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Generation, cycloadditions, and tautomerism of n-acyl munchnones
Tetrahedron Letters,Vol.29,No.l7,pp Printed in Great Britain
2027-2030,1988
0040-4039/88 $3.00 + .OO Pergamon Press plc
GENERATION, CYCLOADDITIONS, AND TAUTOMERISM OF N-AWL MUNCHNONES Richard
G. Wilde*1
Contribution from the S. M. McElvain Laboratory of Organic Chemistry, Department of Chemistry, University of Wisconsin, Madison, WI 53706 N-acyl Abstract: acylationldesilylation equilibrated
munchnones reaction of
through
ring-chain
were generated 5-siloxyoxazoles.
valence
for
tautomerism
the first time by These munchnones
and
afforded
two
a novel partially
cycloadducts
with DMAD. In the course of our studies in the 1,3-dipolar cycloadditions of thioaldehydes.2 we briefly investigated N-acyl “munchnones” (l),a class of stabilized azomethine ylides that had yet to be reported in the literature.3 Past experience in this laboratory with azomethine ylides4 and related findings in generation of 1,3-dipoles in general5 suggested a silicon-mediated approach. We wish to report our findings in this area. 5-Siloxyoxazoles (2) were prepared according to the procedure of Takei et al.6 Methylene chloride solutions of 2 were treated with various acid halides at -780C. Upon
slow
warming
concomitant were
to OoC,
desilylation
trapped
with cycloadducts
fair
yields
to good
stable the
and
(Scheme
fluoride, and were obtained
easier
sequence
mediated dimethyl
intermediate than benzoyl Better yields
is
the
to handle probably
oxazoles by
the
were halide
acylated counterion.
acetylenedicarboxylate
extruded I).7
at
nitrogen The
dioxide
to
Benzoyl
chloride
gave
afford yields
N-acyl
the
important;
analogous acylation
trimethylsiloxy preceeds
munchnones and
pyrroles
the
(3) in
if not better,
generally cleaner. which were more
compounds.
desilylation
underwent
in situ,
as good,
the reactions using the chloride were with the t-butyldimethylsiloxy oxazoles, than
N-acyl
(DMAD)
carbon
and
to
Timing generate
of the
1,3-dipoles. Results of the experiment employing non-acetylenic dipolarophiles (such as N-acyl thiocarbonyl compounds or N-phenyl maleimide) were not promising. cycloaddition. It munchnones appear to be relatively unreactive 1,3-dipoles for stands to reason that replacing an alkyl group on the nitrogen with an acyl group will
2027
2028
Scheme
I
R
DMAD
Scheme II
G
11
B
R’
R
Ph Ph Me Me Me Me H
H H H H Me Me Me
Me3 Me3 tBuMe2 tBuMe2 tBuMe2 tBuMe2 tBuMe2
X
Y&l&J
a
Ph Ph Me Et0 Me EiO Et0
13 13 45 51 77 55 67
F
a Cl Cl Cl Q
la
It
-
I
0 0
H H H H Me
DMAD
lb
-co2 R
”
1”’GX3 Ph Ph Me Me H
Me3 tBuMe2 tBuMc2 tBuMe2 tBuMe2
Me Me Ph Ph Me
a a
a F a
10 39 36 9 56
5 7 9 1 5
2029
lower the electron density over the azallyl system. The MO energies will be lower, and the HOMO(dipole)-LUMO(dipolarophile) gap will increase. The reason why DMAD was a successful trapping agent could be that a reversible addition step was driven by loss Doubly-bonded dipolarophiles do not enjoy this of CO2 to give the aromatic pyrrole. advantage. A second piece of evidence for unusual dipole reactivity was the isolation of two pyrrole products from reactions employing substrates where the substituents on the oxazole and the acylating agent were not the same (ie. R # G; Scheme II). Apparently, the N-acyl munchnone intermediate was equilibrating through ring-chain valence tautomerism. Behavior of this sort has been observed earlier for N-alkyl munchnones by Huisgen et al.8 They reported trapping the amidoketene intermediate with certain imines in [2+2] cycloadditions at 1OOoC. In our reactions, the tautomerism was evident The at lower temperatures, probably due to the presence of the extra acyl group. product ratios from the reactions employing phenyl-substituted oxazole + acetyl The chloride and methyl-substituted oxazole + benzoyl halides were not the same. equilibrium of isomeric N-acyl munchnones was slow in relation to the rates of We did not detect trapping and subsequent CO2 loss, which was irreversible. isomerization product (1 b) in the cases where ethyl chloroformate was used as the acylating agent (G = OEt). Presumably, the equilibria heavily favor the product with carbamate functionality over that with ethoxy substitution on the ring. The Other activation schemes employing siloxyoxazoles were investigated. oxazoles 2 could be N-alkylated with methyl triflate, and cesium fluoride desilylation generated the “normal”-type munchnones (Scheme III), which were trapped in situ with DMAD and thiobenzophenone. Reaction of the oxazoles with other activating reagents, such as trimethylsilyl chloride or toluenesulfonic chloride, gave small yields of cycloadducts with DMAD. Scheme III
2. CsF 11%
2030
Thus, a novel route to N-acyl munchnones by acylation/desilylation was investigated. The sequence was somewhat analogous to the method of Achiwa5a for generation of acyclic N-acyl azomethine ylides. The munchnones exhibited a ringchain valence tautomerism and gave two different pyrrole cycloadducts with acetylenic dipolarophiles. They were unreactive toward doubly-bonded dipolarophiles. Acknowledgements:
discussion
RGW thanks Prof. Edwin Vedejs for guidance during the preparation of this manuscript.
