Sulfoxides activated methylenes

The condensation of aromatic and aliphatic aldehydes with sulfoxide-activated methylenes like phenylsulfmylacetonitriles and phenylsulfmylacetates selectively forms a-sulfinyl-a,3-unsaturated carbonyl compounds (144) with the alkyl or aryl group trans to the sulfinyl group (see Section 1.11.2.5). 2 Oxidations of (144) with m-chloroperbenzoic acid yield the unsaturated ( )-sulfones... 

In addition to the application of malonic esters, four-membered ring compounds can also be realized by using methyl methylsulfanylmethyl sulfoxide (14) as the active methylene component.25 27 As demonstrated in the following scheme, when the potassium salt of methyl methylsulfanylmethyl sulfoxide is allowed to react with 1,3-dibromopropane, cyclobutanone dimethyl dithioacetal 5-oxide (16) is isolated in 97% yield.8,10 Of particular interest is that the... 

A careful analysis of the structure-activity results in phenols containing another benzene nucleus linked directly or through a sulfide, sulfoxide or methylene... 

Cottrell et al. at Merck Sharp and Dohme Research Laboratories reported a mild procedure that used potassium carbonate in dimethyl sulfoxide. These conditions were compatible with highly functionalized benzyl azides, and extended the substrate scope of active methylene compounds to acetoacetone and benzoylacetone. This extension provided access to acyl-1,2,3-triazoles 21 for the first time via the Dimroth triazole synthesis. 

Active methylene compounds are known to undergo condensation with alkyl halides to give excellent yields of dialkylated products under phase transfer conditions.1 5 we have extended the phase transfer catalyzed alkylation to polycondensation of active methylene compounds such as -butyl cyanoacetate and phenylacetonitrile with activated dichlorides, and successfully synthesized carbon-carbon chain polymers with high molecular weights. Other types of carbon-carbon chain polymers of rather low inherent viscosities were already prepared by the solution polycondensation of malononitrile with bischloromethyl aromatic compounds in dimethyl sulfoxide using sodium hydridel5 or triethylaminel as a base. 

Linear polymers can be obtained by the base-catalyzed condensation of compounds possessing active methylene groups with compounds possessing carbonyl groups. An example is shown in Eq. (1-2) (20-23). Anhydrous ethanol, dioxane, dimethylformamide, and dimethyl sulfoxide were suitable solvents. Low molecular weight polymers were obtained that had predominately aldehydic termination. The insolubility and infusibility of the polymer shown in Eq. (1-2) led to the belief that it was not linear (33). Cross-linking... 

These results show that chemical yields are generally higher than for most aldol-type additions of ester cnolates. mainly because of the chemical activation of the methylene group by the sulfoxide, which makes this reaction suitable for any aldehyde or ketone. High asymmetric induction is also generally observed. The aldol adducts obtained by addition to aldehydes have been transformed into optically active four- and five-membered lactones38. 

Recently, optically active (+)-(R)-methy 1 tolyl sulfoxide 102, R = H was alkylated with a very high diastereoselectivity136. The sulfoxide was treated with either lithium diisopropy-lamide (LDA) or lithium tetramethylpiperidide (LTMP) to form the lithio-derivative, which upon subsequent reaction with lithium a-bromomethyl acrylate gave a mixture of two diastereomers of a-methylene-y-sulfinylcarboxylic acid 103. The use of the sterically highly hindered base, LTMP, gave the product with a higher diastereoselectivity. For example, the Sc4 Rc4 ratio was 95 5 when R was the methyl group. 

Further examples of the utility of the allylic sulfoxide-sulfenate interconversion in the construction of various biologically active natural products include intermediates such as the /Miydroxy-a-methylene-y-butyrolactones (e.g. 63)128 and tetrahydrochromanone derivative 64129. Interestingly, the facility and efficiency of this rearrangement has also attracted attention beyond the conventional boundaries of organic chemistry. Thus, a study on mechanism-based enzyme inactivation using an allyl sulfoxide-sulfenate rearrangement has also been published130 131. 

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