摘要
We report an unprecedented Pd-catalyzed asymmetric allylic alkylation of 1-(indol-2-yl)cyclobutanols followed by anα-iminol rearrangement.High yields with excellent chemo-,regio-,diastereo-,and enantioselectivities have been realized,affording a wide range of enantioenriched 2-spirocyclicindolines bearing two contiguous stereocenters.The facial selectivity of the ensuing rearrangement is controlled by the subtle difference of the substituents on the all-carbon quaternary stereogenic center formed in the allylic alkylation step.Nonactivated racemic terminal allylic alcohols are utilized as efficient electrophiles via kinetic resolution pathways for the first time in Pd-catalyzed asymmetric allylic alkylation.The role of Et3B additive is pivotal to activating allylic alcohols toward the formation of π-allylpalladium species and suppressing N/O allylic alkylation of indole with enhanced C3-nucleophilicity.Electrospray ionization high-resolution mass spectrometry(ESIHRMS)experiments provided strong evidence for the existence of the key nucleophilic boron anionic species,which fully accounts for the essential role of the Et_(3)B additive.The study of the mechanism indicates that the real catalytically active species is an electronic π-cinnamyl-palladium complex coordinated by two phosphoramidite ligands,which is consistent with the observed nonlinear effect and control experiments and is further confirmed by X-ray structure analysis.
基金
supported by the NSFC(nos.21525207,21772147,and 220711186)
the Huibei Province Natural Science Foundation(no.2020CFA036)
Support by the Fundamental Research Funds for the Central Universities
the Program of Introducing Talents of Discipline to Universities of China(111 Program)is also appreciated.
