[18303-04-3]  · C12H17NO4S  · N-(t-Butoxycarbonyl)-p-toluenesulfonamide  · (MW 271.33)

(useful component in Mitsunobu reactions for the direct preparation of protected amines from alcohols)

Physical Data: mp 121-123 °C.

Solubility: sol most common organic solvents.

Form Supplied in: white solid; commercially available.

Preparative Method: the title compound (1) is readily prepared in high yield by addition of t-butanol to tosyl isocyanate.1

Handling, Storage, and Precautions: the reagent can be stored for extended periods of time in an amber bottle at rt.

Mitsunobu Reactions.

Under standard Mitsunobu conditions, primary (eq 1),1 secondary (eq 2),1 and allylic N-Boc sulfonamides (eq 3)4 have been prepared in good yields. The reagent has a pKa of 8.5 in DMSO,2 making it a suitably acidic component in the Mitsunobu3 reaction.

It is possible to selectively remove either of the nitrogen protecting groups of these N-Boc sulfonamides.1 For example, treatment of (2) with Trifluoroacetic Acid, or thermolysis in Dimethyl Sulfoxide affords sulfonamide (3) (eq 4). Alternatively, Sodium Naphthalenide serves to deprotect (2) to give the N-Boc compound (4).

Compound (1) has been effectively used for the formation of the N,N-diprotected ethyl (R)-alaninate (6) from the corresponding (S)-alcohol (5) with clean inversion of stereochemistry (eq 5).5

N-Boc sulfonamide (1) has also proved useful in the synthesis of the thromboxane A2 antagonist (10).6 The Mitsunobu reaction with (1) was carried out on scalemic ester alcohol (7) to provide the desired N-Boc sulfonamide (8) along with diene (9) (eq 6).

A related compound, t-butyl ((2-(trimethylsilyl)ethyl)sulfonyl)carbamate (12), prepared from methanesulfonamide (11) in two steps (eq 7), has also been shown to be an effective component in the Mitsunobu reaction (eq 8) (see also b-Trimethylsilylethanesulfonyl Chloride).7

1. Henry, J. R.; Marcin, L. R.; McIntosh, M. C.; Scola, P. M.; Harris, G. D., Jr.; Weinreb, S. M. TL 1989, 30, 5709.
2. Koppel, I.; Koppel, J.; Degerbeck, F.; Grehn, L.; Ragnarsson, U. JOC 1991, 56, 7172.
3. Mitsunobu, O. S 1981, 1.
4. Yamada, H.; Sodeoka, M.; Shibasaki, M. JOC 1991, 56, 4569.
5. Degerbeck, F.; Fransson, B.; Grehn, L.; Ragnarsson, U. JCS(P1) 1992, 245.
6. Corey, E. J.; Wei-guo, S. TL 1990, 31, 3833.
7. (a) Campbell, J. A.; Hart, D. J. TL 1992, 33, 6247. (b) Campbell, J. A.; Hart, D. J. JOC 1993, 58, 2900.

Steven M. Weinreb & James R. Henry

The Pennsylvania State University, University Park, PA, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.