摘要
以N-烷氧基邻苯二甲酰亚胺为底物,利用光与铜共催化,在蓝光照射下,实现了远程C—H键不对称氰基化反应.反应中涉及氧自由基的1,5-氢迁移过程,结合铜催化自由基接力的策略,以良好到优秀的对映选择性、单一的区域选择性得到了芳基取代的烷基醇类衍生物δ-位C—H键不对称氰基化产物.该方法条件温和,具有较好的官能团兼容性以及底物普适性,为光学活性的δ-氰基醇类化合物的合成提供了高效方法.
Optically pure alkylnitriles are important structural motifs found in agrochemicals,pharmaceuticals,and natural products,which can be further transferred to acids,amines and amides.Direct asymmetric cyanation of sp3 C—H bonds represents the most efficient synthetic pathway to these optically pure alkylnitriles.However,selective functionalization of sp3 C—H bonds remains a crucial issue due to the inertness of sp3 C—H bonds as well as the difficulties in the control of stereoand regioselectivity.Inspired by enzymatic oxygenases and halogenases,such as cytochrome P450 and nonheme iron enzymes,the radical-based C—H functionalization has received much attention,which was initiated with a hydrogen atom transfer(HAT)process.Recently,numerous reports have been disclosed for the highly efficient functionalization of C—H bonds with an intramolecular HAT process as a key step to govern the reactivity and site selectivity.Our group has developed a copper-catalyzed radical relay process for the enantioselective cyanation and arylation of benzylic C—H bonds using TMSCN and ArB(OH)2 as nucleophiles respectively.Mechanistic studies indicated that a benzylic radical generated via a radical replay process can be trapped by a reactive chiral copper(Ⅱ)cyanide enantioselectively,delivering optically pure benzyl nitriles efficiently.Herein,we communicate the catalytic asymmetric cyanation of remote C—H bonds by merging photoredox catalysis with copper catalysis.This reaction proceeds under mild reaction conditions and exhibits good functional group compatibility as well as wide substrates scope.Additionally,the nitrile group was further reduced to amide under hydrogen atmosphere.This reaction provides an efficient pathway to synthesize chiral δ-cyano alcohols and 1,6-amino alcohols.The general procedure is as following:in a dried sealed tube,substrate 1(0.2 mmol,1.0 equiv.),Cu(CH3CN)4PF6(0.01 mmol,5 mol%),L(0.015 mmol,7.5 mol%)and Ir(ppy)3(0.002 mmol,1 mol%)were dissolved in dichloromethane(4.0 mL)under N2 atmosphere
作者
成忠明
陈品红
刘国生
Cheng Zhongming;Chen Pinhong;Liu Guosheng(State Key Laboratory of Organometallic Chemistry,and Shanghai Hongkong Joint Laboratory in Chemical Synthesis,Center for Excellence in Molecular Synthesis,Shanghai Institute of Organic Chemistry,University of Chinese Academy of Sciences,Chinese Academy of Sciences,345 Lingling Road,Shanghai 200032)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2019年第9期856-860,共5页
Acta Chimica Sinica
基金
国家重点基础研究发展计划(973计划)(No.973-2015CB856600)
国家自然科学基金(Nos.21532009,21790330,21821002)
上海市科委(Nos.17XD1404500,17QA1405200,17JC1401200)
中国科学院前沿重点项目(No.QYZDJSSWSLH055)资助~~
关键词
不对称氰基化
C—H键
铜催化
光催化
1
5-氢迁移
enantioselective cyanation
C—H bonds
copper catalysis
photoredox catalysis
1
5-hydrogen atom transfer
