Enantioselective Alkylative Kinetic Resolution of 2-Oxindole-Derived Enolates Promoted by Bifunctional Phase Transfer Catalysts

Abstract

The first strategy for bringing about highly enantioselective alkylative enolate kinetic resolutions using a simple phase-transfer protocol via S2 chemistry has been developed. In the presence of a new squaramide-based quaternized cinchona alkaloid-derived catalyst and aqueous base, benzyl, allyl, and propargyl halides react with racemic substituted oxindoles to generate densely functionalized products with the two contiguous stereocenters, one of which is an all-carbon quaternary.

Assisted by Hydrogen-Bond Donors: Cinchona Quaternary Salts as Privileged Chiral Catalysts for Phase-Transfer Reactions

“…In this way, 12 compounds containing a quaternary stereogenic center were achieved with high yields and enantiomeric excesses of up to 97%. Connon 35 also demonstrated this methodology for the concise synthesis of (-)-debromoflustramine B using a product of the developed enantioselective alkylation reaction as the starting material (Scheme 13). The described method is distinguished using a simple S N 2-based approach.…”

“…Cinchona alkaloids catalyzing reactions through carbanion conversions. One such example employs a catalyst bearing a squaric acid amide motif applied by the Connon group, 35 which was previously developed and utilized in the -fluorination of -keto esters by the Duan 38 group (Scheme 15).…”

Chiral Phase-Transfer Catalysts with Hydrogen Bond: A Powerful Tool in the Asymmetric Synthesis

“…Connon and co-workers also reported the new quaternary ammonium salts with square amide for the kinetic resolution of 2-oxindole-derived enolates (Scheme 7) [23]. Under the optimized conditions, the benzylated, allylated, and propargylated 2-oxindole units can be effectively furnished with high yield and excellent enantioslectivities.…”

“…Under the optimized conditions, the methylated catalyst and the tertiary amine catalyst were not suitable for the asymmetric nitro-Mannich reaction, and low enantioselectivity and yield were obtained. Connon and co-workers also reported the new quaternary ammonium salts with square amide for the kinetic resolution of 2-oxindole-derived enolates (Scheme 7) [23]. Under the optimized conditions, the benzylated, allylated, and propargylated 2-oxindole units can be effectively furnished with high yield and excellent enantioslectivities.…”

Base-free enantioselective SN2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

“…In this context, we realised that phase-transfer catalysis, due to its operational simplicity and utility in mediating reactions involving charged intermediates, could be an excellent methodology for the enantioselective S N 2 alkylation of enolates derived from the 2-oxindole core [13][14][15][16][17][18][19][20][21][22][23]. In recent years, several examples regarding the alkylation of 3-subsituted-2-oxindoles, via asymmetric phase-transfer catalysis, have been reported [24][25][26][27][28][29][30].…”