An approach toward oxidopyrylium ylides using Rh(II)-catalyzed cyclization chemistry

Article abstract of DOI:10.1016/j.tetlet.2007.06.118

The Rh(II)-catalyzed reaction of the E-isomer of 2-diazo-3,6-dioxo-6-phenyl-hex-enoic acid methyl ester was carried out in the presence of various carbonyl compounds and was found to give 1,3-dioxoles in moderate to good yield. In an attempt to prepare th

Full text of DOI:10.1016/j.tetlet.2007.06.118

Tetrahedron Letters 48 (2007) 5938–5941
An approach toward oxidopyrylium ylides using
Rh(II)-catalyzed cyclization chemistry
Albert Padwa,a,* Jutatip Boonsombata and Paitoon Rashatasakhonb,*
aDepartment of Chemistry, Emory University, Atlanta, GA 30322, USA
bDepartment of Chemistry, Chulalongkorn University, Bangkok 10330, Thailand
Received 31 May 2007; revised 20 June 2007; accepted 21 June 2007
Available online 24 June 2007
Abstract—The Rh(II)-catalyzed reaction of the E-isomer of 2-diazo-3,6-dioxo-6-phenyl-hex-enoic acid methyl ester was carried out
in the presence of various carbonyl compounds and was found to give 1,3-dioxoles in moderate to good yield. In an attempt to pre-
pare the starting a-diazo substrate, an unexpected pseudo-dimerization reaction was encountered when 5-phenyl-furan-2,3-dione
was heated in the presence of sodium methoxide.
Ó 2007 Elsevier Ltd. All rights reserved.
In recent years, a widespread upsurge of activity in the
application of carbonyl ylide dipoles to new synthetic
transformations has occurred.1,2 This research has also
stimulated interest in the use of carbenes and carbenoids
as reactive intermediates for the generation of other
types of ylides.3 A diverse range of chemistry has
already surfaced.1–4 In 1986, work started in the Padwa
laboratory to synthesize bridged oxa-substituted bicy-
cloalkanes from the Rh(II)-catalyzed cyclization cascade
of a-diazo carbonyl compounds.5a The domino reaction
was shown to proceed by the formation of a rhodium
carbenoid intermediate and a subsequent transannular
cyclization of the electrophilic carbon onto an adjacent
carbonyl group to generate a cyclic carbonyl ylide
dipole.5–7 This was followed by a 1,3-dipolar cyclo-
addition reaction with an added dipolarophile A = B
(Scheme 1).
Our ongoing interest in this procedurally simple meth-
odology led us to focus on the cycloaddition behavior
of the related oxidopyrylium dipole 5, where the extra
double bond contained within the ring would not only
allow for the formation of the [5 + 2]-dipolar cyclo-
adduct 6, but also could produce the isomeric cycload-
duct 7. The [5 + 2]-cycloaddition of 3-oxidopyrylium
ylides is a well-precedented reaction and has been used
for the rapid access of functionalized seven-membered
ring structures.8 Henderson and Farina originally dis-
covered that [5 + 2]-cycloadditions can be carried out
by heating acetoxy-pyranones such as 8 and a dipolaro-
phile at 130 °C to afford up to 69% of cycloadduct 10.9
This reaction was further developed by Sammes, who
found that electron rich dipolarophiles were more reac-
tive toward dipole 9 and that the reaction can also be
carried out using Et3N to generate the oxypyrylium
zwitterion at room temperature.10 Substituted allenes11
and dienes12 have also been successfully engaged as
dipolarophiles in intra and intermolecular reactions.
The rapid generation of molecular complexity in a rela-
tively easy manner has made this cycloaddition reaction
extremely useful for the synthesis of seven-membered
ring containing natural products. Notably, Wender
and co-workers have successfully applied this strategy,
in an intramolecular fashion, to the total synthesis of
the natural products phorbol and resiniferatoxin.13 Fur-
ther examples of intramolecular [5 + 2]-cycloadditions
of pyranones of type 11 for natural product synthesis
have also been reported by Heathcock,14 Ohmori,15
Magnus,16 and Williams17 (see Scheme 3).
O
O
-
(CH2)n
A=B
(CH2)n
Rh(II)
RCO(CH2)nCOCHN2
R
O
R
O
1
A
B
+
2
3
Scheme 1.
