Transition metal catalyzed ring opening reactions of 2-phenyl-3-vinyl substituted 2H-azirines

Article abstract of DOI:10.1016/j.tetlet.2004.06.046

Treatment of 2-phenyl-3-vinyl-substituted 2H-azirines with Grubbs' catalyst induces a clean rearrangement and affords products derived from carbon-nitrogen bond cleavage of the 2H-azirine ring. However, when the reaction was carried out using Wilkinson's catalyst in an alcoholic solvent, the only product obtained in high yield corresponded to an α,β-unsaturated oxime.

Full text of DOI:10.1016/j.tetlet.2004.06.046

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5991–5993
Transition metal catalyzed ring opening reactions of
2-phenyl-3-vinyl substituted 2H-azirines
Albert Padwa* and Thomas Stengel
Department of Chemistry, Emory University, Atlanta, GA 30322, USA
Received 24 May 2004; accepted 8 June 2004
Available online 26 June 2004
Abstract—Treatment of 2-phenyl-3-vinyl-substituted 2H-azirines with Grubbs’ catalyst induces a clean rearrangement and affords
products derived from carbon–nitrogen bond cleavage of the 2H-azirine ring. However, when the reaction was carried out using
Wilkinson’s catalyst in an alcoholic solvent, the only product obtained in high yield corresponded to an a,b-unsaturated oxime.
Ó 2004 Elsevier Ltd. All rights reserved.
2H-Azirines are highly reactive three-membered unsat-
H
Ph
H
H
+
-
+
hv
urated nitrogen-containing heterocycles that have been
used for the preparation of a wide range of polyfunc-
tional acyclic and cyclic nitrogen-containing com-
pounds.1 This small membered ring can take part in
various chemical transformations since it can act as a
dienophile or as a dipolarophile and can also function as
an electrophile or nucleophile.2 The ring strain
undoubtedly contributes to the high reactivity of the
2H-azirine moiety and makes it an attractive interme-
diate for the preparation of complex heterocyclic ring
systems. The most common method for preparing
2H-azirines involves the photolysis or thermolysis of
vinyl azides.3 This reaction can take place in a concerted
manner or via a vinyl nitrene intermediate.4
N
PhC
N
Ph
R1
H+
H
R1
R1
3
2
N
1
A=B
H
R2OH
R1
OR2
N
Ph
H
R1
C
N
B
Ph
H
A
4
5
Scheme 1.
alkoxyimines 4 and this reaction presumably proceeds
by a pathway involving the intermediate production of
an azaallenium cation (3).8
Earlier work from our laboratory demonstrated that
2H-azirines are photochemically active substrates.5
Upon irradiation into their n–pà absorption bands, the
strained three-membered 2H-azirine ring opens selec-
tively at the C–C bond in a heterolytic fashion resulting
in the formation of a nitrile ylide dipole (2).6 The nitrile
ylide can be trapped by p-bonds to give cycloadducts of
type 5. Due to the pronounced reactivity of nitrile ylides
with various dipolarophiles, 2H-azirines have been
extensively utilized in [3 + 2]-cycloaddition reactions
(Scheme 1).5–7 In the presence of alcohols, the photo-
chemically generated nitrile ylide 2 reacts to form
In recent years there has been considerable interest in
the use of both organometallic reagents and catalysts for
effecting ring cleavage of small ring systems.9 By com-
parison with the extensive studies carried out on the
photochemistry of the 2H-azirine ring system,5–7 its
behavior toward organometallic reagents has been rel-
atively unexplored. In some earlier work, Alper and
Wollowitz10 demonstrated that group VI metal carbo-
nyls [M(CO)6, M@Cr, Mo, W] are useful reagents for
converting 2-aryl 2H-azirines into pyrazines 7. Inter-
estingly, pyrroles such as 8 were obtained in modest
yields when diiron enneacarbonyl was employed as the
organometallic reagent.11 Mechanistic studies indicate
* Corresponding author. Tel.: +1-404-727-0283; fax: +1-404-727-6629;
e-mail: chemap@emory.edu
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.046

