Novel Burgess reagent mediated C-to-N aryl migration reaction in nitrones

Article abstract of DOI:10.1039/c4ra06835a

Nitrones undergo useful transformations with Burgess reagent. The reaction ostensibly involves a [3 + 2] annulation across a σ-bond followed by rearrangement involving C-to-N aryl migration. On the basis of available experimental evidence, plausible mechanisms for the rearrangement and the overall conversion have been proposed.

Full text of DOI:10.1039/c4ra06835a

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Novel Burgess reagent mediated C-to-N aryl
migration reaction in nitrones†
Cite this: RSC Adv., 2014, 4, 44689
T. S. Sajitha, S. Prathapan and P. A. Unnikrishnan*
Received 9th July 2014
Accepted 5th September 2014
DOI: 10.1039/c4ra06835a
www.rsc.org/advances
Nitrones undergo useful transformations with Burgess reagent. The 1,2,3,5-oxathiadiazolidine intermediates B (Fig. 1) in what may
reaction ostensibly involves a [3 + 2] annulation across a s-bond fol- formally be regarded as a [3 + 2] annulation reaction across a s-
31
lowed by rearrangement involving C-to-N aryl migration. On the basis bond (nitrogen–sulfur bond in this case).
of available experimental evidence, plausible mechanisms for the
With a view to verify [3 + 2] annulation hypothesis and to
exploit its synthetic potential, we examined the reaction of four
rearrangement and the overall conversion have been proposed.
35–38
structurally diverse nitrones
such as N-diphenylmethylene-
N-pheylnitrone (2), N-uorenylidene-N-pheylnitrone (3), (Z)-N-
phenylmethylene-N-phenylnitrone (4a) and (Z)-N-(9-anthra-
cenyl)methylene-N-phenylnitrone (4b) with Burgess reagent
1
,2
Burgess reagent (1) is a versatile reagent in organic synthesis
and its reactivity with a number of nucleophilic functional
3,4
5–8
9,10
11
groups like alcohols, epoxides, 1,2-diols, thiols, oximes
(Fig. 2).
12–26
etc. are well documented. Newer applications
of the reagent
Reaction between N-diphenylmethylene-N-phenylnitrone (2)
as well as several modied forms of the reagent with improved
thermal stability are being reported. Now, chiral versions of
the reagent are also known enabling extensive use in organic
natural product syntheses.
and Burgess reagent (1) was conducted in a 1 : 3 molar ratio in
dry dichloromethane at room temperature. The product
precipitated on adding hexane was identied as methyl
11
26
(diphenylamino)(phenyl)methylenecarbamate (6, Scheme 1). In
Burgess reagent (1) shows unexpected reactivity with N-
oxides and the results are interesting and applicable in
synthesis of several heterocyclic compounds, particularly those
with pharmaceutical applications. A recent report shows an
unexpected N-demethylation of oxymorphone and oxycodone-
N-oxide using Burgess reagent to the corresponding oxazoli-
dines providing a direct synthetic route to naltrexone, naloxone,
a repeat run, careful work up of the reaction mixture under
absolutely moisture free conditions afforded, in addition to 6,
triethylamine–sulphur trioxide complex as colorless needles.
Generation of 6 in the reaction between 2 and Burgess reagent
mandates carbon to nitrogen aryl group migration. This rear-
rangement is reminiscent of a similar C-to-N aryl migration
observed in the chlorosulfonyl isocyanate mediated trans-
24
and other antagonists from oxymorphone. This report
prompted us to investigate the reaction between nitrones and
Burgess reagent. Nitrones being N-substituted 1,3-dipolar
systems undergo [3 + 2] cycloaddition reactions with a variety of
carbon–carbon, carbon–nitrogen, carbon–sulphur, nitrogen–
phosphorus multiple bonded systems to give various heterocy-
39,40
formation of nitrones
and Beckmann rearrangement of
oximes. Though Burgess reagent is known to exhibit myriad
reactivity, this is the rst example for a C-to-N aryl migration
promoted by this versatile reagent. Plausible mechanism for the
27–33
clic systems.
Burgess reagent can be considered as a 1,2-
dipole and hence can participate in a formal [3 + 2] annulation
reaction with elimination of triethylamine with a complimen-
tary 1,3-dipole to yield the corresponding ve-membered
32,34
heterocycle. Nitrones exhibit remarkable nucleophilicity
and hence are expected to react with Burgess reagent to give
Department of Applied Chemistry, Cochin University of Science and Technology,
Cochin 682 022, Kerala, India. E-mail: paunni@gmail.com
†
Electronic supplementary information (ESI) available: See DOI:
0.1039/c4ra06835a
Fig. 1 A Formal [3 + 2] annulation of Burgess reagent across a sigma
bond.
1
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Fig. 2 Nitrones used in the present study of Burgess reagent mediated
C-to-N migration reaction.
Scheme 2
was observed. Carbmate 12 precipitated out on addition of dry
hexane to the reaction mixture. It was separated, puried and
characterized on the basis of spectral and analytical data and
chemical transformations. Hydrolysis of 12 using dil. HCl gave
5-phenylphenanthridin-6(5H)-one (11) in high yields as the only
isolable product.
In continuation, we examined the reaction of (Z)-N-aryl-
methylene-N-phenylnitrones (4a, b) with Burgess reagent. In
this case, the carbamate intermediates 13a, b could not be
isolated and the corresponding diarylamines 7a, b were the only
isolable products (Scheme 3). Though we could not isolate the
carbmate intermediate 13a, b generation of diarylamines 7a, b
is consistent with the C-to-N aryl migration pathway proposed
by us. It may be noted that C-to-N hydrogen migration is an
alternative possibility here. In order to check this possibility, we
carried out careful GC-MS analysis of the reaction mixture. GC-
MS analysis ruled out aniline generation in the reaction of 4a, b
with Burgess reagent and hence the alternative C-to-N hydrogen
migration possibility.
Scheme 1
C-to-N aryl migration reaction is provided in Scheme 1. Struc-
ture of carbamate 6 was further conrmed by chemical trans-
formations. Acid hydrolysis of 6 gave diphenylamine (7) along
with 8 in quantitative yields (Scheme 2).
In order to establish the generality of the novel C-to-N aryl
migration observed by us, we examined the reaction of N-uo-
renylidene-N-pheylnitrone (3) with Burgess reagent. In this case
also, C-to-N aryl migration leading to ring expanded product 12
Scheme 3
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