution 

分 类 号：O62[理学—有机化学]