ORGANIC
LETTERS
2008
Vol. 10, No. 5
985-988
Decarboxylative Radical Azidation Using
MPDOC and MMDOC Esters
Erich Nyfeler and Philippe Renaud*
Department of Chemistry and Biochemistry, UniVersity of Berne, Freiestrasse 3,
CH-3012 Berne, Switzerland
Received November 22, 2007
ABSTRACT
An efficient radical-mediated decarboxylative azidation of aliphatic carboxylic acids has been developed. The success of this transformation
hinges on the use of a new type of thiohydroxamate esters (MPDOC esters). These esters are more stable than the classical Barton esters and
less prone to rearrange under radical conditions. In the case of
stable MMDOC esters developed recently by Kim.
r-alkoxy and r-amino acids, optimal results are obtained with the even more
Barton has demonstrated that PTOC (PTOC ) pyridine-2-
thione-N-oxycarbonyl) esters are efficient precursors of alkyl
radicals.1 They have been applied to a wide range of reactions
for the formation of C-H, C-C, and C-X bonds (X, )
heteroatom such as O, N, S, Se, P, etc.).2-4 Despite its
obvious synthetic appeal, the formation of C-N bonds under
decarboxylative conditions remains a formidable task. In an
early attempt to run such a process, diazirines were used as
radical traps by Barton.5 More recently, Porter and Master-
son6 reported the decarboxylative azidation of â-silyl car-
boxylic acids via their PTOC-esters in moderate yield using
ethanesulfonyl azide7 as a radical trap. This transformation
(i.e., converting a carboxylic acid into an azide) is unique
and very attractive due to the versatility of the azide func-
tion.8 However, synthetic applications of the azidation pro-
cedure involving PTOC esters are hampered by the formation
of rearranged products (vide infra). Herein, we present a more
general and efficient method for the decarboxylative azidation
of alkanoic acids via the intermediacy less reactive O-acyl
thiohydroxamates.
The radical azidation of O-adamantane-1-carbamoyl thio-
hydroxamates 1-3 (Scheme 1, eq 1) was chosen as a test
reaction because the 1-adamantyl radical is known to react
efficiently with the benzenesulfonyl azide radical trap.7a The
PTOC ester 1 gave almost exclusively the rearranged
S-pyridyl thioether 5 (Table 1, entry 1). Traces of the azide
4 were detected. This indicates that the PTOC ester 1 is more
reactive than the benzenesulfonyl azide toward the adamantyl
radical. Thus, successful azidation would entail either
(1) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Chem. Commun.
1983, 939.
(2) For reviews, see: (a) Motherwell, W. B.; Imboden, C. Radicals in
Organic Synthesis, Volume 1: Basic Principles; Renaud, P., Sibi, M. P,
Eds.; Wiley-VCH: Weinheim, 2001; p 107. (b) Barton, D. H. R.;
Motherwell, W. B. Heterocycles 1984, 21, 1. (c) Crich, D. Aldrichim. Acta
1987, 20, 35. (d) Barton, D. H. R.; Zard, S. Z. Pure Appl. Chem. 1986, 58,
675. (e) Crich, D.; Quintero, L. Chem. ReV. 1989, 89, 1413. (f) Barton, D.
H. R. Tetrahedron 1992, 48, 2529. (g) Barton, D. H. R. Pure Appl. Chem.
1994, 66, 1943.
(3) (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron Lett.
1983, 24, 4979. (b) Barton, D. H. R.; Lacher, B.; Zard, S. Z. Tetrahedron
Lett. 1985, 26, 5939.
(4) Barton, D. H. R.; Ozbalik, N.; Vacher, B. Tetrahedron 1988, 44,
3501.
(5) Barton, D. H. R.; Jaszberenyi, J. C.; Theodorakis, E. A.; Reibenspies,
J. H. J. Am. Chem. Soc. 1993, 115, 8050.
(6) Masterson, D. S.; Porter, N. A. Org. Lett. 2002, 4, 4253.
(7) (a) Ollivier, C.; Renaud, P. J. Am. Chem. Soc. 2001, 123, 4717. (b)
Ollivier, C.; Renaud, P. J. Am. Chem. Soc. 2000, 122, 6496. For a review
on radical azidation, see: (c) Panchaud, P.; Chabaud, L.; Landais, Y.;
Ollivier, C.; Renaud, P.; Zigmantas, S. Chem. Eur. J. 2004, 10, 3606.
(8) For reviews on preparation and application of azides, see: (a) Bra¨se,
S.; Gil, C.; Kneppner, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005,
44, 5188. (b) Scriven, E. F. V.; Turnbull, K. Chem. ReV. 1988, 88, 297. (c)
L’Abbe´, G. Chem. ReV. 1969, 69, 345.
10.1021/ol702832x CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/14/2008