*
Corresponding authors. Tel.: +1 404 727 0283; fax: +1 404 727 6629
(A.P); e-mail: chemap@emory.edu
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.118

A. Padwa et al. / Tetrahedron Letters 48 (2007) 5938–5941
5939
(80%) and unexpected product obtained from the ther-
mal reaction of 14 under basic conditions was identified
as 3-benzoyl-4-hydroxy-6-phenyl-2H-pyran-2-one (15)
on the basis of its spectral data19 and by the procure-
ment of an X-ray crystal structure. The pseudo-dimer-
ization of 13–15 can be accounted for by an initial
thermal extrusion of carbon monoxide from 13 to give
benzoyl ketene 16 as a transient species. Attack of meth-
oxide anion at the electrophilic ketene center in 16 gen-
erates the stable anion 17, which in turn reacts with
another molecule of the ketene to furnish 1,3-dicarbonyl
anion 18. Cyclization of 18–19 followed by tautomeriza-
tion to the more stable enol form nicely accounts for the
formation of pyranone 15 (Scheme 5).
+
+
R1
O
R2
O
R1
O
R2
-
O O
N2
R2
Rh(II)
?
R1
-
O
5
4
A
B
A
B
R1
O
O
R2
R1
O
R2
O
or
B
A
7
6
Scheme 2.
O
R
+
O
X
O
R
O
O
AcO
O
R
O
O
O
heat
-CO
O
-HOAc
-
O
C
O
O
MeO
Ph
-
X
-
MeO
9
8
10
Ph
H
Ph
17
13
16
O
O
C
O
O
heat
MeO
O
-
R1
R2
R2
heat
H
Ph
RO
O
R1 R3
O
Ph
O
R3
Ph
11
O
Ph
O
O
O
OMe
-
12
-
-MeO
O
O
O
O
Scheme 3.
OH
15
O
Ph
Ph
Ph
18
19
Since we were interested in using the Rh(II)-catalyzed
reaction of a-diazo ketoesters such as 4 as a way to gen-
erate various oxidopyrylium ylides (Scheme 2), we
undertook a study of several methods to synthesize the
required precursor a-diazo ketoesters. To this end, 5-
phenylfuran-2,3-dione (13) was prepared in 80% yield
by reacting trimethyl (1-phenylvinyloxy)silane with oxa-
lyl chloride.18 Our intention was to heat 13 with methyl
acetate in the presence of sodium methoxide with the
hope that we should be able to prepare methyl 3,4,6-tri-
oxo-6-phenylhexanoate acid (14), which would then be
transformed into the corresponding a-diazo ketoester 4
(Scheme 4).
Scheme 5.
In an alternate approach that we next employed for the
preparation of a-diazo ketoester 4, we made use of an
oxidation reaction of furan 20.20 Thus, methyl 2-(fur-
an-2-yl)acetate (20) was treated with mCPBA at 0 °C
in CH2Cl2 and this resulted in a 6:1-stereomeric mixture
of the expected ring-opened butene-diones, which were
immediately converted to the corresponding a-diazo
ketoesters (i.e. 4 and 21) using p-nitrobenzenesulfonyl
azide and Et3N according to the standard Regitz
protocol.21 The two isomeric a-diazo compounds were
separated by fractional recrystallization. Treatment of
the minor Z-isomer 4 with a catalytic quantity of
rhodium(II) acetate in benzene at 25 °C afforded an
unknown dimer (i.e. 22) in 45% yield. Unfortunately,
all of our attempts to trap an oxidopyrylium ylide inter-
mediate from the Z-isomer 4 using various trapping
agents failed to afford any signs of a [5 + 2]-cycloadduct.
The only compound detected in these reactions was
dimer 2222 (see Scheme 6).
O
Ph
O
O
CH2
OSiMe3
oxalyl
O
O
O
Ph
chloride
Ph
OH
Ph
13
15
CH3CO2Me
-
MeO
O O
O O
N2
CO2Me
Ph
We also studied the Rh(II)-catalyzed behavior of the
major E-diazo isomer 21. This isomeric a-diazo keto-
ester cannot undergo internal cyclization to give a car-
bonyl ylide dipole and we were curious as to what
pathway would be followed with this system. Toward
this end, 21 was added to a benzene solution containing
DMAD and a catalytic amount of Rh2(OAc)4 under an
argon atmosphere at 80 °C. The reaction was monitored
Ph
CO2Me
O
4
14
Scheme 4.
