Nucleophilic substitution sulphur compounds

Ghosh and coworkers [109] have reported the development of a novel class of HIV-1 protease inhibitors which incorporate a cyclic sulphone moiety for binding to the P2 subsite. For the provision of cis-2-alkyl-3-hydroxy-tetrahydrothiophene building blocks (for example, 85), Sharpless epoxida-tions of ( )-4-methyl-2-penten-l-ol under catalytic conditions with (+)-diethyl L-tartrate and gave epoxy alcohol (86) of 90% ee (Scheme 5.37). Several steps were then required to access compound (85), including cyanide-induced Payne rearrangement and introdution of sulphur by a double nucleophilic substitution. The (5,S)-antipode of compound (85) was accessed via Sharpless epoxidation using (-)-diethyl D-tartrate. 

Thermal decomposition of / -substituted sulphoxides of the type (426) leads to olefins by nucleophilic attack of phosphorus on sulphur. Compound (426) is conveniently prepared from lithiomethylsulphinyl carbanion and a non-enolizable carbonyl compound followed by treatment with phosphorochlorid-ite. A similar elimination takes place using phenylthiomethyl-lithium, PhSCHgLi, instead of (427). ... 

A series of 7-substituted norbornadienes have been synthesized by quenching the 7-norbornadienyl cation with various nucleophiles of sulphur (SMOj), arsenic (AsPhj), and antimony (SbPhg). 7-t-Butylnorbornadiene, prepared by reaction of t-butyl-lithium with 7-t-butoxynorbornadiene, has been transformed to, inter alia, (128) and (129). By a similar route, (20) and related compounds, required for study of their photoelectron spectra, were prepared (Scheme 5). Propenylidene-norbornadienes were accessible by the routes shown in Scheme 6. They provide a novel photochemical synthesis of dihydro-azulenes, azulenes, and of vinylogous heptafulvenes. 

An examination of a large series of compounds showed that when R and R are electron-withdrawing substituents, rate accelerations are experienced, and in unsymmetrically substituted thioncarbonates the rearrangement occurs primarily in the direction of the ring bearing the more electron-withdrawing substituents. The reaction thus originates from the nucleophilic character of the sulphur. A kinetic study showed that... 

Steric rate enhancement due to hindered rotation was found to be present in ortho-substituted compounds in this series . The relatively low temperature required results from increased nucleophilicity of the sulphur, since the polarization is assisted by the dialkylamino group, towards the zwitterionic form 80. 

Reactions.— The nucleophilic reactivity of the thiocarbonyl sulphur atom in thioureas has been further exemplified in a series of papers reporting on S-alkylation reactions of open-chain " as well as cyclic thioureas using alkyl halides. Ried and his co-workers have reported that (4-quinazolyl)thioureas (315) react smoothly with methylene iodide in the presence of triethylamine to yield the 1,3-thiazetidines (316). The ready formation of (316) was attributed to the special effect of the intramolecular hydrogen bonding in (315), as common thioureas usually did not enter into this reaction in a well-defined and profitable way. 5,5-Diphenyl-2-thio-hydantoin reacted with symmetrical ao>-dibromo-alkanes to yield the cyclization products (317). The action of excess of methyl iodide on N -substituted N-(o-aminophenyl)thioureas afforded the benzimidazoles (318), alternatively obtainable by treatment of the same thioureas with mercuric chloride." " In a similar manner, l-amino-6,7-dimethoxy-3,4-di-hydroisoquinolines were formed by the action of mercuric chloride on the thioureas (319)" or their S-methyl derivatives (320). " A recent paper by Klayman and his co-workers deals with the reactivity of S-methiodide derivatives of thioureas that are activated by electron-withdrawing groups towards hydroxylic compounds. "... 

There have been a number of reports on the photochemical reaction between diazo-compounds and sulphides to form either stable or transient ylides. lllger et al. reported the isolation of a series of ylides from the reaction of dimethyl sulphide with substituted diazomethanes, such substituents being carbonyl, sulphonyl, or phosphoryl groups. Ando et of. described the reaction of diazo dimethyhnalonate with a series of sulphides but found that the yields of ylides varied considerably, much more so than for the thermal reaction, with the nucleophilicity of the sulphide. For example, dimethyl sulphide afforded an 88% yield of ylide (6a) while diphenyl sulphide afforded a 12% yield of ylide (6b). Repetition of the reaction with dimethyl sulphide but in the presence of cyclohexene indicated that the sulphide was about six times as reactive as the olefin toward the photochemically generated carbene. These reactions aU were assumed to occur by conversion of the diazo-compound into a singlet carbene, which attacked sulphur. However, it was found that (6a) also could... 

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