6496
J. Am. Chem. Soc. 2000, 122, 6496-6497
Formation of Carbon-Nitrogen Bonds via a Novel
Radical Azidation Process
Scheme 1
Cyril Ollivier and Philippe Renaud*
UniVersit e´ de Fribourg, Institut de Chimie Organique
P e´ rolles, CH-1700 Fribourg, Switzerland
ReceiVed February 24, 2000
Radical reactions are nowadays a very useful tool for organic
synthesis as demonstrated by their frequent application in the
1
preparation of natural products. The majority of these processes
are based on very efficient formation of carbon-hydrogen and
carbon-carbon bond. The formation of a carbon-heteroatom
bond from a carbon-centered radical is also well-documented
2
when the heteroatom is sulfur, halogen, and oxygen. The amina-
tion of alkyl radicals was investigated, too, and even though many
different radical traps were tested, the preparative procedures that
arose from this work are of limited scope. In this contribution,
we report preliminary results concerning a novel and unique
azidation process of simple alkyl iodides and dithiocarbonates
based on the use of ethanesulfonylazide as radical trap.
Ethanesulfonylazide, easily prepared from ethanesulfonyl-
choride and sodium azide, is a stable liquid that can be heated at
The reaction was tested first with different alkyl iodides
equation 1) and results are summarized in Table 1. Cyclic
3
(
secondary alkyl iodides such as 1a and 1b are efficiently converted
into the corresponding azides 2a and 2b by treatment with 3 equiv
9
of ethanesulfonylazide and a substoichiometric amount of DLP
in a mixture of chorobenzene and heptane as solvent (method A,
entries 1 and 2). Sterically more hindered secondary cyclic iodides
such as 1c and 1d are efficiently converted into azides 2c and 2d
by treatment with 5 equiv of ethanesulfonylazide (method B,
entries 3 and 4). Tertiary alkyl iodides such as 1e are also suitable
substrates for this azidation reaction (entry 5), in this case, total
conversion is achieved with 0.35 equiv of DLP (87% yield
100 °C without decomposition. Our hypothesis was that addition
of alkyl radicals in the R or γ position of ethanesulfonylazide
should lead to intermediate nitrogen-centered radicals (I or II).
These radicals should fragment to give alkyl azides and the
ethanesulfonyl radical that decomposes readily to give sulfur
dioxide and the ethyl radical (Scheme 1).4 Since the ethyl radical
is known to be an efficient promoter of iodine atom and dithio-
carbonate transfer reactions, this reaction sequence is expected
to be suitable for radical azidation of iodides and dithiocarbon-
,5
1
according to H NMR, 77% isolated yield). As expected, primary
alkyl iodides gave only low yields as demonstrated by the
conversion of 1f to 2f (entry 6). Indeed, with this substrate, the
iodine transfer between the ethyl radical and the primary iodide
is nearly thermoneutral; therefore, the chain reaction cannot be
very efficient. Iodides resulting from an iodolactonization process
are of synthetic interest; however, the presence of a â-acyloxy
6
ates. Dilauroyl peroxide (DLP) has already proved to be an
excellent initiator for the transfer of iodine atoms and dithiocar-
bonates.7 Therefore, it should also be efficient for the azidation
reaction.
,8
10
group slows the reaction, under optimized conditions (method
B) yields of 60 and 56% have been reached (entries 7 and 8).
When method A was used with these substrates, formation of
reduction product (X ) H) was observed, presumably occurring
by hydrogen atom abstraction from heptane. For substrate 1h, it
is of interest to mention that the classical ionic substitution
reaction with sodium azide failed to give the corresponding azide
(
1) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. ReV. 1991, 91, 1237.
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(
Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: Oxford,
988. Curran, D. P. In ComprehensiVe Organic Synthesis; Trost, B. M.,
1
Fleming I., Eds.; Pergamon: Oxford, 1991; Vol. 4, p 715. Motherwell, W.
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11
2h.
1
999; p 501.
3) Several reagents have been tested for radical amination. Nitric oxide:
(
(4) During their study of Curtius-type rearrangement based on thermal
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3
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(8) Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 672.
(9) The use of 1 equiv of DLP was in some cases necessary to reach 100%
conversion; however, in most cases good conversions were observed with
less than 0.5 equiv of DLP.
5
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7
R.; Lucarini, M.; Nanni, A.; Nanni, D.; Pedulli, F. G.; Tundo, A.; Zanardi, G.
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8
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1
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1
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0.1021/ja000673h CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/24/2000