ORGANIC
LETTERS
2002
Vol. 4, No. 16
2707-2709
A New Tin-Free Source of Amidyl
Radicals
Fabien Gagosz, Cecile Moutrille, and Samir Z. Zard*
Laboratoire de Synthe`se Organique associe´ au CNRS, Ecole Polytechnique,
91128 Palaiseau, France
Received May 21, 2002
ABSTRACT
The readily available N-(O-ethyl thiocarbonylsulfanyl)amides are powerful amidyl radical precursors that undergo 5-exo cyclization to give
pyrrolidinone derivatives via a radical-chain reaction initiated by a small amount of lauroyl peroxide.
Amidyl radicals have been recognized over the past few years
as useful intermediates for the construction of nitrogen-
containing heterocycles.1 Thus, intramolecular cyclization of
an amidyl radical onto an olefin allows the construction of
functionalized pyrrolidinones,2 which can be further elabo-
rated into more complex structures such as alkaloids.3
However, most of the reported methods are based on
stannane technology leading to well-known difficulties of
purification and toxicity. As part of our continuing effort in
this area,4 we wondered if the process based on the addition-
fragmentation to dithiocarbonyl derivatives we extensively
developed for the generation of carbon-centered radicals5
could be applied to amidyl radicals.
For this study, an easy access to N-(O-ethyl thiocarbon-
ylsulfanyl)amides 2 was needed. These hitherto unreported
compounds were eventually readily obtained by a modifica-
tion of a procedure developed by Newcomb and co-workers
for the synthesis of N-phenylthioamides.2e Thus, deprotona-
tion of amide 1 with sodium hydride in refluxing THF
following by inverse addition of the amide salt into a solution
of bis-ethoxythiocarbonyldisulfane in excess furnished the
desired radical precursor 2 as a reasonably stable yellow oil
in yields ranging from 35 to 93% (Scheme 1 and Table 1).
Scheme 1
(1) For recent reviews of the chemistry of nitrogen centered radicals,
see: (a) Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543. (b) Zard,
S. Z. Synlett 1996, 1148-1155. (c) Esker, J. L.; Newcomb, M. AdV.
Heterocycl. Chem. 1993, 58, 1. For a recent review on the synthesis of
heterocycles by radical cyclisation, see: Bowman, W. R.; Bridge, C. F.;
Brookes, P. J. Chem. Soc., Perkin Trans. 1 2000, 1, 1.
(2) For notable examples of amidyl radicals generation and cyclization,
see: (a) Lin, X.; Stien, D.; Weinreb, S. M. Tetrahedron Lett. 2000, 41,
2333. (b) Clark, A. J.; Filik, R. P.; Peacock, J. L.; Thomas, G. H. Synlett
1999, 4, 441. (c) Clark, A. J.; Deeth, R. J.; Samuel, C. J.; Wongtap, H.
Synlett 1999, 4, 444. (d) Esker, J. L.; Newcomb, M. J. Org. Chem. 1994,
59, 2779. (e) Esker, J. L.; Newcomb, M. Tetrahedron Lett. 1993, 34, 6877.
(f) Esker, J. L.; Newcomb, M. J. Org. Chem. 1993, 58, 4933.
(3) We recently completed a short synthesis of (()-γ-lycorane involving
a cascade process starting with a nitrogen-centered radical: Hoang-Cong,
X.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett. 1999, 39, 2125.
(4) (a) Callier-Dublanchet, A.-C.; Quiclet-Sire, B.; Zard, S. Z. Tetrahe-
dron Lett. 1995, 36, 8791. (b) Boivin, J.; Callier-Dublanchet, A.-C.; Quiclet-
Sire, B.; Zard, S. Z. Tetrahedron 1995, 51, 6517. (c) Callier, A.-C.; Quiclet-
Sire, B.; Zard, S. Z. Tetrahedron Lett. 1994, 35, 6109.
We were pleased to find that when a solution of 2a in
refluxing 1,2-dichloroethane was treated with a small amount
of lauroyl peroxide (DLP), a 63% yield of the desired
cyclized product 3a was obtained. The cyclization proceeds
(5) For reviews of our work on xanthates, see: (a) Quiclet-Sire, B.; Zard,
S. Z. Phosphorus, Sulfur, Silicon 1999, 137. (b) Zard, S. Z. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 672.
10.1021/ol026221m CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/04/2002