However, in our attempts to convert furandione 13 into
14, we encountered a rather unusual reaction. The major

5940
A. Padwa et al. / Tetrahedron Letters 48 (2007) 5938–5941
O O
N2
O
1. mCPBA
Ph
O
Ph
O
CO2Me
Ph
2. NsN3, Et3N
CO2Me
Ph
Rh(II)
O
CO2Me
-
CO2Me
N2
4;
Z
-isomer (11%)
20
21;
E
-isomer (63%)
O
O
R2
+
R1
O
21
Rh2(OAc)4
PhH, rt
R1
R2
Dimer 22
O
O
Scheme 6.
Ph
Ph
CO2Me
O
CO2Me
-
O
O
O
O
R2
R1
Ph
R1
+
R2
O
CO2Me
CO2Me
CO2Me
Ph
Rh(II)
26; R1 = CH2CH2; R2 = N(CH3)CO (25%)
27; R1 = Ph; R2 = H (25%)
28; R1 = R2 = (CH2CH2) (45%)
29; R1 = R2 = CH3 (80%)
30; R1 = OC2H5; R2 = CH3 (80%)
25
CO2Me
N2
O
O
O
OMe
21
23
MeO2C
O
Rh(II)
Scheme 8.
NMe
O
was formed as the major product. We have also shown
that the Rh(II)-catalyzed reaction of the related E-iso-
mer in the presence of various carbonyl compounds
undergoes cyclization to give substituted 1,3-dioxoles
as the major products. An unexpected pseudo-dimeriza-
tion process was also encountered when the thermolysis
of 5-phenyl-2,3-dione was carried out in the presence of
sodium methoxide.
O
Ph
CO2Me
O
O
NMe
O
24
Scheme 7.
Acknowledgements
by TLC and column chromatographic purification of
the crude reaction mixture afforded cycloadduct 23 as
the only isolable product in 42% yield. A related cyclo-
adduct (i.e. 24) was isolated when N-methyl maleimide
was used as the trapping dipolarophile (Scheme 7).
When N-methyl succinimide, benzaldehyde, cyclohexa-
none, or acetone were used as the trapping agents, the
analogous cycloadducts 26–29 were obtained in 25–
80% yield. Ethyl acetate turned out to be a very efficient
trapping agent producing cycloadduct 30 in 80% yield.
The overall cycloaddition can be rationalized by an ini-
tial reaction of a-diazo ketoester 21 with the Rh(II)-cat-
alyst to first generate an electrophilic metallo carbenoid.
This species then reacts with the nucleophilic carbonyl
oxygen atom of the added dipolarophile to furnish the
highly reactive carbonyl ylide intermediate 25. The pres-
ence of the adjacent enone carbonyl group facilitates an
intramolecular [1,5]-electrocyclization that leads to the
corresponding 1,3-dioxole derivatives 26–30.23 A reso-
nance structure of carbonyl ylide with the negative
charge on the oxygen atom of the enone carbonyl group
and a positive charge on the carbonyl C-atom of the
added dipolarophile contributes significantly to the res-
onance hybrid of the transient ylide 25, thereby favoring
the [1,5]-electrocyclization pathway (Scheme 8).
We appreciate the financial support provided by the
National Institutes of Health (GM 059384) and the
National Science Foundation (Grant CHE-0450779).
References and notes
1. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds;
John Wiley and Sons: New York, 1998.
2. (a) Padwa, A.; Hornbuckle, S. F. Chem. Rev. 1991, 91,
263; (b) Padwa, A.; Weingarten, M. D. Chem. Rev. 1996,
96, 223; (c) Padwa, A. Top. Curr. Chem. 1997, 189, 121.
3. (a) Hodgson, D. M.; Pierard, F. Y. T. M.; Stupple, P. A.
Chem. Soc. Rev. 2001, 30, 50; (b) Doyle, M. P. Chem. Rev.
1986, 86, 919; (c) Mehta, G.; Muthusamy, S. Tetrahedron
2002, 58, 9477.
