In the Pummerer

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-... 

Recently, new examples of asymmetric induction in the Pummerer reaction of chiral sulfoxides have been described. Oae and Numata (301) reported that the optically active a-cyanomethyl p-tolyl sulfoxide 275 undergoes a typical Pummerer rearrangement upon heating with excess of acetic anhydride at 120°C, to give the optically active a-acetoxy sulfide 276. The optical purity at the chiral a-carbon center in 276, determined by means of H- NMR spectroscopy using a chiral shift reagent, was 29.8%. 

A similar extent of asymmetric induction was observed (88) in the Pummerer reaction of optically active a-phosphoryl sulfoxide 49, which results in the formation of the corresponding optically active a-acetoxy a-phosphorylmethyl sulfide 277. 

DCC) proceeds with much higher enantioselectivity (e.e. up to 45%). Likewise, a much higher degree of asymmetric induction was observed in the Pummerer reaction of optically active a-carbonyl-substituted sulfoxides carried out in the presence of DCC (303) to give the a-acetoxy-a-p-toluenesulfenylacetic acid derivatives 278. 

As previously described, the effect of substituent groups on the silyi function is an important factor in terms of determining the reaction course. Table 4 shows the ratio of the products in the Pummerer reaction using various SKAs.33 These results suggest that carbon-carbon bond formation preferentially occurs when using a small silyi function such as the trimethylsilyl function. This tendency was observed in another substrate which has asymmetric carbon at the (3-position of the sulfur atom (Table 5).33 Interestingly, the syn-selectivity of the rearrangement product... 

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. 

Vankar and Rao have shown that the cationic intermediate (126) in the Pummerer reaction can be intercepted by nitriles producing the amido sulfides (127). The moderate yield of these novel products is a consequence of competition with the normal Pummerer process (Scheme 63). 

Although the emphasis in this chapter is placed on the use of acid anhydrides in the Pummerer reaction, a number of other activating reagents, e.g. acids, in particular p-toluenesulfonic acid, and trial-kylsilyl halides, have been employed. Mention of these reagents is made in cases where their use leads to an improvement in yields or selectivity, or to a transformation which is not possible using an acid anhydride. Acetyl chloride is usually not employed in the Pummerer reaction because of the simultaneous presence of acetate ion and chloride ion in the reaction medium. The product of these reactions is predominantly the thioacetal derived from spontaneous decomposition of the initially formed a-acetoxy sulfide. 

Compound (116) is obtained in 41% chemical yield and 67% ee, one of the highest reported cases of asymmetric induction in the Pummerer reaction. The use of a silicon activating reagent in this reaction is crucial as the reaction of sulfoxide (115 R = Me) with trifluoroacetic anhydride gave compound (119), presumably via intermediates (117) and (118). This latter result points to the possibility that this and... 

Non-nucleophilic activating agents, such as p-toluenesulfonic acid, are generally used to generate the intermediate thionium ions. The use of trifluoroacetic anhydride in the Pummerer step of the kopsanone synthesis is feasible, since at elevated temperatures an equilibrium is established between the thionium ion and trifluoroacetoxy sulfide intermediates. Trifluoroacetic anhydride in combination with a Lewis acid can also be used. Under these latter conditions efficient intermolecular reactions of acylthionium ions with aromatic systems are observed. ... 

Numata, T., Ito, O., Oae, S. Unusually high asymmetric induction in the Pummerer reaction of optically active sulfoxides. Tetrahedron Lett. 1979, 1869-1870. 

Other ji-bonds were also found to efficiently participate in the Pummerer/Mannich cascade. For example, allylsilane 303 gave bicycle 304 in 61% yield when heated with /7- l sO11 (equation (7)). The terminal alkene present in 305 cyclized to give 306,... 

The benzo derivatives (41) and (42) of the disulfide dication (36) can also be prepared in the reaction of the corresponding 5 -oxides with cone. H2SO4. However, since the resulting bis(hydrogen-sulfate) salts are very hygroscopic, the structures are identified only on the basis of elemental analyses. The dication (36) is an intermediate in the Pummerer reaction of the S -oxide (37) with acetic anhydride, shown in Scheme 12, giving the a-acetoxylated product (43). However, when trifluoromethanesulfonic anhydride is used instead, the dication (36) can be isolated as a triflate... 

Acid anhydrides and/or acids are employed in the majority of synthetic applications of the Pummerer reaction. However, there are a number of other reagents which activate the sulfoxide oxygen in the Pummerer reaction. The use of organosilicon reagents is discussed in Sections 4.7.3.3,4.7.3.S and 4.7.3.7 in connection with the preparation of trimethylsiloxy sulfides and vinyl sulfides. Recently it was shown that the trimethylsilyl ester of polyphosphoric acid also promotes the Pummerer rearrangement. 

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