Sulfides, 3-keto reduction

The substrate for 5-thiopentose was obtained by intramolecular aldol condensation of diacetonyl sulfide (476). Reduction of the keto group in 477 afforded trans and cis diols (478 and 479 1.3 1) in 85% yield. Acetylation of 478, oxidation to sulfoxide, and Phimmerer rearrangement gave both regioisomeric... 

The carbopalladation is extended to homoallylic amines and sulfides[466. Treatment of 4-dimethylamino-l-butene (518) with diethyl malonate and Li2PdCl4 in THF at room temperature leads to the oily carbopalladated complex 519, hydrogenation of which affords diethyl 4-(dimethylamino) butylmalonate (520) in an overall yield of 91%. Similarly, isopropyl 3-butenyl sulfide (521) is carbopalladated with methyl cyclopentanonecarboxylate and Li2PdCl4. Reduction of the complex affords the alkylated keto ester 522 in 96% yield. Thus functionalization of alkenes is possible by this method. 

The last synthesis to evolve which is due to Ito and his coworkers is interesting in that it relies on a stereospecific skeletal rearrangement of a bicyclo[2.2.2]octane system which in turn was prepared by Diels-Alder methodology (Scheme XLVIII) Heating of a toluene solution of cyclopentene 1,2-dicarboxylic anhydride and 4-methylcyclohexa-l,4-dienyl methyl ether in the presence of a catalytic quantity of p-toluenesulfonic acid afforded 589. Demethylation was followed by reduction and cyclization to sulfide 590. Desulfurization set the stage for peracid oxidation and arrival at 591. Chromatography of this intermediate on alumina induced isomerization to keto alcohol 592. Jones oxidation afforded diketone 593 which had earlier been transformed into gymnomitrol. 

Enantioselective reduction of jS-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity (Figure 3.11). The facile and enantioselective method to prepare optically active 1,3-amino alcohols has been used to prepare 3-aryloxy-3-arylpropylamine type antidepressant drugs, for example (l )-fluoxetine. 

High-quality albuterol was obtained in good yield from this process. However, several environmental disadvantages were identified. The preparation of the keto aldehyde hydrate (KAH) generated dimethyl sulfide, methyl bromide, and trimethyl-sulfonium bromide (this compound sublimed in the condenser). In addition, reduction of the Schiff base with dimethylsulfide borane, although very attractive in simplifying... 

The lower reactivity of Raney Ni towards sulfones allows the chemoselective desulfurization of (4) with Raney W-2, but an appreciable amount of reduction of keto groups was observed. Raney Ni W-2 also tolerates sulfonamides in this work an ionic mechanism was suggested in order to explain the substitution reaction observed. Lactones,keto lactones," and unsaturated lactoneswere tolerated during the desulfurization of sulfide or dithioketal" groups, but deactivated (e.g. by acetone) Raney Ni was generally used. In contrast, carbon-halide bonds are cleaved where the desulfurization is stereoselective only because the product is the thermodynamically more stable d5-lactone (equation 2)." e-" f... 

The preparation of disubstituted epoxides is similarly accomplished by the addition of nucleophiles to more highly substituted ketones. Selective reduction of keto sulfides with either L-Selectride or zinc... 

Interestingly, the a-acetoxy sulfides (106) obtained from the reaction of 3-keto sulfoxides with acetic anhydride containing sodium acetate undergo in situ oxidation-reduction and acyl transfer, giving a-acetoxy thiol esters (107) as products (Scheme 23)J Yields in this process are generally high. 

Dihydro-1,4-benzothiazines have been prepared in good yield by catalytic reduction of / -keto sulfides at elevated temperatures and pressures using a variety of catalysts.78... 

Coutts et al. unsuccessfully attempted to prepare benzothiazines by reductive cyclization of /J-keto sulfides with sodium borohydride or palladium-charcoal. They isolated only the/ -(2-nitrophenylthio) alcohols,136 in contrast to the successful synthesis of the desired ring by the same reduction of /J-(2-nitrophenylthio) esters.128 A wide range of /3-keto sulfides has been successfully reduced to dihydro-1,4-benzothiazines, using tin and hydrochloric acid, in either glacial acetic acid or ether solution.21... 

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