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Asymmetric [3+2] Annulations to Construct 1,2‐Bispirooxindoles Incorporating a Dihydropyrrolidine Motif
Author(s) -
He Qing,
Du Wei,
Chen YingChun
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700849
Subject(s) - chemistry , isatin , annulation , regioselectivity , enantioselective synthesis , organocatalysis , catalysis , stereoselectivity , combinatorial chemistry , stereochemistry , trifluoromethyl , structural motif , organic chemistry , alkyl , biochemistry
Constructing chiral bispirooxindoles is difficult to achieve but highly attractive owing to their many potential applications in medicinal chemistry. Here we present an asymmetric [3+2] annulation reaction of Morita–Baylis–Hillman carbonates from isatins and isatin‐based N ‐Boc‐ketimines under the catalysis of a newly designed multifunctional 4‐dimethylaminopyridine‐type substance. The reaction shows high γ‐regioselectivity, producing highly complex 1,2‐bispirooxindoles incorporating a dihydropyrrolidine motif in excellent yields with moderate to outstanding stereoselectivity ( dr >19:1, up to >99% ee ). This protocol has been expanded to utilize trifluoromethyl‐containing ketimines, delivering complicated architectures with fused and spirocyclic frameworks in modest enantioselectivity.