and helpful
References:
1) NIH PHS Postdoctoral Fellow, 1987-89. Current address: Roger Adams Labs, School of Chemical Sciences, University of Illinois-Urbana-Champaign, 1209 W. California St., Urbana, IL 61801. 2) Vedejs, E.; Wilde, R. G. J. Org. Chem. 1986, 51, 117. 3) For a review on N-alkyl munchnones, consult: Potts, K. T. 1,3-D ipolar Cycloaddition Chemistry, A. Padwa, ed.; Chapter 8; John Wiley, Inc.: New York, 1984. 4) (a) Vedejs, E.; Larsen, S.; West, F. G. J. Org. Chem. 1985, 50, 2170. (b) Review: Vedejs, E.; West, F. G. Chem. Rev. 1986, 86, 941. 5) (a) Achiwa, K.; Sekiya, M. Heterocycles 1983, 20, 167. (b) Cunico, R. F.; Bedell, L. J. Org. Chem. 1983,48, 2780. (c) Robl, J. A.; Hwu, J. R. J. Org. Chem. 1985, 50, 5913. (d) Padwa, A.; Koehler, K. F. J. Chem. Sot., Chem. Commun. 1986, 789. 6) Takagaki, H.; Yasuda, N.; Anoka, M.; Takei, H. Chem. Lett. 1979, 183. 7) The products were characterized to our satisfaction on the basis of NMR, IR, and mass spectra. 8) (a) Huisgen, R.; Funke, E.; Schaefer, F. C.; Knot-r, R. Angew. Chem., Znt. Ed. Engl. 1967, 6, 367. (b) Bayer, H. 0.; Huisgen, R.; Knorr, R.; Schaefer, F. C. Chem. Ber. 1970, ZO3, 2581. (c) Funke, E.; Huisgen, R. Ibid. 1971, 104, 3222.
(Received
in USA 9 December 1987)
2027-2030,1988
0040-4039/88 $3.00 + .OO Pergamon Press plc
GENERATION, CYCLOADDITIONS, AND TAUTOMERISM OF N-AWL MUNCHNONES Richard
G. Wilde*1
Contribution from the S. M. McElvain Laboratory of Organic Chemistry, Department of Chemistry, University of Wisconsin, Madison, WI 53706 N-acyl Abstract: acylationldesilylation equilibrated
munchnones reaction of
through
ring-chain
were generated 5-siloxyoxazoles.
valence
for
tautomerism
the first time by These munchnones
and
afforded
two
a novel partially
cycloadducts
with DMAD. In the course of our studies in the 1,3-dipolar cycloadditions of thioaldehydes.2 we briefly investigated N-acyl “munchnones” (l),a class of stabilized azomethine ylides that had yet to be reported in the literature.3 Past experience in this laboratory with azomethine ylides4 and related findings in generation of 1,3-dipoles in general5 suggested a silicon-mediated approach. We wish to report our findings in this area. 5-Siloxyoxazoles (2) were prepared according to the procedure of Takei et al.6 Methylene chloride solutions of 2 were treated with various acid halides at -780C. Upon
slow
warming
concomitant were
to OoC,
desilylation
trapped
with cycloadducts
fair
yields
to good
stable the
and
(Scheme
fluoride, and were obtained
easier
sequence
mediated dimethyl
intermediate than benzoyl Better yields
is
the
to handle probably
oxazoles by
the
were halide
acylated counterion.
acetylenedicarboxylate
extruded I).7
at
nitrogen The
dioxide
to
Benzoyl
chloride
gave
afford yields
N-acyl
the
important;
analogous acylation
trimethylsiloxy preceeds
munchnones and
pyrroles
the
(3) in
if not better,
generally cleaner. which were more
compounds.