5992
A. Padwa, T. Stengel / Tetrahedron Letters 45 (2004) 5991–5993
H
Ph
N
Ar
H
Grubb's
catalyst
H
hv
N
Ar
H
X
Fe2(CO)9
Ar
Ar
Mo(CO)6
N
N
Ph
Ar
N
H
X
Ph
N
X
N
7
8
6
12; X = O
13; X = NPh
14; X = O
15; X = NPh
10; X = O
11; X = NPh
Co2(CO)8
Scheme 3.
R
Ar
N
H
marked contrast to the photochemical behavior of
10 and 11, which afforded 2-phenyloxazole (14) and
1,2-diphenylimidazole (15) as the exclusive products.
The photoproducts are formed by C–C bond fragmen-
tation and subsequent cyclization of the resulting nitrile
ylide. The isolation of isoxazole 12 and pyrazole 13 by
use of the Grubbs’ catalyst clearly indicate that these
transition metal catalyzed transformations occur by C–
N bond fragmentation.
9
Scheme 2.
that the formation of the pyrrole proceeds via carbon–
nitrogen bond cleavage of the 2H-azirine ring. More
surprisingly, treatment of the aryl substituted 2H-azirine
6 with dicobalt octacarbonyl [Co2(CO)8] afforded
2-styrylindoles such as 9 in good–excellent yields
(Scheme 2).12 No mechanistic studies were carried out
and the unusual chemoselectivity encountered as a
function of the organometallic reagent used was not
explained by the authors.10–12
Attention was next turned to the Grubbs’ catalyzed
reaction of methyl (E)-3-phenyl-2H-azirine-2-acrylate
(14). Treatment of 14 in the presence of 5 mol %
Cl2(Cy3P)2Ru@CHPh in CH2Cl2 at 25 °C gave
2-phenyl-5-carbomethoxypyrrole (16) as the exclusive
product in 75% isolated yield. Photolysis of 14, on the
other hand, afforded the isomeric 2-phenyl-3-carbo-
methoxypyrrole (18) in 85% yield (Scheme 4). In an
analogous manner, the reaction of the aldehydic
substituted 2H-azirine 15 with Grubbs’ catalyst fur-
nished the 2,5-disubstituted pyrrole 17 while photolysis
gave the 2,3-disubstituted pyrrole 19 in high yield. The
structures of the disubstituted pyrroles were readily
established by examination of their characteristic NMR
spectra.
In a continuation of our own studies dealing with the
chemical reactivity of 2H-azirines,5 we thought it would
be of interest to further investigate the transition metal
catalyzed reactions of several 2-phenyl-3-vinyl substi-
tuted 2H-azirines. In this letter we report that the
commonly employed Grubbs’ catalyst (first generation)
induces a clean rearrangement, which proceeds via car-
bon–nitrogen bond cleavage of the 2H-azirine ring.
However, when the reaction was carried out using the
popular Wilkinson’s catalyst [Rh(PPh3)3Cl] in an alco-
holic solvent, the only product obtained in high yield
corresponded to an a,b-unsaturated oxime (vide infra).
These results provide further insight into the chemical
behavior of this reactive three-membered heterocyclic
ring with various transition metal catalysts.
Our attempts to carry out a related rearrangement using
Wilkinson’s catalyst [RhCl(PPh3)3] proved to be more
problematic. Exposure of the 2H-azirinyl acrylate 14 to
RhCl(PPh3)3 in CH2Cl2 resulted only in recovered
starting material. When heated at reflux, the reaction
afforded a complex mixture of products, which resisted
separation and purification. However, when 14 was
treated with 5 mol % of Wilkinson’s catalyst in metha-
nol, a clean reaction ensued and the major product
isolated in 65% yield was identified as 5-methoxyimino-
5-phenyl-pent-3-enoic acid methyl ester (22). Similar
results were obtained using ethanol and trifluoroetha-
nol, which furnished the a,b-unsaturated oximes 23
(40%) and 24 (53%). A possible mechanism for the
2H-azirine-RhCl(PPh3)3 reaction involves initial p-
Our first transition metal catalyzed experiments centered
around the use of the ruthenium 4,5-dihydroimidazo-2-
ylidene complex developed by Grubbs and widely
known for its application in organic and polymer syn-
thesis.13 To date, this catalyst is routinely used for ring
closing metathesis (RCM), cross metathesis (CM), and
other metathesis-type reactions. The commercial avail-
ability and effectiveness of the Grubbs’ catalyst now
allow olefin metathesis strategies to be viewed as prac-
tical methods for the synthesis of medium size ring,14
spiro and polycyclic systems15 and natural products.16
A
growing number of newly discovered catalytic processes
mediated by Grubbs’ carbene complex also broaden its
synthetic utility beyond olefin metathesis.17 An investi-
gation of its chemistry with 2H-azirine 10 led to the
discovery that it rapidly induced a rearrangement at
25 °C producing 3-phenylisoxazole (12) in 90% yield.
Reaction of the corresponding N-phenylimine 11 pro-
ceeded similarly and gave 1,3-diphenylpyrazole (13) as
the exclusive product (Scheme 3). These results stand in
R
H
Grubb's
catalyst
hv
H
Ph
Ph
R
N
Ph
N
H
R
N
H
H
16; R = CO2Me
17; R = CHO
18; R = CO2Me
19; R = CHO
14; R = CO2Me
15; R = CHO
Scheme 4.

A. Padwa, T. Stengel / Tetrahedron Letters 45 (2004) 5991–5993
5993
References and notes
H
H
H
Ph
Ph
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MeO2C
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N
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20
14
ROH
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N
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RO
OR
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21
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imino bond (Scheme 5). Ring opening by C–N bond
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Acknowledgements
We gratefully acknowledge support of this work by the
National Science Foundation (CHE-0132651).
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