Pummerer products/reaction/rearrangements

DMSO or other sulfoxides react with trimethylchlorosilanes (TCS) 14 or trimefhylsilyl bromide 16, via 789, to give the Sila-Pummerer product 1275. Rearrangement of 789 and further reaction with TCS 14 affords, with elimination of HMDSO 7 and via 1276 and 1277, methanesulfenyl chloride 1278, which is also accessible by chlorination of dimethyldisulfide, by treatment of DMSO with Me2SiCl2 48, with formation of silicon oil 56, or by reaction of DMSO with oxalyl chloride, whereupon CO and CO2 is evolved (cf also Section 8.2.2). On heating equimolar amounts of primary or secondary alcohols with DMSO and TCS 14 in benzene, formaldehyde acetals are formed in 76-96% yield [67]. Thus reaction of -butanol with DMSO and TCS 14 gives, via intermediate 1275 and the mixed acetal 1279, formaldehyde di-n-butyl acetal 1280 in 81% yield and methyl mercaptan (Scheme 8.26). Most importantly, use of DMSO-Dg furnishes acetals in which the 0,0 -methylene group is deuter-ated. Benzyl alcohol, however, affords, under these reaction conditions, 93% diben-zyl ether 1817 and no acetal [67]. 

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. 

Tandem, cascade, and other kinds of combined chemical transformations have been shown to be extremely useful in the synthesis of conplex structures. The Pummerer rearrangement can also be combined with different known reactions in order to produce structures more conplex than the usual Pummerer products. Here, we describe two recent applications of Pummerer chemistry in combination strategies. 

The Pummerer reaction of conformationally rigid 4-aryl-substituted thiane oxides with acetic anhydride was either stereoselective or stereospecific, and the rearrangement is mainly intermolecular, while the rate-determining step appears to be the E2 1,2-elimination of acetic acid from the acetoxysulfonium intermediates formed in the initial acetylation of the sulfoxide. The thermodynamically controlled product is the axial acetoxy isomer, while the kinetically controlled product is the equatorial isomer that is preferentially formed due to the facile access of the acetate to the equatorial position . The overall mechanism is illustrated in equation 129. 

Scheme 2.146. Synthesis of several natural products via Pummerer-type rearrangement/ 1,3-dipolar cycloaddition/ring-opening reactions.

The differing nucleophilicity of acetate and trifluoroacetate anion determined the manner in which naphtho[l,8-/yt]-l,5-dithiocinc sulfoxide 127 rearranged on treatment with acetic and trifluoroacetic anhydrides. In both cases, the reaction proceeded through formation of a disulfonium dication 128, but the final products were different. When acetic anhydride was used, the reaction afforded the corresponding a-acetylsulfide 130, a normal product of the Pummerer rearrangement, while trifluoroacetic anhydride caused isomerization with formation of dithioacetal 132 (see Scheme 16) <1995HAC559>. 

The synthesis of the benzoimidazo[l,2- ][l,2,3]thiadiazole 61 can be explained using the same mechanistic model to that used for the Hurd-Mori reaction. The amino benzimidazole 58 when treated with thionyl chloride at reflux affords the benzoimidazo[l,2-r ][l,2,3]thiadiazole 61. If, however, the reactant 58 is treated with thionyl chloride at room temperature, the chloromethyl derivative 59 is formed. This derivative was then transformed into product 61 on reflux with thionyl chloride. The proposed mechanism for the formation of product 61 is for the initial formation of the sulfoxide 60, which then undergoes a Pummerer-like rearrangement, followed by loss of SO2 and HC1 to give the c-fused 1,2,3-thiadiazole 61 (Scheme 7) <2003TL6635>. 

Reaction of -dimethylthiobenzene sulfoxide 56 with trifluoroacetic anhydride results in a mixture of sulfide 65 and the corresponding mono- and disubstituted products of the Pummerer rearrangement 63, 64 via intermediate disulfonium dication 62 (Scheme 23).88... 

The influence of the classical anomeric effect and quasi-anomeric effect on the reactivity of various radicals has been probed. The isomer distribution for the deu-teriation of radical (48) was found to be selective whereas allylation was non-selective (Scheme 37). The results were explained by invoking a later transition state in the allylation, thus increasing the significance of thermodynamic control in the later reactions. Radical addition to a range of o -(arylsulfonyl)enones has been reported to give unexpected Pummerer rearrangement products (49) (Scheme 38).A mechanism has been postulated proceeding via the boron enolate followed by elimination of EtaBO anion. 

The formation of 29, the product of a sila-Pummerer rearrangement, as a minor reaction product points to the intermediacy of the ion pair 28. 

The ease of oxidation depends on the electron availability on the sulfur. In quinoline and pyrimidine analogues of (459) the rate of the reaction is decreased, and in these betaine systems sulfone formation is not observed using peracids in the oxidations. A 2-carboxy group as in (463 R = H) promotes the Pummerer-type rearrangement. The initially formed hemimercaptal mainly eliminates water to give the thiazole (464) a minor product (465) may be formed by ring opening (81H(15)1349). 

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