4. Maas, G. Top. Curr. Chem. 1987, 137, 75.
5. (a) Padwa, A.; Carter, S. P.; Nimmesgern, H. J. Org.
Chem. 1986, 51, 1157; (b) Padwa, A.; Stull, P. D.
Tetrahedron Lett. 1987, 28, 5407; (c) Padwa, A.; Austin,
D. J.; Hornbuckle, S. F.; Semones, M. A.; Doyle, M. P.;
Protopopova, M. N. J. Am. Chem. Soc. 1992, 114, 1874;
(d) Padwa, A.; Austin, D. J.; Price, A. T.; Semones, M. A.;
Doyle, M. P.; Protopopova, M. N.; Winchester, W. R. J.
Am. Chem. Soc. 1993, 115, 8669; (e) Padwa, A.; Austin, D.
J.; Hornbuckle, S. F.; Price, A. T. Tetrahedron Lett. 1992,
33, 6427; (f) Padwa, A. Acc. Chem. Res. 1991, 24, 22; (g)
Padwa, A.; Carter, S. P.; Nimmesgern, H.; Stull, P. D. J.
Am. Chem. Soc. 1988, 110, 2894; (h) Padwa, A.; Fryxell,
G. E.; Zhi, L. J. Org. Chem. 1988, 53, 2877; (i) Padwa, A.;
In summary, we have investigated the Rh(II)-catalyzed
reaction of the Z-isomer of 2-diazo-3,6-dioxo-6-phen-
yl-hex-4-enoic acid methyl ester and found that a dimer

A. Padwa et al. / Tetrahedron Letters 48 (2007) 5938–5941
5941
Chinn, R. L.; Zhi, L. Tetrahedron Lett. 1989, 30, 1491; (j)
Padwa, A.; Hornbuckle, S. F.; Fryxell, G. E.; Stull, P. D.
J. Org. Chem. 1989, 54, 817; (k) Dean, D. C.; Krumpe, K.
E.; Padwa, A. J. Chem. Soc., Chem. Commun. 1989, 921;
(l) Padwa, A.; Sandanayaka, V. P.; Curtis, E. A. J. Am.
Chem. Soc. 1994, 116, 2667; (m) Curtis, E. A.; Sandana-
yaka, V. P.; Padwa, A. Tetrahedron Lett. 1995, 36, 1989.
6. (a) Padwa, A.; Brodney, M. A.; Marino, J. P., Jr.;
Sheehan, S. M. J. Org. Chem. 1997, 62, 78; (b) Padwa, A.;
Precedo, L.; Semones, M. J. Org. Chem. 1999, 64, 4079; (c)
Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. J. Org.
Chem. 1997, 62, 1317.
7. (a) Kinder, F. R., Jr.; Bair, K. W. J. Org. Chem. 1994, 59,
6965; (b) Chen, B.; Ko, R. Y. Y.; Yuen, M. S. M.; Cheng,
K.-F.; Chiu, P. J. Org. Chem. 2003, 68, 4195; (c) Hodgson,
D. M.; Avery, T. D.; Donohue, A. C. Org. Lett. 2002, 4,
1809; (d) Dauben, W. G.; Dinges, J.; Smith, T. C. J. Org.
Chem. 1993, 58, 7635.
15. (a) Ohmori, N.; Miyazaki, T.; Kojima, S.; Ohkata, K.
Chem. Lett. 2001, 906; (b) Ohmori, N. J. Chem. Soc.,
Perkin Trans. 1 2002, 755.
16. (a) Bauta, W.; Booth, J.; Bos, M. E.; DeLuca, M.;
Diorazio, L.; Donohoe, T.; Magnus, N.; Magnus, P.;
Mendoza, J.; Pye, P.; Tarrant, J.; Thom, S.; Ujjainwalla,
F. Tetrahedon Lett. 1995, 36, 5327; (b) Bauta, W. E.;
Booth, J.; Bos, M. E.; DeLuca, M.; Diorazio, L.;
Donohoe, T. J.; Frost, C.; Magnus, N.; Magnus, P.;
Mendoza, J.; Pye, P.; Tarrant, J. G.; Thom, S.; Ujjain-
walla, F. Tetrahedron 1996, 52, 14081.
17. Williams, D. R.; Benbow, J. W.; Allen, E. E. Tetrahedron
Lett. 1990, 31, 6769.
