Job/Unit: O43615
/KAP1
Date: 21-01-15 17:16:32
Pages: 5
J. A. Lujan-Montelongo, A. O. Estevez, F. F. Fleming
FULL PAPER
and dehydration: F. J. A. Hundscheld, V. K. Tandon,
P. H. F. M. Rouwette, A. M. van Leusen, Tetrahedron 1987, 43,
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a) H. Buschmann, C. Puetz, WO 2003068204 A1, 2003; b)
N. C. M. E. Barendse, US 4922016A, 1990.
onto an ice/water mixture, and the resulting mixture was extracted
with EtOAc (4ϫ). The combined organic layers were washed with
brine, and dried (Na2SO4). Some formamides solidified upon cool-
ing, and could be recrystallized from benzene/pentane. All form-
amides were sufficiently pure to be used directly in the dehydration
reaction (after complete removal of volatiles).
[7]
[8]
A round-bottomed flask containing the crude formamide was
purged with N2 (3ϫ), and then a 2:1 mixture of THF/MeCN
(1.5 m) was added to dissolve the formamide. The flask was cooled
to –10 °C, iPr2NH was added dropwise (9.3 equiv.), and POCl3
(3.3 equiv.) was added dropwise at a sufficiently slow rate to keep
the temperature below 5 °C. After 1 h, the mixture was poured onto
a 50:50 mixture of ice/NaHCO3 (satd. aq.). The resulting mixture
was extracted with CH2Cl2 (4ϫ), and the combined organic layers
were washed with brine and dried (Na2SO4). The crude products
were prepurified by passing through a short silica gel plug, eluting
with hexanes/diethyl ether (70:30), and then purified by radial
chromatography. Complete experimental details are provided in the
Supporting Information.
[9]
J. L. García Ruano, A. Parra, F. Yuste, V. M. Mastranzo, Syn-
thesis 2008, 311–312.
G. E. O’Mahony, P. Kelly, S. E. Lawrence, A. R. Maguire, AR-
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The use of formamide alone resulted in a severe increase of
temperature and pressure in the reaction vessel, triggering the
microwave safety sensor to halt further heating.
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[10]
[11]
[12]
[13]
[14]
[15]
Acknowledgments
[16] Although the A value is higher for a phenoxy group than for
a methoxy group, the edge-on steric demand of rotationally
restricted phenyl groups significantly lowers the steric demand:
E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of Or-
ganic Compounds, Wiley, New York, 1994, pp. 597–606 and
particularly p. 698.
Financial support for this research from the NIH (2R15AI051352-
04), CONACYT, and release time from the National Science Foun-
dation (NSF) (IRD) is gratefully acknowledged. The opinions ex-
pressed in this manuscript are those of the authors and do not
necessarily reflect the views of the NSF or the NIH.
[17] For a related mechanism, see: E. Wenschuh, R. Fahsl, R.
Hoehne, Synthesis 1976, 829–830.
[18] Attempts to hydrolyze methyl benzenesulfinate (4a) to the cor-
responding sulfinic acid gave a mixture of sulfinic and sulfonic
acids.
[1] S. Chakrabarty, S. Choudhary, A. Doshi, F.-Q. Liu, R. Mohan,
M. P. Ravindra, D. Shah, X. Yang, F. F. Fleming, Adv. Synth.
Catal. 2014, 356, 2135–2196.
[19] Purification gave sulfone 2o in 40% yield, and formate 8 in
22% yield. Presumably, the lower isolated yield of formate 8 is
due to easy hydrolysis during silica gel chromatography.
[20] Sulfinates derived from benzylic alcohols can ionize and re-
combine to directly form sulfones, but this mechanism appears
to be unlikely, because most of the sulfinates (i.e. 4) do not
contain stabilizing benzylic or allylic substituents: J. Drabow-
icz, B. Bujnicki, P. Biscarini, M. Mikolajczyk, Tetrahedron:
Asymmetry 1999, 10, 3177–3187.