desilylation
underwent
in situ,
as good,
the reactions using the chloride were with the t-butyldimethylsiloxy oxazoles, than
N-acyl
(DMAD)
carbon
and
to
Timing generate
of the
1,3-dipoles. Results of the experiment employing non-acetylenic dipolarophiles (such as N-acyl thiocarbonyl compounds or N-phenyl maleimide) were not promising. cycloaddition. It munchnones appear to be relatively unreactive 1,3-dipoles for stands to reason that replacing an alkyl group on the nitrogen with an acyl group will
2027
2028
Scheme
I
R
DMAD
Scheme II
G
11
B
R’
R
Ph Ph Me Me Me Me H
H H H H Me Me Me
Me3 Me3 tBuMe2 tBuMe2 tBuMe2 tBuMe2 tBuMe2
X
Y&l&J
a
Ph Ph Me Et0 Me EiO Et0
13 13 45 51 77 55 67
F
a Cl Cl Cl Q
la
It
-
I
0 0
H H H H Me
DMAD
lb
-co2 R
”
1”’GX3 Ph Ph Me Me H
Me3 tBuMe2 tBuMc2 tBuMe2 tBuMe2
Me Me Ph Ph Me
a a
a F a
10 39 36 9 56
5 7 9 1 5
2029
lower the electron density over the azallyl system. The MO energies will be lower, and the HOMO(dipole)-LUMO(dipolarophile) gap will increase. The reason why DMAD was a successful trapping agent could be that a reversible addition step was driven by loss Doubly-bonded dipolarophiles do not enjoy this of CO2 to give the aromatic pyrrole. advantage. A second piece of evidence for unusual dipole reactivity was the isolation of two pyrrole products from reactions employing substrates where the substituents on the oxazole and the acylating agent were not the same (ie. R # G; Scheme II). Apparently, the N-acyl munchnone intermediate was equilibrating through ring-chain valence tautomerism. Behavior of this sort has been observed earlier for N-alkyl munchnones by Huisgen et al.8 They reported trapping the amidoketene intermediate with certain imines in [2+2] cycloadditions at 1OOoC. In our reactions, the tautomerism was evident The at lower temperatures, probably due to the presence of the extra acyl group. product ratios from the reactions employing phenyl-substituted oxazole + acetyl The chloride and methyl-substituted oxazole + benzoyl halides were not the same. equilibrium of isomeric N-acyl munchnones was slow in relation to the rates of We did not detect trapping and subsequent CO2 loss, which was irreversible. isomerization product (1 b) in the cases where ethyl chloroformate was used as the acylating agent (G = OEt). Presumably, the equilibria heavily favor the product with carbamate functionality over that with ethoxy substitution on the ring. The Other activation schemes employing siloxyoxazoles were investigated. oxazoles 2 could be N-alkylated with methyl triflate, and cesium fluoride desilylation generated the “normal”-type munchnones (Scheme III), which were trapped in situ with DMAD and thiobenzophenone. Reaction of the oxazoles with other activating reagents, such as trimethylsilyl chloride or toluenesulfonic chloride, gave small yields of cycloadducts with DMAD. Scheme III
2. CsF 11%
2030
Thus, a novel route to N-acyl munchnones by acylation/desilylation was investigated. The sequence was somewhat analogous to the method of Achiwa5a for generation of acyclic N-acyl azomethine ylides. The munchnones exhibited a ringchain valence tautomerism and gave two different pyrrole cycloadducts with acetylenic dipolarophiles. They were unreactive toward doubly-bonded dipolarophiles. Acknowledgements:
discussion
RGW thanks Prof. Edwin Vedejs for guidance during the preparation of this manuscript.
and helpful
References:
1) NIH PHS Postdoctoral Fellow, 1987-89. Current address: Roger Adams Labs, School of Chemical Sciences, University of Illinois-Urbana-Champaign, 1209 W. California St., Urbana, IL 61801. 2) Vedejs, E.; Wilde, R. G. J. Org. Chem. 1986, 51, 117. 3) For a review on N-alkyl munchnones, consult: Potts, K. T. 1,3-D ipolar Cycloaddition Chemistry, A. Padwa, ed.; Chapter 8; John Wiley, Inc.: New York, 1984. 4) (a) Vedejs, E.; Larsen, S.; West, F. G. J. Org. Chem. 1985, 50, 2170. (b) Review: Vedejs, E.; West, F. G. Chem. Rev. 1986, 86, 941. 5) (a) Achiwa, K.; Sekiya, M. Heterocycles 1983, 20, 167. (b) Cunico, R. F.; Bedell, L. J. Org. Chem. 1983,48, 2780. (c) Robl, J. A.; Hwu, J. R. J. Org. Chem. 1985, 50, 5913. (d) Padwa, A.; Koehler, K. F. J. Chem. Sot., Chem. Commun. 1986, 789. 6) Takagaki, H.; Yasuda, N.; Anoka, M.; Takei, H. Chem. Lett. 1979, 183. 7) The products were characterized to our satisfaction on the basis of NMR, IR, and mass spectra. 8) (a) Huisgen, R.; Funke, E.; Schaefer, F. C.; Knot-r, R. Angew. Chem., Znt. Ed. Engl. 1967, 6, 367. (b) Bayer, H. 0.; Huisgen, R.; Knorr, R.; Schaefer, F. C. Chem. Ber. 1970, ZO3, 2581. (c) Funke, E.; Huisgen, R. Ibid. 1971, 104, 3222.
(Received
in USA 9 December 1987)