Pummerer-type reactions

A very interesting approach to optically active sulphoxides, based on a kinetic resolution in a Pummerer-type reaction with optically active a-phenylbutyric acid chloride 269 in the presence of /V,A -dimethyIaniline, was reported by Juge and Kagan332 (equation 149). In contrast to the asymmetric reductions discussed above, this procedure afforded the recovered sulphoxides in optical yields up to 70%. Chiral a, /1-unsaturated sulphoxides 270 were prepared via a kinetic resolution elaborated by Marchese and coworkers333. They found that elimination of HX from racemic /i-halogenosulphoxides 271 in the presence of chiral tertiary amines takes place in an asymmetric way leading to both sulphoxides 270 and 271, which are optically active (optical yields up to 20%) with opposite configurations at sulphur (equation 150). 

Chlorodiphenylphosphine 488 reacts with a-sulphinyl carbanions to give a-sulphinylphosphines 489 which undergo ready isomerization to a-sulphenylphosphine oxides 4W (equation 295). The report of Almog and Weissman that a-sulphinyl carbanions react with phosphorochloridates 491 to give a-phosphoryl sulphoxides 492 calls for correction (equation 296). Actually, the phosphorylation occurs at the oxygen atom of the ambident dimsyl anion, and is followed by the Pummerer-type reaction affording diethylphosphoric acid and tetraethyl pyrophosphate among other products . ... 

A combination of 2,3 sigmatropic rearrangement (Pummerer-type reaction) followed by an electrophilic aromatic substitution of the intermediate sulfenium ion, the formation of an iminium ion and, finally, a second electrophilic aromatic substitution, was used by Daich and coworkers for the synthesis of iso-indolo-isoquinolinones as 4-314 (Scheme 4.68) [106]. Thus, reaction of the two diastereo-meric sulfoxides 4-313, easily obtainable from 4-312 by a Grignard reaction and oxidation, led to 4-314 as a single product after crystallization in 42% yield. 

The synthesis of 4,5-diaryl-6-phenylsulfanyl-2,3-benzo-l,3a,6a-triazapentalenes 239 through Pummerer-type reactions of (benzotriazol-l-yl)allylic sulfoxides 238 with trifluoroacetic anhydride in THF has been reported (Equation 35) <2002EJ0493>. Similarly, unstable solid imines 240 treated without purification with trifluoroacetic anhydride (TFAA) provide 241 (Equation 36) <2003TL7507>. 

Recently, Juge and Kagan (68) reported that a more efficient kinetic resolution of racemic sulfoxides takes place in the Pummerer-type reaction with optically active a-phenylbutyric acid chloride 38 in the presence of N,A-dimethylaniline. In contrast to the asym-... 

Ene reactions of Pummerer-type reaction intermediates have been used as key steps in the synthesis of both pellitorine and trichonine. ... 

The action of phosphorus halides on pyrrolinones and related compounds offers an alternative route to chloropyrroles. Yields of around 60% of 2,5-dichloropyrroles were obtained in this way from N-substituted succinimides (82ZC126). Vilsmeier reaction of N-alkylsuccinimidals formed chlorinated pyrrole aldehydes in modest yields (90CJC791), and there are other examples [66YZ158 81H(15)547]. A useful synthesis of chloropyrrole-2-carboxylates employed the action of phosphorus pentachloride on pyrrolidin-2-one-5-carboxylates (40) (87CB45) (Scheme 15), and in a Pummerer-type reaction pyrrol-3-yl sulfoxides were transformed by thionyl chloride into chloropyrroles. Yields were increased to >80% by the use of oxalyl chloride (88JOC2634) (Scheme 15). 

Recent advances in the scope and mechanisms of Pummerer-type reactions have been reviewed.133... 

Toda, J., Niimura, Y., Takeda, K., Sano, T., and Tsuda, Y. (1998) General method for synthesis of erythrinan and homo-erythrinan alkaloids (1) synthesis of a cycloerythrinan, as a key intermediate to erythrina alkaloids, by Pummerer-type reaction. Chemical e[ Pharmaceutical Bulletin, 46, 906-912, and literature cited therein. 

BTI is a useful reagent for Pummerer-type reactions of a-acyl sulphides. Instead of being separately oxidized to their sulphoxides, the sulphides were converted in situ into sulphonium salts these subsequently reacted with added aromatics or intramolecularly to afford various products. These reactions were performed in boiling 1,2-dichloroethane and some results are illustrated in Table 4.6. 

Pummerer-type reaction of a-acetylsulphides with BTI Substrate Product Yield (%)... 

Treating A-aryl-2-(benzylthio)benzamides 215 with [bis(trifluoroacetoxy)iodo]benzene containing TFA results in an interrupted Pummerer-type reaction to give 2-aryl-l,2-benzisothiazolo-3(2//)-ones 216 (Scheme 125) <2001H(55) 1231, CHEC-III(4.05.9.1)596>. 

Treatment of chiral, nonracemic vinyl sulfoxides (214) with O-silylated ketene acetal (215) in the presence of a catalytic amount of zinc chloride resulted in an enantioselective additive Pummerer-type reaction, affording the corresponding enantiomerically enriched methyl-4-siloxy-4-sulfenylbuyrate (216) (Scheme 55).122 This is the overall addition of the enolate equivalent to the vinyl sulfoxide. 

F. Carbon-Carbon Bond Formation via Pummerer-Type Reaction... 

Asymmetric Pummerer rearrangement is a very attractive reaction as previously described. In particular, the reactions induced by SKA work well, and may be synthetically exploited in many cases. The results described here demonstrate that the stereoselective a-deprotonation of the sulfoxide is a prerequisite process for asymmetric induction in the Pummerer reaction. Since many kinds of synthetic and enzymatic preparative methods of optically pure sulfoxides have been developed, the present Pummerer-type reaction will be applicable to many other chiral sulfoxides with one a-substituent, chiral vinylsulfoxides and chiral co-carbamoylsulfox-ides, thus leading to enantioselective syntheses of many new bioactive compounds in the near future. 

In the total synthesis of ( )-y-rubromycin, the intermediate benzo[Z>]furan-based pentacyclic ketal illustrated below was made via an aromatic Pummerer-type reaction <07AGE7458>. By reaction of an aryllithium with a phthalide as a key step, another type of spirobiisobenzo [b] furans was made accordingly <07S754>. 

The addition of Grignard reagents to 2-nitrofuran provided rra r-2,3-disubstituted 2,3-dihydrofurans as the predominant isomers <2003TL3167>. 2- and 3-(Phenylsulfinyl)furans underwent Pummerer-type reaction-initiated regioselective nucleophilic additions, as shown in Equation (20) and Scheme 13, respectively <2004OL3793>. 

The reactions of substituents attached to the sulfur atom have been reviewed in some detail in CHEC-II(1996) <1996CHEC-II(3)373>. They are known to undergo silicon Pummerer-type reactions. 

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