A-Methylthio ketones

The chlorosulfonium compounds can also be used for the synthesis of oxindoles, the stable tautomeric form of 2-hydroxyindoles. The a -methylthio ketone is replaced by ethyl methylthioacetate and the products of the Sommelet-Hauser rearrangement are cyclized to 3-methylthiooxindoles. The methylthiooxindoles are reductively desulfurized with Raney nickel (equation 102) (74JA5508). 

Reduction of a-methylthio ketones, a-Methylthio and a-phenylthio ketones (1) are reduced with high selectivity to sy/i-alcohols (2) by this complex hydride, except when... 

Dual functionalization of alkenes with dimethyl(methylthio)sulphonium tetrafluoroborate and dimethyl sulphoxide gives a-(methylthio)-ketones in excellent yield [equation (37)]. ° Experimentally, the transformation appears to be simple, employing very mild conditions. 

Acyl-2-methylthio-l,6,6a lv-trithiapentalenes, on reaction with mercuric acetate, undergo a degradation leading to a dithiolylidene ketone (Eq. 16).46... 

In contrast to these results, it has been demonstrated that a-(methylthio)tosylhydrazone monoanions, formed by reaction of an initially formed dianion with dimethyl disulfide, undergo in situ dianion formation rather than elimination, to give vinyl sulfides (Scheme 71 ). Since vinyl sulfides can be hydrolyzed to ketones, this sequence constitutes a very effective 1,2-carbonyl transposition. 

Friedel-Crafts reaction of arenes with a-chloro-a-(methylthio)acetophenones [19], When A -phenylbenzimidoyl chlorides are aroylated with an aryl halide in the presence of a catalytic amount of an azoliuni salt (such as 1,3-dimethylimidazolium iodide) and sodium hydride, followed by acid treatment in TUF, unsymmetrical benzils can be isolated in 80-92% yields [201. Added to this method is the sequence ketone enaminoketone a-diketone, which cleaves a carbon-carbon double bond in the final stage by photooxygenation [21]. 

Aryl-substituted ketones react directly with elemental sulfur in hexa-methylphosphorus triamide with formation of l,2-dithiole-3-thiones.46,47 Aryl-substituted acetaldehydes can condense likewise with carbon disulfide to give the analogous 4-aryl-substituted l,2-dithiole-3-thiones.48 The same reaction was observed with aryl-substituted acetic acid esters, in which a methylthio group is incorporated into the reaction product (26).49 Thioketones and enthioles react analogously. 50,51 The parent l,2-dithiole-3-thione (27) has been prepared from the tetra-methyl acetal of malondialdehyde and phosphorus pentasulfide.52 In the presence of ammonia the reaction of cyclohexanone or cycloheptanone with carbon disulfide and sulfur gives as by-products the condensed 1,2-dithiole-3-thiones 28a and 28b, respectively.53... 

In the Nenitzescu synthesis of 5-hydroxyindoles, an A-aryl substituted amino-propenoic ester may be used, albeit with a low yield of product [2343]. Better yields may be obtained by reacting the quinone at ambient temperature with an enaminonitrile [3246]. The methylthio group may be removed by heating with Raney nickel. Magnesium methyl carbonate is sometimes used to carboxylate a methyl ketone but when it is warmed with the methyl ketone (35.3), it causes cyclization of the keto side-chain [2747]. A dioxopyrimidine aldehyde (35.4) is cyclized in moderate yield by heating with carbonate in DMF [2668]. 

A pyridin-2-one ring is formed by reacting a 3-aminodiazine with a reactive malonate ester such the 2,4,6-trichlorophenyl ester this cyclization needs a temperature of about 240 °C to be maintained for about 20 min [3676]. The ease of displacement of a methylthio group in compounds such as (53,8) demonstrates their usefulness a second molecule of the arylamine reacts with the methoxycar-bonyl group [3690]. An alternative method (to that described in Chapter 9, Section II.2) of synthesizing pyridazino[4,S-6]quinolin-10-ones which avoids the use of fluorophenyl ketones is oxidative cyclization of 2-aminophenyl ketones... 

