6540
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2. Zanda, M.; Bravo, P.; Volonterio, A. In Asymmetric
nature of the a-substituent R1 are likely to play a key role
Fluoro-Organic Chemistry: Synthesis, Applications, and
Future Directions; Ramachandran, P. V., Ed.; ACS Sym-
posium Series 746; American Chemical Society: Washing-
ton, DC, 1999; pp. 127–141.
in the transition state.
13. Some alkyl halides, such as isobutyl-bromide and 2-bro-
momethyl-dioxolane reacted very sluggishly with a-sub-
stituted sulfoxides 1a,b.
3. Pesenti, C.; Bravo, P.; Corradi, E.; Frigerio, M.; Meille,
S. V.; Panzeri, W.; Viani, F.; Zanda, M. J. Org. Chem.
2001, 66, 5637–5640 and references cited therein.
4. Volonterio, A.; Bravo, P.; Pesenti, C.; Zanda, M. Tetra-
hedron Lett. 2001, 42, 3985–3988.
5. Bravo, P.; Corradi, E.; Pesenti, C.; Vergani, B.; Viani, F.;
Volonterio, A.; Zanda, M. Tetrahedron: Asymmetry 1998,
9, 3731–3735.
6. Bravo, P.; Farina, A.; Kukhar, V. P.; Markovsky, A. L.;
Meille, S. V.; Soloshonok, V. A.; Sorochinsky, A. E.;
Viani, F.; Zanda, M.; Zappala`, C. J. Org. Chem. 1997,
62, 3424–3425.
7. (a) Garc´ıa Ruano, J. L.; Alcudia, A.; del Prado, M.;
Barros, D.; Maestro, M. C.; Ferna´ndez, I. J. Org. Chem.
2000, 65, 2856–2862; (b) Bravo, P.; Capelli, S.; Cru-
cianelli, M.; Guidetti, M.; Markovsky, A. L.; Meille, S.
V.; Soloshonok, V. A.; Sorochinsky, A. E.; Viani, F.;
Zanda, M. Tetrahedron 1999, 55, 3025–3040.
8. To our knowledge the a-C-alkylation of ortho-car-
bamoyl-aryl alkyl sulfoxides has not been reported previ-
ously. For some reviews on the alkylation of metallated
sulfoxides, see: (a) Procter, D. J. J. Chem. Soc., Perkin
Trans. 1 2000, 835–871; (b) Solladie´, G. In Houben-Weyl:
Methods in Organic Synthesis; Mu¨ller, E., Ed.; Thieme:
Stuttgart, 1995; Vol. E21b, pp. 1793–1815; (c) Walker, A.
J. Tetrahedron: Asymmetry 1992, 3, 961–998; (d) Carren˜o,
M. C. Chem. Rev. 1995, 95, 1717–1760.
9. (a) n-BuLi was titrated according to: Kofron, W. G.;
Baclawski, L. M. J. Org. Chem. 1976, 41, 1979–1980.
Using less than 2.6 equiv. of BuLi the reactions were
incomplete; (b) General procedure for the synthesis of
compounds 8a–k. To a cooled solution of 1a (1.83 mmol,
500 mg) and dry HMPA (9.15 mmol, 1.60 mL) in dry
THF (29 mL) was added dropwise, at −70°C and under
an argon atmosphere, a 2.5 M solution of n-BuLi (4.77
mmol, 1.90 mL). After 10 min, at −78°C 3-methyl-1-
bromo-butane (2.01 mmol, 0.252 mL) was added. After
the reaction was complete (TLC monitoring), saturated
aqueous NH4Cl was added, the temperature raised to rt
and the solution extracted with AcOEt. The collected
organic layers were dried over anhydrous Na2SO4,
filtered and the solvent evaporated in vacuo. The residue
was purified by flash-chromatography to give 8a (1.68
mmol, 577 mg) in 92% yield.
14. Xia, M.; Chen, S.; Bates, D. K. J. Org. Chem. 1996, 61,
9289–9292 and references cited therein.
15. (a) Uchida, Y.; Oae, S. Gazz. Chim. Ital. 1987, 117,
649–654 and references cited therein; (b) Walter, W.;
Krische, B. Liebigs Ann. Chem. 1980, 14–27; (c) Cipol-
lina, J. A.; Ruediger, E. H.; New, J. S.; Wire, M. E.;
Shepherd, T. A.; Smith, D. W.; Yevich, J. P. J. Med.
Chem. 1991, 34, 3316–3328; (d) Wright, S. W.; Abelman,
M. M.; Bostrom, L. L.; Corbett, R. L. Tetrahedron Lett.
1992, 33, 153–156; (e) For a highly stereoselective lac-
tonization with displacement of a sulfinyl group under
Pummerer-type conditions, see: Casey, M.; Manage, A.
C.; Murphy, P. J. Tetrahedron Lett. 1992, 33, 965–968.
16. (a) Ancillary experiments showed that, in line with a
carbocationic mechanism, the primary ortho-[(N-
methyl)carbamoyl]phenyl sulfoxide 1e having an electron-
rich R1=4-MeO-C6H4 afforded good yield of
4-MeO-C6H4CH2OH under NOPR conditions, whereas
sulfoxide 1f having R1=4-Me-C6H4 reacted sluggishly
producing low yield of 4-Me-C6H4CH2OH, and 1g with
rather electron-poor R1=4-Br-C6H4 gave no 4-Br-
C6H4CH2OH at all; (b) General procedure for the Pum-
merer reaction. To a cooled solution of 8a (0.23 mmol, 80
mg) and TMP (0.70 mmol, 93 mL) in dry DCM (3 mL)
was added neat TFAA (1.16 mmol, 164 mL) at 0°C and
under an argon atmosphere. The temperature was
allowed to reach rt and the reaction was stirred until
complete disappearance of the starting material (TLC).
The organic solvent was evaporated, the residue diluted
with MeOH and water, then an excess of solid K2CO3
was added until basic pH was reached. The mixture was
extracted with AcOEt, the collected organic layers dried
over anhydrous Na2SO4, filtered, and the solvent evapo-
rated in vacuo. The residue was purified by flash-chro-
matography to give 9a (0.17 mmol, 30 mg) in 73% yield
and 5 (0.20 mmol, 33 mg, 87%); (c) General procedure for
the chloro-Pummerer reaction. To a cooled solution of 8a
(0.24 mmol, 83 mg) and TMP (0.73 mmol, 96 mL) in dry
DCM (3 mL) was added neat oxalyl chloride (0.36 mmol,
32 mL) at −50°C and under an argon atmosphere. After
complete disappearance of the starting material (TLC),
the reaction was quenched with 1N HCl, the temperature
raised to rt and the mixture extracted with DCM. The
collected organic layers were dried on anhydrous
Na2SO4, filtered and the solvent evaporated in vacuo.
The residue was purified by flash-chromatography to give
10b (0.17 mmol, 33 mg) in 71% yield and 5 (0.22 mmol,
36 mg, 92%).
10. No reaction was observed in the following cases: without
HMPA, replacing HMPA with TMEDA, or replacing
BuLi with LDA, except in the case of BnBr which led to
8g with low stereocontrol (see Table 2).
17. Details on these products will be published in a forth-
coming full paper.
11. The crystal structure of 8e will be published in a full
paper.
18. In this case, 1 equiv. of both CO and CO2 are produced,
in analogy with the outcome of the Swern reaction.
12. The dramatic stereoselectivity difference between 1a and
1b suggests that electronic effects depending on the