Enantioselective Construction of Spirooxindole-Fused Cyclopentanes
The present study reports an asymmetric organocatalytic cascade reaction of oxindole derivates with α,β-unsaturated aldehydes efficiently catalyzed by simple chiral secondary amine. Spirooxindole-fused cyclopentanes were produced in excellent isolated yields (up to 98%) with excellent enantiopurities (up to 99% ee) and moderate to high diastereoselectivities. The synthetic utility of the protocol was exemplified on a set of additional transformations of the corresponding spiro compounds. In addition, a study showing the promising biological activity of selected enantioenriched products was accomplished.
Do?ekal, Vojtěch,Vopálenská, Andrea,Měrka, Pavel,Kone?ná, Klára,Jand'Ourek, Ond?ej,Pour, Milan,Císa?ová, Ivana,Vesely, Jan
p. 12623 - 12643
(2021/07/31)
Enantioselective Synthesis of N-Alkylamines through β-Amino C-H Functionalization Promoted by Cooperative Actions of B(C6F5)3and a Chiral Lewis Acid Co-Catalyst
We disclose a catalytic method for β-C(sp3)-H functionalization of N-alkylamines for the synthesis of enantiomerically enriched β-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C6F5)3, and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of N-alkylamines and α,β-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a N-alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is highlighted by late-stage β-C-H functionalization of bioactive amines. Investigations in regard to the mechanistic nuances of the catalytic processes are described.