Interrupted Feist-Benary

Three other modifications of the standard conditions provide synthetically useful strategies for the preparation of dihydrofurans. One method, called the interrupted Feist-Benary reaction, utilizes milder reaction conditions to stop the final dehydration step. For example, Calter combined bromide 47 with dicarbonyl 48 to produce dihydrofuran 49 as a mixture of diastereomers. He examined the scope and diastereoselectivity of this process and applied this reaction toward the synthesis of the polycyclic core of the zaragozic acids. A method principally designed to yield practical syntheses of cyclic ketodiesters also furnished a dihydrofuran via a variation of the interrupted Feist-Benary reaction. ... 

An efficient synthesis of the 7-deoxy zaragozic acid core was deveioped by M.A. Calter and co-workers. The assembly of this complex structure was based on the interrupted Feist-Benary reaction, which produces highiy oxygenated dihydrofuranols that can be isolated. To this end, the sodium enolate of malondialdehyde was reacted with 2-bromo-3-oxo-diethyl succinate in benzene at room temperature to afford 29% of the c/s-dihydrofuranol. This product was converted to the zaragozic acid core in four steps. 

Apart from acting as effective Lewis base catalysts, the quinuclidine structure of cinchona alkaloids can also participate in the other cycloaddition reaction by a different catalytic mechanism. Calter et al. described an interesting asymmetric interrupted Feist-Benary reaction between ethyl bromopyruvates and cyclohexadione. They proposed that the protonated cinchona alkaloid would perform as a Bronsted acid to form hydrogen-bonding interaction with a-ketoester moiety, rendering it more electrophilic toward attack by either the enol or enolate of cydohexandione. Then intramolecular alkylation would afford the formal [3 + 2] cycloadduct (Scheme 10.12) [16]. 

Scheme 10.12 Catalytic mechanism for the asymmetric interrupted Feist-Benary reaction.

The condensation reaction of (3-dicarbonyl compounds with a-haloketones to generate hydroxydihydrofuran is known as an interrupted Feist-Benary reaction. Calter et al. reported an enantioselective version of this reaction [26]. The aldol reaction of diketone with a-bromo-a-ketoester followed by cyclization proceeded in the presence of dimeric cinchona alkaloid catalyst to give cyclized product in high yield with high ee... 

Calter, M.A., Phillips, R.M. and Flaschenriem, C. (2005) Catal3ftic, asymmetric, interrupted Feist-Benary reactions. Journal of the American Chemical Society, 127, 14566-14567. 

Example 3, Ionic liquid-promoted interrupted Feist-Benary reaction ... 

Example 4, interrupted Feist-Benary reaction of a-tosyloxy-acetophenones... 

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