[21] Direct hydrolysis of the sulfinate by adventitious water provides
a conceivable, but unlikely, alternative route to sulfinic acid 10.
Sulfinate hydrolysis would concomitantly release phenyl-
ethanol, but the presence of this compound in the crude reac-
tion mixture could not be definitively excluded. Independently
subjecting phenylethanol to the reaction conditions did cause
esterification to give formate 8 (21% yield), but the reaction
was incomplete, so unreacted phenylethanol should be detected
in the crude reaction mixture if a hydrolysis mechanism was
operating.
[22] For a closely related mechanism, see: H.-H. Li, D.-J. Dong, Y.-
H. Jin, S. K. Tian, J. Org. Chem. 2009, 74, 9501–9504.
[23] A mechanistically distinct cleavage–recombination mechanism
is possible for the conversion of allylic and benzylic sulfinate
esters to sulfones.[22] For selected examples, see: a) I. B. Doug-
lass, B. S. Farah, J. Org. Chem. 1958, 23, 805–807; b) A. C.
Cope, D. E. Morrison, L. Field, J. Am. Chem. Soc. 1950, 72,
59–67; c) ref.[6] and references cited therein.
[2] a) M. Suginome, Y. Ito, Sci. Synth. 2012, 44, 445–531; b) D.
Van Leusen, A. M. Van Leusen, Org. React. 2001, 57, 417–666.
[3] a) R. Manzano, F. Rominger, A. S. K. Hashmi, Organometal-
lics 2013, 32, 2199–2203; b) M. C. Blanco Jaimes, C. R. N.
Böhling, J. M. Serrano-Becerra, A. S. K. Hashmi, Angew.
Chem. Int. Ed. 2013, 52, 7963–7966; Angew. Chem. 2013, 125,
8121–8124; c) A. S. K. Hashmi, Y. Yu, F. Rominger, Organome-
tallics 2012, 31, 895–904; d) A. S. K. Hashmi, D. Riedel, M.
Rudolph, F. Rominger, T. Oeser, Chem. Eur. J. 2012, 18, 3827–
3830; e) A. S. K. Hashmi, C. Lothschütz, K. Graf, T. Häffner,
A. Schuster, F. Rominger, Adv. Synth. Catal. 2011, 353, 1407–
1412; f) A. S. K. Hashmi, C. Lothschütz, C. Böhling, T.
Hengst, C. Hubbert, F. Rominger, Adv. Synth. Catal. 2010, 352,
3001–3012.
[4] For recent examples, see: F. Xiao, H. Chen, H. Xie, S. Chen,
L. Yang, G.-J. Deng, Org. Lett. 2014, 16, 50–53; S. Liang, R.-
Y. Zhang, L.-Y. Xi, S.-Y. Chen, X.-Q. Yu, J. Org. Chem. 2013,
78, 11874–11880; D. H. Ortgies, P. Forgione, Synlett 2013, 24,
1715–1721; N. Umierski, G. Manolikakes, Org. Lett. 2013, 15,
4972–4975; N. Umierski, G. Manolikakes, Org. Lett. 2013, 15,
188–191.
[5] For recent examples, see: H.-S. Li, G. Liu, J. Org. Chem. 2014,
79, 509–516; A. S. Deeming, C. J. Russell, A. J. Hennessy,
M. C. Willis, Org. Lett. 2014, 16, 150–153; X. Lin, G. Wang,
H. Li, Y. Huang, W. He, D. Ye, K.-W. Huang, Y. Yuan, Z.
Weng, Tetrahedron 2013, 69, 2628–2632; R. Chawla, A. K.
Singh, L. D. S. Yadav, Tetrahedron 2013, 69, 1720–1724.
[24] A. M. van Leusen, G. J. M. Boerma, R. B. Helhholdt, H. Sid-
erius, J. Strating, Tetrahedron Lett. 1972, 13, 2367–2368.
Received: December 19, 2014
[6] Sulfonylmethyl isonitriles are typically synthesized by
a
multistep sequence involving sulfinate displacement, oxidation,
4
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