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 

机构地区：[1]GIR-SintACat-Instituto Universitario CINQUIMA y Departamento de Química Orgánica,Facultad de Ciencias,Universidad de Valladolid,Paseo Belén 7,47011 Valladolid,Spain [2]Departamento de Química Física,University of Salamanca,37008 Salamanca,Spain

出　　处：《Organic Chemistry Frontiers》2022年第2期420-427,共8页有机化学前沿（英文）

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).

摘　　要：Chiral pyrazolones with a spirocyclic centre at the C4-position are widely found in a large family of medically relevant compounds.In recent years,organocatalysis,particularly that performed with quiral N-heterocyclic carbenes(NHCs),has allowed the enantioselective synthesis of these spirocyclic compounds despite its inherent difficulty.In 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-4,5-diones.To understand the catalytic mechanism and origin of stereoselectivity,electronic structure calculations were carried out.After 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-4,5-dione.Our calculations predict that the free energy barrier is lower for the(RS)product,which is also the main product experimentally obtained.

关 键 词：synthesis spiro mechanism 

分 类 号：O62[理学—有机化学]