NHC-catalysed[3+2]-asymmetric annulation between pyrazolin-4,5-diones and enals:synthesis of novel spirocyclic pyrazolone γ-butyrolactones and computational study of mechanism and stereoselectivity

作     者：Marta Gil-Ordonez Alicia Maestro Pablo Ortega Pablo G.Jambrina Jose M.Andres 

作者机构：GIR-SintACat-Instituto Universitario CINQUIMA y Departamento de Química OrgánicaFacultad de CienciasUniversidad de ValladolidPaseo Belén 747011 ValladolidSpain Departamento de Química FísicaUniversity of Salamanca37008 SalamancaSpain 

出 版 物：《Organic Chemistry Frontiers》 (有机化学前沿（英文）)

年 卷 期：2022年第9卷第2期

页      面：420-427页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：Junta de Castilla y León(Projects:FEDER-VA115P17,and VA149G18)for financial support the Laboratory of Instrumental Techniques(LTI)Research Facilities,Universidad de Valladolid Junta de Castilla y León for a predoctoral fellowship(EDU/556/2019) grant PID2020-113147GA-I00 funded by MCIN/AEI/10.13039 by the Fundación Salamanca City of Culture and Knowledge(programme for attracting scientific talent to Salamanca) Grant No.EDU/601/2020(Junta de Castilla y Leon and European Social Fund) 

主　　题：synthesis spiro mechanism 

摘      要：Chiral pyrazolones with a spirocyclic centre at the C4-position are widely found in a large family of medically relevant *** recent years,organocatalysis,particularly that performed with quiral N-heterocyclic carbenes(NHCs),has allowed the enantioselective synthesis of these spirocyclic compounds despite its inherent *** this work,we describe the fully diastereo-and highly enantioselective synthesis of novel spirocyclic pyrazolone γ-butyrolactones via NHC-catalysed[3+2]annulation reaction of enals and 1H-pyrazol-4,*** understand the catalytic mechanism and origin of stereoselectivity,electronic structure calculations were carried *** considering various pathways,we concluded that the stereoselectivity-determining step is the formation of the lactone that proceeds after addition of the NHC derived homoenolate to the electrophilic carbonyl group of pyrazolin-4,*** calculations predict that the free energy barrier is lower for the(RS)product,which is also the main product experimentally obtained.