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X ÿ rr'
R« - benzyl or allyl group
22.214.171.124 Lewis acid-catalysed ketene dithioacetal functionalization
A carbocation obtained from an a-unsaturated orthoester can be added to a ketene dithioacetal as shown .
4.2.2 Thiophilic versus carbophilic addition of organometallics to a C=S bond. Carbanions through thiophilic addition
Many examples of the nucleophilic attack of organometallic compounds at the sulfur atom of thiocarbonyl groups were reported in the 1970s by Beak, Vialle, Ohno, Schaumann and their co-workers [119, 120, 327-329]. This thiophilic addition opens the way for a new method of preparation of carbanions a to sulfur.
If the reaction is carried out on dithioesters. carbanions stabilized by two a-sulfur atoms are formed. Such carbanions are analogous to those obtained by deprotonation of dithioacetals, such as Corey-Seebach
dithiane anions (vide supra Section 2.4), and similar applications can be expected. The reaction of aliphatic Grignard reagents with dithioesters is particularly useful. In THF as the solvent, under controlled temperatures, alkylmagnesium halides (except methylmagnesium halides) were found to give exclusively thiophilic addition. The resulting magnesiodithioacetals could be hydrolysed , alkylated  or condensed with other electrophiles  (R'COR2, CICOOEt. C02, R2NCHO).
S , R3S SMe e© SMe
ì R3MgBr r W W
R'^SMe THF/-17°C tf'^MgBr R’^E
Thiophilic addition of Grignard reagents to methyl dithioates
The reaction was carried out under an N2 atmosphere at a temperature maintained between -20 and — 15°C. The dithioester (lOmmol) was added dropwise to a solution of EtMgBr or i-PrMgBr (30 mmol) in THF. The mixture was stirred until the yellow colour of the dithioester disappeared (—60 min). The solution was quenched by careful addition of aqueous NH,CI (the temperature must be kept under about — 15°C in order to avoid decomposition of the non-hydrolysed magnesiodithioacetals with formation of carbenoid species and coupling reactions). After hydrolysis, the reaction mixture was partitioned between Et20 and brine. The organic layer was washed with brine, dried (MgS04) and concentrated. The dithioacetal was isolated by distillation or flash chromatography.
From  with permission.
Good yields were generally obtained as reported in Table 4.1.
TABLE 4.1 Dithioacetals from dithioesters
R1 R1 Yield of dithioacetal (E = H)
Et Et 76
n-Pr Et 73
n-Bu Et 70
i-Pr° Et 61
“Reaction time 3 h.
Under the same conditions a low yield of dithioacetal was isolated for R1 = t-Bu (23% with R3 = Et). Only dimerization products of carbene intermediates were obtained for R1 = phenyl; however, the corresponding unstable magnesiodithioacetal could be trapped by addition of a good alkylating species before that of the Grignard reagent. An 80% yield of dithioacetal (R1 = Ph, R3 = Et or i-Pr, E = Me) was thus
The thiophilic addition of aliphatic Grignard reagents to dithioesters deserves some comment. Although they are less reactive than organolithium compounds, their reactions are selective. With enethiolizable dithioesters, enethiolization cannot be avoided with the organolithium species, and at low temperatures this can become exclusive . Enethiolization does not interfere in the case of the less
basic Grignard reagents. The useful temperature range to run the reaction is quite narrow. Under about -40°C the reaction with alkanedithioates is often very sluggish and at — 10°C the magnesioanions are not stable. Consequently, methylmagnesium bromide, which is not reactive enough, is not a suitable reagent, and the more convenient is isopropylmagnesium bromide. In some instances trapping of the anions as soon as they are formed can be beneficial. For non-enethiolizable dithioates, organolithium reagents have been shown to be convenient reagents .
The sequence, addition of one equivalent of MeLi to a solution of dithioester (1) and (2) in THF at —78°C, led, after allowing the temperature to rise slowly to 20°C and the usual work up, to dithioacetal (3) in a 79% yield . Dithioacetalization and a Wittig reaction yielded dehydro-ar-curcumene (4).
Br -78°C to 20° Ñ
MeLi (1 eq). THF
The thiophilic addition of Grignard reagents was also carried out with S-allylic and propargylic dithioates. In these cases a [2, 3] sigmatropic rearrangement of the magnesiocarbanion occurred, and alkylation at sulfur yielded the dithioacetals of (3-unsaturated ketones  or of allenic ketones .