A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ...A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald-Hartwig amidation of carboxylic amide and aryl chloride. A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549, human liver cancer cell BEL7402, and human colon cancer cell HCT-8. The results show that most of the library compounds 2 have some inhibitory activities. 2-（Trifluoromethoxy） benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549 （IC50 = 50 nmol/L）.展开更多
A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an eff...A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an efficient method for synthesizing various aryl-substituted spirocyclic oxindoles.The protocol enables three C-C bonds formation via an intramolecular Heck reaction and sequentially regioselective C-H bond activation.展开更多
The enantioselective double Michael reaction of N-Boc-3-nonsubstitued oxindoles with dienones catalyzed by chiral monoimide protected cyclohexane-1,2-diamines was developed. A wide range of optically active spirocycli...The enantioselective double Michael reaction of N-Boc-3-nonsubstitued oxindoles with dienones catalyzed by chiral monoimide protected cyclohexane-1,2-diamines was developed. A wide range of optically active spirocyclic oxindoles were obtained up to 98% yield and up to 89% ee.展开更多
Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less esta...Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less established.In this note,the NHC-catalyzed all carbon[4+2]cyclocondensation of α,β-unsaturated acyl chlorides and 3-alkenyloxindoles was developed to give the corresponding spirocarbocyclic oxindoles in good yield with good to high diastereoselectivities.展开更多
The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobut...The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobutyl amides with C(sp^(3))−H feedstocks is achieved in an atom-economic and photocatalyst-and light-free manner.This protocol follows a sequential C(sp^(3))–H/C(sp^(2))–H functionalization,providing an efficient route for diversity-oriented synthesis of functionalized 3-spirocyclobutyl oxindoles.In particular,a wide range of C(sp^(3))−H feedstocks,including ether,alcohol,amine,thioether,polychlorinated methane,silane,acetone,acetonitrile,toluene,and alkane are all suitable for the C(sp^(3))−H functionalization,demonstrating the broad applicability of this transformation.展开更多
基金supported by the program of research fund for returning scholars of Ministry of Education of China(No.200812)the Open Foundation of Chemical Engineering Subject(No.200903),Qingdao University of Science & Technology,China
文摘A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald-Hartwig amidation of carboxylic amide and aryl chloride. A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549, human liver cancer cell BEL7402, and human colon cancer cell HCT-8. The results show that most of the library compounds 2 have some inhibitory activities. 2-（Trifluoromethoxy） benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549 （IC50 = 50 nmol/L）.
基金the National Natural Science Foundation of China (Nos.21572051,21602057,21901071,and 21971061)Natural Science Foundation of Hunan Province (Nos.2020JJ5350 and 2020JJ5347)+1 种基金Scientific Research Fund of Hunan ProvincialEducation Department (Nos.18A002,19B359 and 17C1137)Science and Technology Planning Project of Hunan Province (No. 2018TP1017) for financial support。
文摘A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an efficient method for synthesizing various aryl-substituted spirocyclic oxindoles.The protocol enables three C-C bonds formation via an intramolecular Heck reaction and sequentially regioselective C-H bond activation.
文摘The enantioselective double Michael reaction of N-Boc-3-nonsubstitued oxindoles with dienones catalyzed by chiral monoimide protected cyclohexane-1,2-diamines was developed. A wide range of optically active spirocyclic oxindoles were obtained up to 98% yield and up to 89% ee.
基金Financial support from National Natural Science Foundation of China(No.21272237)the Ministry of Science and Technology of China(No.2011CB808600)the Chinese Academy of Sciences is gratefully acknowledged.
文摘Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less established.In this note,the NHC-catalyzed all carbon[4+2]cyclocondensation of α,β-unsaturated acyl chlorides and 3-alkenyloxindoles was developed to give the corresponding spirocarbocyclic oxindoles in good yield with good to high diastereoselectivities.
基金funded by National Natural Science Foundation of China(No.22201070).
文摘The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobutyl amides with C(sp^(3))−H feedstocks is achieved in an atom-economic and photocatalyst-and light-free manner.This protocol follows a sequential C(sp^(3))–H/C(sp^(2))–H functionalization,providing an efficient route for diversity-oriented synthesis of functionalized 3-spirocyclobutyl oxindoles.In particular,a wide range of C(sp^(3))−H feedstocks,including ether,alcohol,amine,thioether,polychlorinated methane,silane,acetone,acetonitrile,toluene,and alkane are all suitable for the C(sp^(3))−H functionalization,demonstrating the broad applicability of this transformation.
