Phenylthio group

Diphenylthioalkanes react with mercuric fluoride to give 1-fluoro-l-phenylthio-alkanes. Provide a detailed description of a likely mechanism for this reaction. Consider such questions as (1) Is an SnI or an Sn2 process most likely to be involved (2) Would NaF cause the same reaction to occur (3) Why is only one of the phenylthio groups replaced ... 

Contrary to the expectation that a sulfur-containing substituent will be a catalyst poison, a phenylthio group serves as an effective selectivity control element in TMM cycloadditions. A single regioisomer (30) was obtained from the carbonate precursor (31) in good yield. The thermodynamically more stable sulfide (32) is readily accessible from (30) via a 1,3-sulfide shift catalyzed by PhSSPh. A wide array of synthetically useful intermediates could be prepared from the sulfides (30) and (32) with simple transformations (Scheme 2.10) [20]. 

Substituted TMM complexes also cycloadd to aldehydes in the presence of a tin cocatalyst such as MesSnOAc and MesSnOTs [31]. Reaction of 2-heptenal with methyl precursor (6) gave a mixture of methylenetetrahydrofurans (68) and (69). This regioselectivity is reversed with 10-undecenal and methyl precursor (5), where adduct (70) now predominates over (71). As in the carbocyclic system, the phenylthio group also functions as a regiocontrol element in reaction with cyclohexyl aldehyde. The initially formed adduct (72) eliminates the element of thio-phenol on attempted allyl rearrangement, and the overall process becomes a cycloaddition approach to furans (Scheme 2.21) [20]. 

Introduction of the phenylthio group onto the 5-carbon atom of alcohols can have valuable synthetic applications. 5-Phenylthio alcohols can be oxidized to the corresponding 5-sulfoxides and sulfones (with their versatile reactivities) or they can be deprotonated by strong base converting the 5-carbon atom to a nucleophilic species. Conversion of 5-phenylthio alcohols to the corresponding 5-carbonyl compounds can be achieved via halogenation followed by subsequent hydrolysis. In this way an inversion of the reactivity of the 5-carbon atom may be accomplished and it can react as an electron acceptor. 

Nicolaou and coworkers reported a new method for preparing glyco-syl fluorides (38) from phenyl thioglycosides (37) by treatment with di-ethylaminosulfur trifluoride (DAST)-A -bromosuccinimide (NBS), or HF-pyridine-NBS, the phenylthio group of the thioglycosides being initially activated by NBS. Thus prepared were compounds 39, 40, and 42 (see Table I) and 3,4-C)-carbonyl-2,6-dideoxy-3-C-methyl-L-n Z)ohexo-pyranosyl, 2-azido-2,6-dideoxy-3,4-0-isopropylidene-D-altropyranosyl,... 

Bromomethyl-6,7-dichloro-3-phenylthioquinoxaline 1,4-dioxide (245, Q = SPh, R = Br) gave 6,7-dichloro-2-(2-hydroxyethylamino)-3-(2-hydroxyethy-lamino)methylquinoxaline 1,4-dioxide (245, Q = R = NHCH2CH2OH) (H2NCH2CH2OH, CHCI3, 20°C, 4 days 62% note concomitant aminolysis of the phenylthio group).483... 

A more recent approach, which also profits from the synthetic versatility of stabilized thionium ions, has been elaborated by Berard and Piras [22]. These authors observed that the cyclobutane thionium ions 1-76 obtained from the cyclopropyl phenyl sulfides 1-75 by treatment with pTsOH under anhydrous conditions can be trapped by an adjacent electron-rich aromatic ring to give the chromane derivatives 1-77 in good to excellent yields (Scheme 1.20). As expected, 1-77 were obtained as single diastereoisomers with a ds-orientation of the methyl and the phenylthio group as a consequence of steric constraints. 

Homoallyl ethers or sulfides.1 gem-Methoxy(phenylthio)alkanes (2), prepared by reaction of 1 with alkyl halides, react with allyltributyltin compounds in the presence of a Lewis acid to form either homoallyl methyl ethers or homoallyl phenyl sulfides. Use of BF3 etherate results in selective cleavage of the phenylthio group to provide homoallyl ethers, whereas TiCl effects cleavage of the methoxy group with formation of homoallyl sulfides. 

Recently Ikegami used the thiol addition reaction in the preparation of optically pure 4-phenylthioazetidin-2-one, the starting material for an elegant ( + )-thienamycin synthesis (58). When 4-phenylsulfonylazetidin-2-one was treated with cinchonidine and thiophenol, the intermediate azetinone underwent a thiol addition reaction and the 4-phenylthioazetidin-2-one was obtained in 54% optical and 96% chemical yield (eq. [13]). Recrystallization of the optically active aze-tidinone allows isolation of the pure enantiomer from the mother liquor. The phenylthio group is eliminated later in the synthesis of thienamycin. 

Partial fluorination of 4-arylthio-l,3-dioxolan-2-ones occurs preferentially at the carbon atom adjacent to the thio group [67]. However, a remarkable solvent effect is encountered. In the more polar solvent, dimethoxyethane substitution occurs, while in the less polar dichloromethane a larger portion of the desulfurization with cleavage of the phenylthio group takes place. This is attributed to the fact that the intermediate radical cation is more stable in the polar solvent and undergoes deprotonation, while in the less polar solvent, the less stabilized radical cation dissociates into a dioxolane cation and a phenylthio radical. 

Among the electron-rich alkenes, vinylsulfides are especially amenable to cation-radical reduction an important feature is the absence of hydrogenolysis of carbon-sulfur bonds. The reduction of [(phenylthio)methylene]cyclohexane is efficient (88%), and the retention of the phenylthio group clearly contrasts with catalytic hydrogenation (Mirafzal et al. 1993). This provides versatile functionality for further synthetic operations. 

Noteworthy is that by treating tellurothioalkene with n-BuLi, the phenylthio group remains untouched, showing the greater reactivity of vinyltelUuride towards vinylsulphide (eq. (4)). 

Displacement of a phenylthio group by lithium using LiDBB at —78°C was found to be effective for the preparation of a /ra r-4-lithio-l,3-dioxane configurationally stable at that temperature. Reaction with alkyl halides with retention of the configuration afforded the /ra r-dioxanes with 99 1 selectivity. Equilibration of the trans-configurated 4-lithio-l,3-dioxane to the thermodynamically more stable r-derivative was achieved upon warming the solution to —20 °C. The transjcis-ratio was approximately 1 5. This ratio was also found after alkylation with alkyl halides (Scheme 60) <1999JOC6849>. 

A study of the alkylation of the trimethylsilyl enol ether of octahydro-1 (2//)-naphthalenone reveals that the diastereoselectivity of the reaction is similar to that of the methylation of the corresponding lithium enolate (see Section 1.1.1.3.1.1.2 1.)89. Lewis acid cataly2ed phenyl-thioalkylations of the type indicated (i.e., 3 -> 4) have been used for a-alkylations of several cyclic and acyclic ketones, as well as aldehydes89. The easy removal of the phenylthio group by catalytic hydrogenation completes this convenient procedure for a-alkylation of carbonyl compounds89. 

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