Catalytic, Asymmetric, “Interrupted” Feist−Bénary Reactions

Abstract

Pyrimidine derivatives of the cinchona alkaloids function as excellent asymmetric catalysts for the "Interrupted" Feist-Bénary Reaction. This reaction produces highly substituted hydroxydihydrofurans from simple starting materials under mild conditions. The asymmetric reaction gives high enantioselectivities with unsubstituted bromoketones, and high enantio- and diastereoselectivities with substituted substrates. Mechanistic experiments suggest that the hydrobromide salt of the alkaloid derivative is the active catalyst for the reaction.

Investigation on 1,4‐dichlorophthalazine‐derivatized cinchona alkaloids‐catalyzed asymmetric “interrupted” Feist–Bénary reaction

“…5 (DHQD) 2 PHAL 1d and (DHQ) 2 PHAL 1c were the optimal catalysts in the reaction of ethyl bromopyruvate and the phenyl-substituted bromoketoester, respectively. Further investigations are planned to provide additional information with regard to the scope and precise mechanism of the reaction.…”

“…3,4 Calter et al first reported the application of cinchona alkaloid catalysts in IFB reactions. 5 They coupled different substituted pyrimidinyls with cinchona alkaloids to afford a series of catalysts and found that diphenylpyrimidinyl derivatives gave optimal asymmetric induction. Interestingly, slight changes to a substituent of the catalysts or different cinchona alkaloids significantly affected the enantiomeric purity of products (14-98%).…”

Basic ionic liquids. A short review

“…The IFB reaction is important for an easy access to substituted dihydrofurans which are constituents of many natural products arising from plants and marine organisms with promising biological activities. However, only a limited number of methods are available for FB and IFB reactions [114][115]. The basic ionic liquid, 1-butyl-3-methylimidazolium hydroxide promoted the interrupted Feist-Benary reaction at room temperature under organic solvent-free conditions to produce a variety of substituted hydroxydihydrofurans.…”

Cinchona‐Catalyzed Cycloaddition Reactions

“…They proposed that the protonated cinchona alkaloid would perform as a Brønsted acid to form hydrogen-bonding interaction with a-ketoester moiety, rendering it more electrophilic toward attack by either the enol or enolate of cyclohexandione. Then intramolecular alkylation would afford the formal [3 þ 2] cycloadduct (Scheme 10.12) [16].…”

“…A variety of azomethine imines reacted directly with cyclic enones, forming the desired tricyclic products in good yield (72-99%) and ee (86-95%), while having excellent diastereoselectivity (all >99 : 1) (Table 10.9). Moreover, 6 0 -OH-9-amino-9-deoxyepi-quinidine 1r from quinidine was also prepared, and good results were gained while the products had the opposite configuration (entries [16][17][18][19]. Hence, both enantiomers of the cycloaddition products could be readily attainable.…”