Applications of methylsulfonylsulfene in synthesis. Part 1. Conversion of 3,4-dihydro-2H-pyran into cis-2-(C-substituted)tetrahydropyran-3-sulfonates/sulfinates

Abstract

(1R*,6S*,8R*)-8-Methylsulfonyl-2-oxa-7-thiabicyclo[4.2.0]octane 7,7-dioxide 10a, available from the reaction of 3,4-dihydro-2H-pyran and methylsulfonylsulfene 1(generated in situ from MeSO₂Cl and Et₃N), underwent alkylation at position 8 in the presence of sodium hydride and alkyl halides. With methyl iodide and chloromethyl methyl ether, mixtures of the endo- and exo-methyl derivatives 10b and 11b(with 10b in predominance) and the endo- and exo-methoxymethyl derivatives 10c and 11c(with 11c in predominance) were produced. With benzyl chloride, tert-butyl bromoacetate and allyl bromide, only the exo-alkyl derivatives 11d-f were isolated, the stereostructure of compound 11f being established by X-ray crystallography.

In the presence of sodium thiophenoxide and thiophenol, compound 10a underwent a reductive cleavage of its S(7)–C(8) bond to give, after acidification, the sulfinic acid 9a; the sodium salt of the last-cited acid underwent methylation with methyl iodide to give (2S*,3S*)-3-methylsulfonyl-2-(methylsulfonylmethyl)tetrahydropyran 15d. Under corresponding conditions (and also in the presence of a large excess of Na/Hg in MeOH), compound 11f afforded the sulfinic acid 27c which was transformed into (2R*,3S*)-3-methylsulfonyl-2-[(1′R*)-1′-(methylsulfonyl)but-3′-enyl]-tetrahydropyran 21d; the stereostructure of the last cited compound was determined by X-ray crystallography. The sulfinic acid 27c also underwent reaction with diazomethane to give the methyl sulfinate 27b as a ∼ 1 : 1 mixture of diastereoisomers.

In the presence of Raney nickel, compound 10a furnished (2R*)-2-(methylsulfonylmethyl)-tetrahydrofuran 14 whereas compound 11f underwent reduction of its olefinic linkage to give the propyl derivative 11h.

Sodium methoxide in methanol (and also Na/Hg in MeOH) induced an overall hydrolytic cleavage of the S(7)–C(8) bonds of compounds 10a and 11f to give, after acidification, the cis-sulfonic acids 15c and 21b(which were isolated as their methyl esters 15a and 21a). In the presence of sodium hydroxide, the cis-sulfonic acid 15c underwent epimerisation at position 2 to give the trans-sulfonic acid 17c(which was isolated as its methyl ester 17a).