Cinchona Alkaloid/Ti^IV‐Catalyzed Enantioselective Enamine–Trifluoropyruvate Condensation–Cyclization Reaction and Its Application to Drug‐like Heterocycles

Abstract

Hidden benefits: The enantioselective organocatalytic protonation of silyl enolates has been achieved by using readily available cinchona alkaloid catalysts (1) and a latent source of HF that delivers “at will” the active catalytic hydrogen fluoride salt (1‐HF). This approach leads to enantioselective proton transfer with high enantioselectivities of up to 92 % under mild, neutral, and metal‐free conditions (see scheme, TMS=trimethylsilyl).

Exploring the regioselectivity of the cyanoalkylation of 3-aza-1,5-dienes: photoinduced synthesis of 3-cyanoalkyl-4-pyrrolin-2-ones

“…1). 3 Nevertheless, methodologies for the construction of such a privileged structural motif are somewhat scarce, and a transition-metal catalyst 4–6 and/or harsh reaction conditions are generally required. 5–8 Therefore, the development of new protocols to access functionalized 4-pyrrolin-2-ones in a mild and sustainable manner is still challenging and highly desirable.…”

Construction of poly-N-heterocyclic scaffolds via the controlled reactivity of Cu-allenylidene intermediates

“…2c). During our research into the development of efficient synthetic methods for the synthesis of fluorine-containing heterocyclic compounds for drug discovery [46][47][48][49][50][51][52][53][54][55][56][57] , we noticed that the use of a CF 3 substituent as the X group can direct the reaction pathway from mode A to B 55 . Herein, we realize the idea of a cascade of inter-and intramolecular annulations (mode B), which involves both αand β-attacks by employing 4-ethynyl-4-CF 3benzoxazinanones 1 (X = CF 3 ) and cyclic sulfamate-imines 2 (Fig.…”

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

“…In some cases, the target heterocycles with both enantiomers were generated by just tuning the configuration of the cinchona alkaloid (Scheme 37). [101] These studies provide attractive approaches for the development of new drugs with fused lactam heterocycles.…”