Methoxy-a-(phenylthio) ketones, e.g., 3-methoxy-l-phenyl-2-phenylthiopropanone and 5-methoxy-l-phenyl-4-phenylthio-l-penten-3-onc (Table 6), can also be reduced with syn selectivity by zinc borohydride. calcium borohydride and lithium triethylborohydride82. For zinc and calcium borohydride, at least, it is reasonable to suppose that the transition state 4 (where R3 = MOM) is reinforced by /1-chclation. These reagents are actually more successful than L-Selectride in the reduction of 3-methoxy-1-phenyl-2-phenylthiopropanone, where the L-Se-lectridc result is anomalously poor. A /5-hydroxy substrate, 3-hydroxy-2-mcthylthio-l-phenyI-propanone, could be reduced to 2-methylthio-l-phenyl-l,2-propanediol with good syn selectivity using zinc borohydride (yield 65% d.r. 93 7)81. 

The wH/f-selective reduction of a-alkylthio ketones is less straightforward. Zinc borohydride has been used successfully in some cases, implying that chelation control involving an alkyl(or aryl)thio group is possible. However, the method is not general, as illustrated by the results in the zinc borohydride reductions of 3-methyl-2-methylthio-l-phenylbutanone and 4-methyl-3-phenyl thio-2-pentanone 81. 

Bromo-l,4-diphenyl-3-methylthio-S-triazolium bromide, 53-54 d-Bromoenamines, 71 a-Bromoethyl ethers, 459, 496 vic-Bromofluoroalkanes, 53 Bromohydrins, 52 a-Bromo ketones, 52-53, 150, 406 Bromolactonization, 421, 423... 

Reductive sulfeuyiation. Gassman et al. have found that] Stork s method for reductive alkylation of a,/3-unsaturated ketones (1, 601-602) is applicable to reductive sulfenylation of cyclic a, 3-unsaturated ketones and has the advantage of regiospecificity in the formation of ra-methylthio ketones. Furthermore, the reaction proceeds with some preference for axial attack. 

Bis(methylthio)-a, -unsaturated ketones react with ethyl bromoacetate in the presence of base to give 3-methylthiofurans (Equation (23)) <89T763l> alkyl oxirans are intermediates. 

Pyrolysis of sulfoxides provides a convenient method for introducing unsaturation at the position a- to carbonyl compounds. Formation of the enolate and reaction with dimethyl (or diphenyl) disulfide gives the a-methylthio (or phenylthio) derivative. Oxidation with a suitable oxidant, such as mCPBA or NaI04, gives the sulfoxide, which eliminates sulfenic acid on heating to give the a,(3-unsaturated carbonyl compound. For example, the methyl ester of a pheromone of queen honey bees was synthesized from methyl 9-oxodecanoate after initial protection of the ketone as the acetal (2.24). The -isomer usually predominates in reactions... 

A full report has appeared on the direct lithiation of NN-di-isopropylformamide by t-butyl-lithium and the use of the acyl carbanion thus obtained in the synthesis of a-keto-amides. The lithium enolate of NN-dimethylacetamide has been isolated for the first time, as a white solid, and has been shown to react well with a usual range of electrophiles. A Canadian group have also discussed the synthesis and reactions of such enolates, in particular their behaviour with ketones from which 70% yields of jS-hydroxyamides can routinely be obtained. " These enolates when generated as in the above methods, using lithium di-isopropylamide, also afford good yields of a-(methylthio)-amides when treated with dimethyl disulphide, in contrast to when sodium in liquid ammonia is used as base, which results in polysulphenylation of the amide. ... 

Methyl Methylthiomethyl Sulfone. Methyl methyl-thiomethyl sulfone is the 5-methyl analog of MT-sulfone and it is conveniently synthesized by oxidation of methyl methylthiomethyl sulfoxide (FAMSO) with potassium permanganate or H202-Na0H. It is useful for synthetic methods similar to those using MT-sulfone synthesis of carboxylic esters, ketones, and a-aLkoxy- -arylacetates. In the reaction of this reagent with allylic bromides, a-methylthio- /,5-unsaturated sulfones are obtained by stirring the bromide with potassium carbonate and potassium iodide in hexamethylphosphoric triamide (eq 14), which does not occur with MT-sulfone. 

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