FEIST • BENARY Furan synthesis

Recent Advances in Furan Chemistry. Part I In Advances in Heterocyclic Chemistry, Katritzky, A. R., Ed. Academic Press New York, 1982 Vol. 30, 167-238. (Review). 

Friedrichsen, W. Furans and Their Benzo Derivatives Synthesis. In Comprehensive Heterocyclic Chemistry IT, Katritzky, A. R., Rees, C. W., Scriven, E. F. V. Bird, C. V. Eds. Pergamon New York, 1996 Vol. 2, 351-393. (Review). 

Product Class 9 Furans. In Science of Synthesis Houben—Weyl Methods of Molecular Transformations, Maas, G., Ed. Georg Thieme Verlag New York, 2001 Cat. 2, Vol. 9,183-278. (Review). 

Feist—Benary Furan Synthesis In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 160-167. (Review). 

Example 3, Ionic liquid-promoted intermpted Feist-Benary reaction 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 101, Springer International Publishing Switzerland 2014 

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

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 94, Springer-Verlag Berlin Heidelberg 2009 

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. 

An efficient synthetic sequence for the preparation of 2,4-b/s(trifluoromethyl)furan was developed by R. Filler and co-workers. The potassium enolate of ethyl 4,4,4-trifluoroacetate was reacted with 3-bromo-1,1,1-trifluoroacetate in DMSO to afford 2,4-bis (trifluormethyl)-4-hydroxydihydro-3-furoate as a result of O-alkylation. Interestingly, under these conditions usually C-alkylation is preferred. Next, dehydration was performed to give the corresponding 2,4-bis (trifluoromethyl)-3-furoate in good yield. Finally, decarboxylation by heating with quinoline and CUSO4 yielded the target furan in excellent yield. 

The mycotoxin patulin was synthesized via the oxidation of a disubstituted furan in the laboratory of M. Tada. The required 2,3-disubstituted furan was conveniently prepared via the Feist-Benary reaction of acetonedicarboxylic acid dimethyl ester and chloroacetaldehyde in the presence of pyridine. Subsequent functional group modification and oxidation of this furan finally gave the natural product. 

Research in the laboratory of H.M.I. Osborn showed that the use of cyclohexene derivatives as nucleophiles in the Lewis acid-mediated Type I carbon-Ferrier reaction of 3-0-acetylated glycals can be used to prepare unsaturated 3-linked C-disaccharides. The incorporation of the alkene took place with one equivalent of glucal in the presence of boron-trifluoride etherate in 33% yield. The desired C-disaccharide was obtained by selective hydrogenation of the exocyclic double bond in the presence of an endocyclic one. 

Williams and co-workers accomplished the first total synthesis of marine dolabellane diterpene (+)-4,5-deoxyneodolabelline. The Type I carbon-Ferrier reaction was utilized to assemble the key frans-2,6-disubstituted dihydropyran with complete stereoselectivity (a-anomer). The macrocyclization was carried out with a vanadium-based pinacoi coupiing. 

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The Feist-Benary furan synthesis occurs when an a-halocarbonyl (1) reacts with a P-dicarbonyl (2) in the presence of a base. The resulting product (3) is a 3-furoate that incorporates substituents present in the two starting materials. ... 

Chatteijea showed that cyclic ot-halocarbonyls are acceptable substrates for the Feist-Benary furan synthesis by combining 1-chlorocyclohexanone (34) with 1,3-cyclohexanedione (30) to yield octahydrodibenzofuran 35. ... 

Several modifications of the Feist-Benary furan synthesis have been reported and fall into two general classes 1) reactions that yield furan products 2) reactions that yield dihydrofuran products. One variant that furnishes dihydrofiirans uses substrates identical to the traditional Feist-Benary furan synthesis with a slight modification of the reaction conditions. The other transformations covered in this section involve the combination of P-dicarbonyls with reagents that are not simple a-halocarbonyls. Several reactions incorporate a-halocarbonyl derivatives while others rely on completely different compounds. 

The final variation of the Feist-Benary furan synthesis encompasses reactions of 1,3-dicarbonyls with 1,2-dibromoethyl acetate (52). For example, treatment of ethyl acetoacetate (9) with sodium hydride followed by addition of 52 at 50°C yields dihydrofuran 53. The product can be easily converted into the corresponding 2-methyl-3-furoate upon acid catalyzed elimination of the acetate, thus providing another strategy for the synthesis of 2,3-disubstituted furans. 

The method described has some features in common with the well-known, but apparently little-used, Feist-Benary furan synthesis,1 which uses an a-haloketone in place of the sulfonium salt. Acetylenic bromides suitable for preparing the sulfonium salts are readily available by well-documented procedures involving acetylenic organometallic compounds. 

The synthesis of furans from /3-ketoesters and a-halogenated aldehydes or ketones under basic conditions is known as the Feist-Benary furan synthesis (Equation 28). In most of the cases, the reaction is initiated by an aldol reaction. If the first step is alkylation, reversed regioselectivity is observed. 

P-keto ester substituted furan Feist-Benary furan synthesis... 

Z3.3. The Feist-Benary Furan Synthesis. In this synthesis, an aldol-type carbonyl-carbanion condensation and a halogen displacement by an enol are employed to bring two molecules together in a ring stmc-ture, and in this sense it resembles the Knorr synthesis. The reactants are an alpha-haloketone and a ketoester (like ethyl acetoacetate). The mechanistic details remain unclear, but a logical mechanism is shown in Scheme 4.34. This assumes the carbonyl condensation occurs first before the halogen displacement, but the reverse may be tme. 

The Feist-Benary furan synthesis, first described in 1902, is especially useful for the synthesis of substituted furan rings. This reaction occurs... 

The Feist-Benary furan synthesis is most commonly used for the preparation of 2-substituted 3-furoates, including ethyl 2-methyl-3-furoate, the original compound prepared by Benary. The resulting ester is generally converted into a carboxylic acid for use in a variety of transformations, including decarboxylation to produce the corresponding 2-substituted furan. For example, reaction of ethyl 7-methyl-3-oxooct-6-enoate with... 

Feist-Benary Furan Synthesis, Feist-Benary Condensation)... 

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