COMMUNICATIONS
Table 5. Deprotection of cyclic sulfamides to yield nonsymmetrical,
monosubstituted sulfamides.
(30 mL). The aqueous phase was re-extracted with CH
2 2
Cl (2 î 20 mL) and
the combined organic phase was dried (Na SO ), filtered, and concen-
2
4
O
O
trated. Flash column chromatography on silica gel then provided the
desired products in the yields quoted.[
O
N
O
18]
R1
S
CO2Y
R1
S
N
N
Conditions
NH
Received: July 1, 2002 [Z19644]
R2
R3
R2
R3
Entry Starting material (Yield [%])[a] Product
Yield [%]
[
1] For a small sampling of this extensive literature, see: a) R. J. Cherney,
B. W. King, WO-2002028846 2002 [Chem. Abst. 2002, 136, 309923];
b) N.-Y. Shih, H.-J. Shue, G. A. Reichard, S. Paliwal, D. J. Blythin, J. J.
Piwinski, D. Xiao, X. Chen, WO-2001044200 2001 [Chem. Abst. 2001,
99[b]
1
1
2
35, 61331]; c) G. M. Benson, M. C. Rutledge, K. L. Widdowson, WO-
000076501 2000 [Chem. Abst. 2001, 134, 56675]; d) R. D. Tung, F. G.
Salituro, D. D. Deininger, G. R. Bhisetti, C. T. Baker, A. Spaltenstein,
US-5945413 1999 [Chem. Abst. 1999, 131, 185247]; e) I. Mcdonald,
D. J. Dunstone, M. J. Tozer, WO-9905141 1999 [Chem. Abst. 1999, 130,
99[b]
2
3
4
5
1
68372].
[
2] a) W. Schaal, A. Karlsson, G. Ahlsÿn, J. Lindberg, H. O. Andersson,
U. H. Danielson, B. Classon, T. Unge, B. Samuelsson, J. Hultÿn, A.
Hallberg, A. Karlÿn, J. Med. Chem. 2001, 44, 155 ± 169; b) A.
Spaltenstein, M. R. Almond, W. J. Bock, D. Cleary, E. S. Furfine,
R. J. Hazen, W. M. Kazmierski, F. G. Salituro, R. D. Tung, L. L.
Wright, Bioorg. Med. Chem. Lett. 2000, 10, 1159 ± 1162; c) K. B‰ckbro,
S. Lˆwgren, K. ÷sterlund, J. Atepo, T. Unge, J. Hultÿn, N. M.
Bonham, W. Schaal, A. Karlÿn, A. Hallberg, J. Med. Chem. 1997, 40,
97[c]
98[c]
84[d]
87[d]
8
98 ± 902; d) J. Hultÿn, N. M. Bonham, U. Nillroth, T. Hansson, G.
Zuccarello, A. Bouzide, J. Aqvist, B. Classon, U. H. Danielson, A.
Karlÿn, I. Kvarnstrom, B. Samuelsson, A. Hallberg, J. Med. Chem.
1
997, 40, 885 ± 897.
[
3] a) R. Kuang, J. B. Epp, S. Ruan, L. S. Chong, R. Venkataraman, J. Tu,
S. He, T. M. Truong, W. C. Groutas, Bioorg. Med. Chem. 2000, 8,
1
005 ± 1016; b) R. Kuang, J. B. Epp, S. Ruan, H. Yu, P. Huang, S. He, J.
6
Tu, N. M. Schechter, J. Turbov, C. J. Froelich, W. C. Groutas, J. Am.
Chem. Soc. 1999, 121, 8128 ± 8129; c) W. C. Groutas, N. M. Schechter,
S. He, H. Yu, P. Huang, J. Tu, Bioorg. Med. Chem. Lett. 1999, 9, 2199 ±
[
[
a] Yield in parentheses is that for synthesis of the starting material.
b] NaOH, MeOH:H O (2:1), 258C, 2 h. [c] Pd(OAc) (10 mol%), 3,3’,3’’-
2
204; d) W. C. Groutas, R. Kuang, S. Ruan, J. B. Epp, R. Venkatara-
2
2
man, T. M. Truong, Bioorg. Med. Chem. 1998, 6, 661 ± 671.
phosphinidynetris(benzenesulfonic acid) trisodium salt (20 mol%), HNEt
40 equiv), MeCN:H O (1:1), 258C, 15 min. [d] 10% Pd/C, H , EtOH:
EtOAc (4:1), 258C, 2 h.
