Chiral Nucleophilic Catalysts: Applications in the Synthesis of3,3-Disubstituted Oxindoles and Parallel Kinetic Resolution.

[摘要] The enantioselective nucleophile-catalyzed rearrangements of oxindole-derived enol acetates and enol carbonates to quaternary carbon containing 3,3-disubstituted oxindoles have been developed.A strong dependence of the reaction rate on the oxindole protecting group was demonstrated.Using achiral DMAP, oxindole-derived enol acetates and enol carbonates protected with amides or sulfonamides rearrange to the 3,3-disubstitituted oxindoles within 20 min with low catalyst loading. In contrast, only partial conversion is observed for alkyl and carbamate protected oxindoles in 5 h.Taking advantage of this enhanced reactivity allowed for the highly enantioselective (>85% ee) rearrangement of enol acetates derived from amide protected oxindoles within a few hours with the readily available chiral amino alcohol-derived catalyst (AcOLeDMAP).The enol carbonates of amide protected oxindoles were also very reactive, but the chiral catalyst AcOLeDMAP decomposed over the course of the reaction.Replacement of the acetyl protecting group at oxygen on the catalyst by benzyl circumvented this problem, thereby allowing the development of highly enantioselective rearrangements of enol carbonates as well (>90% ee).The acetyl and carboxyl rearrangement reactions displayed complementary enantiofacial preference, so both enantiomers of the 3,3-disubstituted oxindoles can be obtained using a single enantiomer of the catalysts.A dual catalytic homogeneous parallel kinetic resolution (PKR) of racemic alcohols with achiral acyl donors and two chiral catalysts has been developed.A complementary anhydride selectivity of phosphine and DMAP catalysts was found.Using a mixture of aromatic and aliphatic anhydrides, phosphine catalysts selectively promoted the formation of aromatic esters while DMAP catalysts selectively promoted the formation of aliphatic esters.The use of two chiral catalysts, AcOLeDMAP and chiral phosphine P-aryl-2-phophabicyclo[3.3.0]octane (PhPBO), in parallel lead to the resolution of racemic alcohols to form two distinct enantioenriched esters (75% ee and 88% ee).

[发布机构] University of Michigan

[效力级别] Parallel Kinetic Resolution

[关键词] Asymmetric Nucleophilic Catalysis;Parallel Kinetic Resolution;Synthesis Quaternary Carbons;Chemistry;Science;Chemistry