Thioethers from ketones

SECTION 132 Ethers, Epoxides, and Thioethers from Ketones... 

SECTION 132 ETHERS, EPOXIDES AND THIOETHERS FROM KETONES... 

Alone formed by the reaction of lithium aluminum hydride and aluminum chloride in ether cleaves exclusively the carbon-oxygen bond in cyclic monothioketals derived from ketones and mercaptoethanol, and on refluxing in 100% excess for 2 hours produces -hydroxyethyl sulfides (yields 66-91%) on prolonged heating with the reagent these -hydroxyethyl sulfides are further reduced to the corresponding ethyl sulfides (thioethers) (yields 28-81%) [936]. 

Classification and Organization of Reactions Forming Difunctional Compounds. This chapter considers all possible difunctional compounds formed from the groups acetylene, carboxylic acid, alcohol, thiol, aldehyde, amide, amine, ester, ether, epoxide, thioether, halide, ketone, nitrile, and olefin. Reactions that form difunctional compounds are classified into sections on the basis of the two functional groups of the product. The relative positions... 

Reactions with c/5-ethylene-l,2-di(thioethers) Alkylthioethynylcarbinols from ketones... 

The readily available benzotriazolyl derivative of dimethyl sulfide, compound 821, can be alkylated on a-carbon in a stepwise manner to provide (a,a-disubstituted)alkyl thioethers 823 (Scheme 131). Hydrolysis of these thioethers under mild conditions (5% H2S04 at room temperature) furnishes ketones 824 in high yields. The anion derived from mono substituted (benzotriazol-l-yl)methyl thioether 822 adds to butyl acrylate to give intermediate 826 that can be hydrolyzed to y-ketoester 825. In another example of reactivity of a-(benzotriazol-l-yl)alkyl thioethers, treatment of thioether 822 with BunLi followed by phenyl isocyanate converts it into a-ketoanilide 828, via intermediate adduct 827 <1998JOC2110>. 

Treated with ZnBr2 followed by enamines, phenyl thioethers 829 derived from aryl aldehydes are converted to (l-(phenylthio)alkyl ketones or aldehydes 830 in moderate to good yields (Equation 19). Enamines used in these syntheses are (1) morpholine enamine derived from diethyl ketone, (2) diethylamine enamine of propiophenone, (3) piperidine enamine derived from isovaleraldehyde, and (4) pyrrolidine enamine of cyclohexanone <2000H(53)331>. 

The reactions of the corresponding propargyl sulfoxides and sulfones now resemble the chemistry of the other acceptor-substituted derivatives such as ketones and aldehydes (see Section 1.2.4). Compared with the thioethers, here much milder bases are sufficient apart from aluminum oxide, often triethylamine or potassium carbonate are used. Sometimes even a spontaneous isomerization takes place. The selective isomerization of one triple bond in the presence of a second triple bond in 126 [313] (Scheme 1.56) or an allyl sulfone in 129 [314] (Scheme 1.57) are just two examples out of a whole series [178, 304, 313, 315-331]. When, on the other hand, the in situ oxidation of 126 was carried out in an aprotic solvent, no isomerization at all was observed. 

An effective and mild electrocatalytic procedure for the deprotection of the 1,3-dithiane group of (68), giving the ketone (67), has been developed by using a small amount of tris(/ -tolyl)amine as a homogeneous electron-transfer catalyst (Scheme 26) [86]. The scope and limitations are discussed in detail [87]. The method can be applied also for oxidative removal of the 4-methoxybenzyl thioether protecting group from poly-cystinyl peptides [88]. 

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