The combination of sulfur dioxide and an amine can
lead to the formation of charge transfer complexes; exam-
ples have been known since the early twentieth century,
and during the mid-1900s they received attention from a
structure and bonding perspective.9 Olah has exploited
tertiary amine-SO2 complexes as dehydrating agents.10
However, further applications to organic synthesis have
been very limited.11 Given the known stability of a number
of amine-SO2 complexes we were interested in whether a
simple complex of this type could be exploited as an SO2
equivalent and ideally replace the gaseous reagent in a
Barrett reported the one-pot preparation of sulfonamides
from the combination of aryl Grignard reagents and sulfur
dioxide gas, followed by treatment with sulfuryl chloride
and an appropriate amine.16 The basic process is shown in
Scheme 1. Given the wide occurrence of sulfonamide
functional groups in a range of bioactive compounds this
transformation seemed an ideal candidate to investigate
with an SO2 equivalent.
Scheme 1. One-Pot Preparation of Sulfonamides
number of transformations. The known DABCO (SO2)2
3
complex,12 DABSO, is conveniently prepared in quantita-
tive yield from the direct combination of DABCO and SO2
and is a crystalline bench-stable colorless solid.13 Single
crystal X-ray analysis confirmed the structure was in
agreement with related examples (Figure 1).14
Pleasingly, we found that treatment of a THF suspen-
sion of DABSO with p-tolyl magnesium bromide at
ꢀ40 °C, followed by addition of sulfuryl chloride and then
after warming to room temperature, morpholine, provided
the expected sulfonamide in 67% yield (Table 1, entry 1).
Table 1 documents the scope of the process: Entries 1ꢀ6
demonstrate that variation of the amine component is
readily achieved, including primary, secondary, and allylic
examples. The use of a hydrazine nucleophile was less
successful, with the N-aminomorpholine-derived sulfona-
mide being obtained in only 26% yield (entry 7). As well as
aryl Grignard reagents (entries 8ꢀ10), it was also possible
to employ benzyl (entry 11), allyl (entry 12), alkyl (entry
13), and heteroaryl examples (entry 14). In all cases the
yields of the sulfonamide products were good (50ꢀ80%)
and are comparable with the reactions reported using the
gaseous reagent. The original report includes no examples
of the use of primary amines or of alkenyl or alkyl
Grignard reagents.16
Gaseous SO2 has also been applied to sulfamide pre-
paration: In2006, Rudkevichdemonstratedthattreatment
of anilines with SO2 gas, iodine, and pyridine provided the
corresponding diarylsulfamides.17,18 The authors noted
the need to employ ∼100 equiv of SO2. We found that
DABSO could be used as an effective replacement for
the gaseous reagent in this protocol. For example, N,
N0-diphenylsulfamide was prepared in 63% yield using a
combination of DABSO, aniline, and iodine (Table 2,
entry 1). It should be noted that only 2 equiv of DABSO,
relative to aniline, were employed. Table 2 charts the scope
of the reaction and demonstrates the effective preparation
of a variety of diarylsulfamides.
Figure 1. X-ray crystal structure of DABCO-bis(sulfur dioxide)
adduct, DABSO, with thermal ellipsoids shown at 50% prob-
˚
ability; N...S distances are 2.0958(14) and 2.1732(15) A.
Although we have recently demonstrated the utility of
DABSO in a palladium-catalyzed aminosulfonylation
process15 ꢀ an unprecedented transformation using gas-
eous SO2 ꢀ we wanted to explore DABSO in reactions for
which the use of SO2 has already been established. In 2003,
(9) (a) Divers, E.; Ogawa, M. J. Chem. Soc., Trans. 1900, 77, 327.
Selected examples:(b) Moede, J. A.; Curran, C. J. Am. Chem. Soc. 1949,
71, 852. (c) Hata, T.; Kinumaki Nature 1964, 203, 1378. (d) van der
Helm, D.; Childs, J. D.; Christian, S. D. Chem. Commun. 1969, 887.
(e) Douglas, J. E.; Kollman, P. A. J. Am. Chem. Soc. 1978, 100, 5226.
(f) Wong, M. W.; Wiberg, K. B. J. Am. Chem. Soc. 1992, 114, 7527.
(10) (a) Olah, G. A.; Vankar, Y. D. Synthesis 1978, 702. (b) Olah,
G. A.; Vankar, Y. D.; Gupta, B. G. B. Synthesis 1979, 36. (c) Olah, G. A.;
Vankar, Y. D.; Fung, A. P. Synthesis 1979, 59. (d) Olah, G. A.; Vankar,
Y. D.; Arvanaghi, M. Synthesis 1979, 984. (e) Olah, G. A.; Arvanaghi,
M.; Vankar, Y. D. Synthesis 1980, 660.
ꢀ
(11) Eugene, F.; Langlois, B.; Laurent, E. J. Org. Chem. 1994, 59,
2599.
(12) Santos, P. S.; Mello, M. T. S. J. Mol. Struct. 1988, 178, 121.
(13) For DABCO-AlMe3 (DABAL) used as a stable version of
AlMe3, see: Biswas, K.; Prieto, O.; Goldsmith, P. J.; Woodward, S.
Angew. Chem., Int. Ed. 2005, 4, 2232.
(14) Low temperature, single crystal diffraction data were collected
on using a Nonius Kappa CCD diffractometer; data were reduced using
DENZO-SMN/SCALEPACK [Otwinowski, Z.; Minor, W. Methods
Enzymol. 1997, 276, 307], solved using SIR92 [Altomare, A.; Cascarano,
G.; Giacovazzo, C.; Guagliardi, A. J. Appl. Crystallogr. 1994, 27, 435]
and refined within the CRYSTALS suite [Betteridge, P. W.; Carruthers,
J. R.; Cooper, R. I.; Prout, K.; Watkin, D. J. J. Appl. Crystallogr. 2003,
36, 1487. Cooper, R. I.; Thompson, A. L.; Watkin, D. J. J. Appl.
Crystallogr. 2010, 43, 1100]. Full refinement details are given in the
Supporting Information (CIF); Crystallographic data (excluding struc-
ture factors) have been deposited with the Cambridge Crystallographic
ac.uk/data_request/cif.
(16) Pandya, R.; Murashima, T.; Tedeschi, L.; Barrett, A. G. M. J.
Org. Chem. 2003, 68, 8274.
(17) Leontiev, A. V.; Rasika Dias, H. V.; Rudkevich, D. M. Chem.
Commun. 2006, 2887.
(15) Nguyen, B.; Emmett, E. J.; Willis, M. C. J. Am. Chem. Soc. 2010,
132, 16372.
(18) The authors noted that SO2 in combination with NEt3 in MeCN
was also an effective reagent combination.
Org. Lett., Vol. 13, No. 18, 2011
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