18. Saitoh, T.; Oyama, T.; Sakurai, K.; Niimura, Y.; Hinata,
M.; Horiguchi, Y.; Toda, J.; Sano, T. Chem. Pharm. Bull.
1996, 44, 956.
19. (a) Ohta, S.; Tsujimura, A.; Okamoto, M. Chem. Pharm.
Bull. 1981, 29, 2762; (b) Pimenova, E. V.; Zalesov, V. V.;
Kataev, S. S.; Nekrasov, D. D. Russ. J. Gen. Chem. 1997,
67, 630.
20. (a) Gingerich, S. B.; Jennings, P. W. Adv. Oxygenated
Processes 1990, 2, 117; (b) Manfredi, K. P.; Jennings, P.
W. J. Org. Chem. 1989, 54, 5186.
8. For reviews, see: (a) Sammes, P. G. Gazz. Chim. Ital. 1986,
116, 109; (b) Ohkata, K.; Akiba, K. Y. Adv. Heterocycl.
Chem. 1996, 65, 283; (c) Chiu, P.; Leutens, M. Top. Curr.
Chem. 1997, 190, 1; (d) Mascarenas, J. L. Adv. Cyclo-
addition 1999, 6, 1–54.
9. (a) Hendrickson, J. B.; Farina, J. S. J. Org. Chem. 1980,
45, 3359; (b) Hendrickson, J. B.; Farina, J. S. J. Org.
Chem. 1980, 45, 3361.
10. (a) Sammes, P. G.; Street, L. J. J. Chem. Soc., Chem.
Commun. 1982, 1056; (b) Sammes, P. G.; Street, L. J. J.
Chem. Soc., Perkin Trans. 1 1983, 1261; (c) Sammes, P. G.;
Street, L. J.; Kirby, P. J. Chem. Soc., Perkin Trans. 1 1983,
2729; (d) Sammes, P. G.; Street, L. J. J. Chem. Res. Synop.
1984, 196.
21. (a) Regitz, M. Chem. Ber. 1966, 99, 3128; (b) Regitz, M.;
Hocker, J.; Liedhegener, A. Org. Synth. 1973, 5, 179.
22. The reaction of 4 with a number of Rh(II) catalysts in
several solvents and at different concentrations using
diverse trapping agents only led to varying quantities of
dimer 22 together with a tarry residue, which resisted
purification. Our attempts to obtain an X-ray crystal
structure of dimer 22 also failed due to the amorphous
nature of the solid.
11. Lee, H.-Y.; Sohn, J.-H.; Kim, H. Y. Tetrahedron Lett.
2001, 42, 1695.
12. (a) Richter, F.; Maichle-Mossner, C.; Maier, M. E. Synlett
2002, 7, 1097; (b) Rodriguez, J. R.; Castedo, L.; Mascar-
enas, J. L. J. Org. Chem. 2000, 65, 2528.
13. (a) Wender, P. A.; Rice, K. D.; Schnute, M. E. J. Am.
Chem. Soc. 1997, 119, 7897; (b) Wender, P. A.; Jesudason,
C. D.; Nakahira, H.; Tamura, N.; Tebbe, A. L.; Ueno, Y.
J. Am. Chem. Soc. 1997, 119, 12976.
14. Marshall, K. A.; Mapp, A. K.; Heathcock, C. H. J. Org.
Chem. 1996, 61, 9135.
23. For some examples of 1,3-dioxole formation during the
decomposition of diazocarbonyl compounds in the pres-
ence of simple aldehydes and ketones, see: (a) Weigand,
F.; Dworschak, H.; Koch, K.; Konstas, S. Angew. Chem.
1961, 73, 409; (b) Alonso, M. E.; Jano, P. J. Heterocycl.
Chem. 1980, 17, 721; (c) Huisgen, R.; De March, P. J. Am.
Chem. Soc. 1982, 104, 4952; (d) Huisgen, R.; Fisera, L.;
Giera, H.; Sustmann, R. J. Am. Chem. Soc. 1995, 117,
9671; (e) Russell, A. E.; Brekan, J.; Gronenberg, L.;
Doyle, M. P. J. Org. Chem. 2004, 69, 5269; (f) Doyle, M.
P.; Hu, W.; Timmons, D. J. Org. Lett. 2001, 3, 933.