Pummerer methyl sulfoxide rearrangement

The Pummerer Rearrangement Pummerer methyl sulfoxide rearrangement... 

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 the Pummerer rearrangement and the Ritter reaction occurs in the reaction of acetonitrile with methyl phenyl sulfoxide (equation 25) in a mixture of irifluoroacetic acid and its anhydride, although a substantial amount of the nonnal a-acetoxylation also occurs. Participation by amido groups is also possible, the interest here being largely in the construction of lactams via the intramolecular cycli-zation mode. Whereas Wolfe and his coworkers were unable to find conditions for the cyclization of S-phenylcysteinamide sulfoxides under Pummerer conditions, Kaneko found that variously substituted... 

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... 

In comparison to some of the other activation methods however, the dimethyl sulfoxide-acetic anhydride procedure has certain disadvantages. The method often requires the use of long reaction times (1 24 h), which can result in many side reactions, especially with sensitive substrates. Notable in this respect is that it is not uncommon for this procedure to result in the formation of substantial yields of the thiomethyl ethers obtained from the Pummerer rearrangement product as described above. In fact upon attempted oxidation of cholesterol with this system, the major product obtained was the corresponding (methylthio)methyl ether. Acetates may also be formed if the alcohol is unhindered. For example the sugar derivative (9) reacts under these conditions to form an enol acetate (derived from the requir carbonyl compound) in 40% yield contaminated with 30% of the acetate (10 equation S). ... 

On warming above -30 C the mixture clears and a Pummerer rearrangement occurs to form (methyl-thio)methyl trifluoracetate (13). However the extent of this by-product formation is minimized at Ae lower temperature, and the reaction with alcohols gives high yields of carbonyl products over short reaction times. This makes trifluoroacetic anhydride one of the better activators for dimethyl sulfoxide oxidations. 

These trihydroxy sulfoxides are useful molecules in total synthesis because of the possible transformation of the sulfoxide into aldehyde by a Pummerer rearrangement. Homoallylic 3-hydroxy sulfoxides have also been prepared from 3-epoxy sulfoxides, readily obtained from methyl monochloroacetate (Scheme 61a). ... 

The synthesis of a-cyclocitral (161) in Scheme 39 illustrates further how trimethylsilyl sulfides can be synthesized and readily converted to aldehydes by the sila-Pununerer reaction. Compound (159) was prepared by a route involving a 2,3-sigmatropic rearrangement of the ylide derived from intermediate U )> The sila-Pummerer rearrangement of the sulfoxide derived from (158) occurred below room temperature. Unfortunately, however, the enhanced rate of the rearrangement to (160) conferred by the methyl substituent on the intermediate sulfoxide was accompanied by greater than normal difficulty in the (2,5-acetal hydrolysis step. 

A simple and straightforward application was outlined in the synthesis of hydrohydrastinine as depicted in Scheme 10. Michael addition of 3,4-methyle-nedioxyphenylmethyl amine to vinyl sulfoxide 36 took place smoothly in refluxing methanol. Pummerer rearrangement in acetic anhydride afforded acetoxysulfide 37 in 90% yield and this was then cyclized to 38 with BF3 etherate in 93 % yield. Sulfide 38, which was rather unstable, was desulfurized with Raney nickel in 80 % yield. Hydrolysis of the acetyl group followed by reductive methy-lation afforded hydrohydrastinine (39) in good yield [24]. 

The Pummerer reaction, whose key step is a [2,3]-sigmatropic rearrangement, has never been observed to lead to efficient transfer of chirality starting from chiral sulfoxides in the presence of acetic anhydride [1632, 1633], A modification via silyloxysulfides, generated with O-methyl-OTBDMS ketene acetal at 65°C, allows asymmetric silicon-induced Pummerer reaction from chiral sulfoxides 10.29 with a high chirality transfer [1634] (Figure 10.11). The ( S)-sulfoxides generate the (5)-secondary ethers and vice-versa. 

C-methyl and 2-C-methyl triacetates (480 and 481), with the latter distinctly prevailing. The same cycle of reactions applied to 479 gave the 5-thiopentose system (482) in low yield. Preparation of the 1,3-phenylboronate ester (483) followed by oxidation to a mixture of stereoisomeric sulfoxides and Pummerer rearrangement proved to be a better way the yield of both regioisomeric 2-C-methyl and 4-C-methyl compounds (484 and 485) was 20%. Compound 485... 

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