Cinchona Urea-Catalyzed Asymmetric Sulfa-Michael Reactions: The Brønsted Acid−Hydrogen Bonding Model

Abstract

The cinchona alkaloid-derived urea-catalyzed asymmetric conjugate addition of aromatic thiols to cycloalkenones was studied using density functional theory (DFT). Deprotonation of the thiol gives a protonated amine that activates the electrophile by Brønsted acid catalysis, while the urea group binds the nucleophilic thiolate by hydrogen bonding. These results demonstrate the generality of the Brønsted acid-hydrogen bonding transition state (TS) model for cinchona alkaloid catalysis that we recently showed to be favored over Wynberg's widely accepted ion pair-hydrogen bonding model and represent the first detailed mechanistic study of a cinchona urea-catalyzed reaction. The conformation of the catalyst methoxy group has a strong effect on the TS, an effect overlooked in previous mechanistic studies of reactions catalyzed by cinchona alkaloids.

Enantioselective Synthesis of 2,3‐Dihydrofurocoumarins by Squaramide‐Catalyzed Michael Addition/Cyclization of 4‐Hydroxycoumarins with β‐Nitrostyrenes

“…Based on configuration determination, we devised a transition state model, which explains the formation of products ( S )‐ 3 using catalyst ( S,R,R )‐ C9 (Figure ). The transition state model takes into consideration the calculations by Papai, and more recently by Houk, Wong, as well as Goldfuss . Contrary to the Takemoto model, this model suggests that the electrophile is bound by the protonated tertiary amine and the nucleophile by squaramide moiety.…”

Asymmetric Synthesis of 3‐Amino Oxindoles Using Isatin‐Derived N‐Boc Ketimines with Activated Nitroolefin Catalyzed by Organocatalysts

“…Activated nitrolefin having 4‐chloro substituent ( 3 ) as necleophile when reacted with 5‐Br ( 1 j ) and 5‐Me ( 1 k ) substituted N ‐Boc ketimines resulted into the products 1′j–k with high diastereoselectivty (dr: 99:1 & 99:1), good enantioselectivity (er: 91:9 & 86:14) and moderat yields (76 & 78 %, entries, 10 &11). The cooperative binding arising from noncovalent week interaction between catalyst and substrates is instrumental which is governing stereoinduction in chiral H‐bond catalyzed asymmetric reactions . We have interpretated the role of catalyst OC‐7 in asymmetric aza‐MBH reaction of 1‐methylisatin derived N ‐Boc ketimine as representative substrate with activated nitroolefin nucleophile, we have conducted a series of 1 H‐NMR experiments in CDCl 3 .…”

Direct Noncovalent Activation of α,β‐Unsaturated Aldehydes for the Stereodivergent Synthesis of Substituted Cyclohexenes

“…On the basis of X-ray crystallographic analysis, control experiments, and previous reports, [16] the workingm ode of this reaction was proposed ( Figure 1). On the basis of X-ray crystallographic analysis, control experiments, and previous reports, [16] the workingm ode of this reaction was proposed ( Figure 1).…”