2
[
4] J. L. Castro, R. Baker, A. R. Guiblin, S. C. Hobbs, M. R. Jenkins,
M. G. N. Russell, M. S. Beer, J. A. Stanton, K. Scholey, R. J. Har-
greaves, M. I. Graham, V. G. Matassa, J. Med. Chem. 1994, 37, 3023 ±
(
2
2
3
032.
[
5] M. J. Tozer, I. M. Buck, T. Cooke, S. B. Kalindjian, I. M. McDonald,
M. J. Pether, K. I. M. Steel, Bioorg. Med. Chem. Lett. 1999, 9, 3103 ±
thesis of compounds represented by structure IV (Scheme 1)
has been realized.
3
108.
In conclusion, we have developed a practical and high-
yielding method for the efficient, one-stepsynthesis of diverse
classes of N,N’-differentiated sulfamides from a wide range of
amino alcohols and simple amines using Burgess-type re-
agents. This synthetic technology constitutes a marked
improvement over those currently in the literature, and
should extend the potential applications of sulfamides not
only within chemical biology and medicinal chemistry, but
also in the fields of asymmetric synthesis and supramolecular
chemistry. At a more fundamental level, this methodology, in
conjunction with additional applications currently under
development in these laboratories, serves to delineate new
pathways in which the power of the Burgess reagent and its
relatives can be applied to effect transformations of critical
importance in chemical synthesis.
[
6] a) S. V. Pansare, A. N. Rai, S. N. Kate, Synlett 1998, 623 ± 624; b) K. H.
Ahn, D. J. Yoo, J. S. Kim, Tetrahedron Lett. 1992, 33, 6661 ± 6664; c) D.
Sartor, J. Saffrich, G. Helmchen, C. J. Richards, H. Lambert,
Tetrahedron: Asymmetry 1991, 2, 639 ± 642. The use of sulfamides as
chiral auxiliaries was inspired by their close structural homology to
Oppolzer©s family of highly versatile chiral sultams which are
chartered in the following papers: a) W. Oppolzer, A. J. Kingma,
S. K. Pillai, Tetrahedron Lett. 1991, 32, 4893 ± 4896; b) W. Oppolzer, C.
Starkemann, I. Rodriguez, G. Bernardinelli, Tetrahedron Lett. 1991,
3
2, 61 ± 64.
7] a) F. Hof, P. M. Iovine, D. W. Johnson, J. Rebek, Jr. Org. Lett. 2001, 3,
247 ± 4249; b) F. Hof, C. Nuckolls, S. L. Craig, T. MartÌn, J. Rebek, Jr.
[
4
J. Am. Chem. Soc. 2000, 122, 10991 ± 10996; c) B. Gong, C. Zheng, H.
Zeng, J. Zhu, J. Am. Chem. Soc. 1999, 121, 9766 ± 9767, and references
in each.
8] a) M. Preiss, Chem. Ber. 1978, 111, 1915 ± 1921; b) S. H. Rosenberg,
J. F. Dellaria, D. J. Kempf, C. W. Hutchins, K. W. Woods, R. G. Maki,
E. de Lara, K. P. Spina, H. H. Stein, J. Cohen, W. R. Baker, J. J.
Plattner, H. D. Kleinert, T. J. Perun, J. Med. Chem. 1990, 33, 1582 ±
[
1
3
590; c) G. Dewynter, N. Aouf, J.-L. Montero, Tetrahedron Lett. 1991,
2, 6545 ± 6548.
Experimental Section
Representative procedure: The desired Burgess reagent (1±3, 1.25 mmol,
[9] An online search of the available chemicals directory revealed just
slightly more than 200 unsubstituted 1,2-diamine substrates. By
contrast, there are over 3000 unsubstituted b-amino alcohols.
[10] See Ref. [5a] and a) J. M. Dougherty, D. A. Probst, R. E. Robinson,
J. D. Moore, T. A. Klein, K. A. Snelgrove, P. R. Hanson, Tetrahedron
2
.5 equiv) was added in one portion to a stirred solution of amino alcohol
0.5 mmol, 1.0 equiv) in THF (2 mL). The reaction mixture was then
subjected to the conditions defined in the Tables. Upon completion, the
reaction was diluted with CH Cl (20 mL) and washed with 1n HCl
(
2
2
Angew. Chem. Int. Ed. 2002, 41, No. 20
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/4120-3869 $ 20.00+.50/0
3869