Sulfides Pummerer rearrangement

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

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... 

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%. 

The chemical reactivity of sulfoxides as compared with sulfides is much greater. The effect of the sulfinyl group on adjacent methylene protons allows chlorination and the Pummerer rearrangement to take place. The chlorination is stereospecific, resulting in cis products. The Pummerer rearrangement results in two possible isomers (Scheme 2) (55). The Nuphar sulfoxides can be epimerized on carbon C 7 by thermal rearrangement (see Section IV, Scheme 1). 

The first step is just the SN2 displacement of Cl- by RS that you have already seen. The second step actually involves chlorination at sulfur (you have also seen that sulfides are good soft nucleophiles for halogens) to form a sulfonium salt. Now a remarkable thing happens. The chlorine atom is transferred from the sulfur atom to the adjacent carbon atom by the Pummerer rearrangement. 

The Pummerer rearrangement of sulfoxides with acid anhydrides has been extensively utilized as a method for the synthesis of a-substituted sulfides. When a,(3-unsaturated sulfoxides are used, the initial formed oxysulfonium ion may undergo two different pathways the additive Pummerer reaction or the vinylogous Pummerer reaction. The following sections will consider examples from both pathways. 

The generally accepted mechanism6 of Pummerer rearrangement is the one in which there is an initial attack on the sulfoxide oxygen atom by an electrophilic species, e.g., protonation or acylation. Acylation is followed by proton abstraction by a base from the a-carbon atom of the sulfoxide to form an ylide, which rapidly eliminates an acetate anion to form the a-sulfonium salt. Addition of acetate anion to the sulfonium intermediate completes the formation of the a-functionalized sulfide. Ylide formation from sulfoxonium salts is well recognized, and this aspect... 

Among other electrophilic reagents ctq>able of twinging about the Pummerer rearrangement are halides of organic and inorganic acids. As these halides transform sulfoxides into a-chlorosulfides they complement the sulfide chlorination route to these compounds. Thionyl chloride reacts readily with sulfoxides and 3-keto sulfoxides methyl phenyl sulfoxide furnishes chloromethyl phenyl sulfide (equation 37). Benzoyl chloride and acetyl chloride behave similarly. d yanuric chloii is transformed into cyanuric acid by dimethyl sulfoxide, which in turn is transformed into methyl chloromethyl sulfide (equation 3g).54,S5... 

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