Polylithiation of thioethers: a versatile route for polyanionic synthons

The successive reaction of phenyl vinyl thioether (1) with n-butyllithium and an electophile [E1=PhCHO, (CH2)4CO, (CH2)5CO] in THF at −78°C gives, after hydrolysis, the expected methylenic hydroxy thioethers (2). Deprotonation of 2 with n-butyllithium followed by a DTBB-catalysed lithiation and reaction with a second electrophile [E2=tBuCHO, PhCHO, Me2CO, (CH2)5CO], at −78°C, gives after hydrolysis the corresponding methylenic diols 3. The same diols can be prepared starting from 1 in a one-pot process without isolation of the hydroxy thioether 2. The same methodology was applied to the cyclopropyl phenyl thioether (4), cyclopropyl 1,3-diols 5 {E1=tBuCHO, PhCHO, [Me(CH2)4]2CO, (CH2)5CO, (CH2)7CO; E2=tBuCHO, Me2CO, (CH2)5CO} being isolated in moderate yields. The successive treatment of bis(phenylthio)methane (7) with: (a) n-butyllithium at 0°C, (b) a carbonyl compound [E1=tBuCHO, Me2CO, Et2CO, (CH2)5CO] at −40°C, (c) lithium and catalytic amount of DTBB (5%) and (d) a second carbonyl compound [E2=iPrCHO, tBuCHO, Me2CO, Et2CO, (CH2)5CO] both at −78°C leads, after hydrolysis, to the expected dihydroxy thioethers 8. When after step (d), a second DTBB-catalysed lithiation is performed at temperatures ranging between −78 and 20°C, the corresponding allylic alcohols 9 were isolated. Finally, treatment of alcohols 9 with a few drops of 6 M hydrochloric acid gives dienes 10 in almost quantitative yields.