Chloromethyl thioethers, synthesis

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

Methylthiomethyl has been used as the protecting group in the total synthesis of neoechinulin A (80TL2817). Cyclo(L-Ala-Gly) was treated with sodium hydride in DMF and N-alkylated with chloromethyl methyl thioether at room temperature, to give the bis(methylthiomethyl) derivative. After further chemical transformations, deprotection was achieved by treatment with methyl iodide in the presence of NaHC03 at 40°C for 3 days, followed by heating in dioxane at 100°C for 1 h. 

The reactions of lithiophosphide reagents with alkyl halides or sulphonate esters have continued to find wide application in the synthesis of new phosphines. A series of phosphino-ethers, e.g., (22), has been prepared from the reactions of chloromethyl-substituted ethers with lithium diphenylphosphide. " A one-step synthesis of macrocyclic phosphino-ethers and -thioethers (23) is afforded by the reactions of dilithio-organophosphides with bis(j8-chloroethyl)-ethers and -thioethers derived from ethane-1,2-diol and ethane-1,2-dithiol, respectively. " A new family of water soluble phosphonio-phosphine ligands (24) has been prepared by the reaction of a,o)-dihaloalkanes with one mole of lithium diphenylphosphide, followed by quatemisation of the intermediate w-haloalkylphosphine with trimethylphosphine. The new ligand system (25) has been prepared by the reaction of chloromethylbenzene-chromium tricarbonyl with... 

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