Thioethers, reduction

Sulfur Substituents. Acetylation and alkylation of pyridinethiones usually take place on sulfur (39). An exception to this is 4-pyridinethione [19829-29-9] which is acetylated on nitrogen. Displacement of thioethers can be achieved with hydroxide or amines (eq. 13) (40). Thioether functional groups can also be removed by reduction (39). 

Pyrrolethiols, readily obtained from the corresponding thiocyanates by reduction or treatment with alkali, rapidly oxidize to the corresponding disulfides. They are converted into thioethers by reaction with alkyl halides in the presence of base. Both furan- and thiophene-thiols exist predominantly as such rather than in tautomeric thione forms. 

The reduction of aromatic sulphoxides into the corresponding thioethers appears to be general it occurs at a lead cathode72, in alcoholic sulphuric acid solution72 and also in the presence of tetraalkylammonium salts73,74. Data in DMF are also available, when phenol is used as a proton donor. 

The thioether functionalized bisphosphonates, 7 and 8, upon reduction with LiAlH4 produced the corresponding S2P2 and S3P2 primary bisphosphine frameworks 9 and 10 respectively in good yields (Scheme 4) [47,48]. 

In 1994, the scope of this p-hydroxy sulfoximine ligand was extended to the borane reduction of ketimine derivatives by these workers. The corresponding chiral amines were formed with enantioselectivities of up to 72% ee, as shown in Scheme 10.57. It was found that the A -substituent of the ketimine had a major influence on the asymmetric induction, with a ketoxime thioether (SPh) being the most successful substrate. 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

The interest in low-valent Ni complexes in S-rich environments has been stimulated by the presence of Ni in [Ni,Fe] hydrogenase and CODH. While thiolate ligation usually favors higher oxidation states, thioethers stabilize Ni1 and Ni°. In most cases, however, Ni1 ions of an NiS4 chromophore are unstable with respect to disproportionation. The cyclic voltam-mogram of square planar (983) with homoleptic thioether coordination exhibits a quasi-reversible wave at —0.42V (vs. NHE), which on the basis of the rhombic EPR spectrum (gi 2.27, g2 2.11, and g3 2.03) of the chemically reduced species (Na/Hg) is assigned to metal-centered reduction. 8... 

As the final example in this section, a Li-mediated carboaddition/carbocycliza-tion process will be described. Thus, Cohen and coworkers observed a 5-e%o-trig-cy-clization by reaction of the lithium compound 2-349 and a-methyl styrene 2-350 to give 2-352 via 2-351 (Scheme 2.82). Quenching of 2-352 with methanol then led to the final product 2-353 [189]. In this process, 2-349 is obtained by a reductive lithia-tion of the corresponding phenyl thioether 2-348 with the radical anion lithium 1-(dimethylamino)naphthalenide (LDMAN) (2-354). Instead of the homoallylic substance 2-348, bishomoallylthioesters can also be used to provide substituted six-membered ring compounds. 

Of particular note here is that, besides the organolithium derivative, the solvent also plays an important role [191] Me20 was found to be a highly effective for the in-situ production of the radical anion 2-354 from its precursor N,N-dimethylammo naphthalene. For the reductive lithiation of the thioethers and the following steps, the addition of pre-cooled Et20 combined with subsequent removal of the Me20 under reduced pressure gave the best results. 

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