Synthesis and reactions of a novel furo[3,4-d]oxazole

Article abstract of DOI:10.1021/jo980505w

The synthesis of a novel furo[3,4-d]oxazole (7) starting from 2-hydroximino-3-oxopentanedioic acid dimethyl ester (4) and cycloadditions of 7 with dienophiles are reported. Density functional theoretical studies (B3LYP/6-31G) for various c-annulated furans (benzo[c]furan, furo[3,4-d]isoxazole, furo[3,4-f]oxazole, furo[3,4-c￡]thiazole, furo[3,4-6]indole) and their Diels-Aider reactions with model dienophiles (ethylene, acetylene) are in qualitative agreement with experimental data.

Full text of DOI:10.1021/jo980505w

7
680
J . Org. Chem. 1998, 63, 7680-7686
Syn th esis a n d Rea ction s of a Novel F u r o[3,4-d ]oxa zole
Stephan Reck and Willy Friedrichsen*
Institute of Organic Chemistry, University of Kiel, D-24098 Kiel, Germany
Received March 17, 1998
The synthesis of a novel furo[3,4-d]oxazole (7) starting from 2-hydroximino-3-oxopentanedioic acid
dimethyl ester (4) and cycloadditions of 7 with dienophiles are reported. Density functional
theoretical studies (B3LYP/6-31G*) for various c-annulated furans (benzo[c]furan, furo[3,4-d]-
isoxazole, furo[3,4-d]oxazole, furo[3,4-d]thiazole, furo[3,4-b]indole) and their Diels-Alder reactions
with model dienophiles (ethylene, acetylene) are in qualitative agreement with experimental data.
In tr od u ction
Inter- and intramolecular cycloaddition reactions offer
Sch em e 1
1
a rapid access to a wide variety of polycyclic systems.
Furans2 and isobenzofurans (benzo[c]furans) have been
used for this purpose frequently as powerful dienes in
Diels-Alder reactions.5 Suitably substituted isobenzo-
furans (Scheme 1, 1, A ) benzo)-in a number of cases
only prepared in situ- served as starting material for
,3
4
4
,6
polyaromatic hydrocarbons, e.g., 2, 3, inner-function-
alized cavity molecules, natural products (e.g., resisto-
mycin, anthracyclinones ), steroid analogues, oxaster-
7
8
9
10
(
1) (a) Comprehensive Organic Synthesis; Trost, B. M., Ed.; Perga-
mon Press: Oxford, 1991; Vol. 5. (b) Dell, C. P. Contemp. Org. Synth.
997, 4, 87.
1
(2) Dean, F. M. Adv. Heterocycl. Chem. 1981, 30, 168.
(3) (a) Friedrichsen, W.; Pagel, K. Progress in Heterocyclic Chemistry;
Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon Press: Oxford, 1995;
Vol. 7. (b) Reck, S.; Friedrichsen, W. Progress in Heterocyclic Chemistry;
Suschitzky, H., Gribble, G. W., Eds.; Pergamon Press: Oxford, 1996;
Vol. 8. (c) Reck, S.; Friedrichsen, W. Progress in Heterocyclic Chemistry;
Suschitzky, H., Gilchrist, T. L., Eds.; Pergamon Press: Oxford, 1997;
Vol. 9.
(
4) (a) Peters, O.; Friedrichsen, W. Trends Heterocycl. Chem.; 1995,
4
, 217. (b) Elderfield, R. C. Heterocyclic Chemistry; Elderfield, R. C.,
Ed.; Wiley: New York 1951; Vol. 2; p 68. (c) Haddadin, M. J .
Heterocycles 1978, 9, 865. (d) Sargent, M. V.; Cresp, T. M. Compre-
hensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.;
Pergamon Press: Oxford, 1979; Vol. 4; p 693. (e) Friedrichsen, W. Adv.
Heterocycl. Chem. 1980, 26, 135. (f) Wiersum, U. E. Aldrichimica Acta
1
981, 14, 53. (g) Dean, F. M.; Sargent, M. V.; Comprehensive Hetero-
cyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds; Pergamon Press:
Oxford, 1984; Vol. 4, p 531. (h) Sargent, M. V.; Dean, F. M. Compre-
hensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds;
Pergamon Press: Oxford, 1984; Vol. 4; p 599. (i) Donnelly, D. M. X.;
Meegan, M. J . Comprehensive Heterocyclic Chemistry; Katritzky, A.
R., Rees, C. W., Eds; Pergamon Press: Oxford, 1984; Vol. 4; p 657. (j)
Rodrigo, R. Tetrahedron 1988, 44, 2093. (k) Rickborn, B. Advances in
Theoretically Interesting Molecules; Thummel, R. P., Ed.; J AI Press:
Greenwich, CT, 1989; Vol. 1; p 1. (l) Friedrichsen, W. Methoden Org.
Chem. (Houben-Weyl); Kreher, R., Ed.; Thieme Verlag: Stuttgart, 1994;
Vol. E6b1, p 163. (m) Friedrichsen, W. Adv. Heterocyl. Chem., submit-
ted.
(5) (a) Hamer, J . 1,4-Cycloaddition Reactions; Academic Press: New
York, 1967. (b) Wollweber, H. Diels-Alder-Reaktion; Thieme Verlag:
Stuttgart, 1972. (c) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1977,
1
6, 10. (d) Brieger, G.; Bennett, J . N. Chem. Rev. 1980, 80, 63. (e)
Desimoni, G.; Tacconi, G.; Barco, A.; Pollini, G. P.; Natural Products
Synthesis through Pericyclic Reactions; ACS Monograph 180; American
Chemical Society: Washington, DC, 1983. (f) Ciganek, E. Org. React.
oid analogues,11 azasteroid analogues, polycyclic nitrogen
12
1
984, 32, 1. (g) Taber, D. F. Intramolecular Diels-Alder and Alder
13,14
4m,15
heterocycles,
and others.
As has been demon-
Ene Reactions; Springer-Verlag: Berlin, 1984. (h) Fallis, A. G. Can.
J . Chem. 1984, 62, 183. (i) Weinreb, S. M. Acc. Chem. Res. 1985, 18,
strated by Padwa and co-workers, 2-aminoisobenzofurans
offer an ingenious entry into the field of Erythrina
alkaloids using a tandem Diels-Alder N-acyliminium ion
cyclization sequence.16 Progress and success in the field
of isobenzofurans have prompted remarkable activities
in the field of other c-annulated furans (1, Scheme 1; A
1
6. (j) Craig, D. Chem. Soc. Rev. 1987, 16, 187. (k) Roush, W. R.
Advances in Cycloadditions; Curran, D. P., Ed.; J AI Press: Greenwich,
CT, 1990; Vol. 2; p 91.
(
6) (a) Schlicke, B.; Schirmer, H.; Schl u¨ ter, A.-D. Adv. Mater. 1995,
, 544. (b) Kintzel, O.; M u¨ nch, W.; Schl u¨ ter, A.-D.; Godt, A. J . Org.
Chem. 1996, 61, 7304. (b) Meier, H.; Rose, B. Liebigs Ann./ Recueil
997, 663.
7
1
1
0.1021/jo980505w CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/09/1998

Synthesis and Reactions of a Novel Furo[3,4-d]oxazole
J . Org. Chem., Vol. 63, No. 22, 1998 7681
thieno,1
7,18
isoxazolo, furo,20 pyridino, pyridazino,4
indolo
19
4
)
Sch em e 2
4
,21
18,22
benzofuro,
). In this paper we present the
synthesis of furooxazole 7 and some reactions of this
novel c-annulated furan.
Resu lts a n d Discu ssion
As in our previous studies the synthesis of c-annulated
furans could be accomplished by transition metal cata-
lyzed decomposition of 6b (Scheme 1) and subsequent
intramolecular carbene reaction (Hamaguchi-Ibata reac-
tion).23 The starting material 6a was prepared as follows.
Compound 4 is available from dimethyl acetone dicar-
2
4
boxylate with ethyl nitrite/hydrogen chloride. Reduc-
tive acylation25 of 4 gives 5 which, without further
26
2
7
purification, was cyclized to oxazole 6a (19% from
dimethyl acetone dicarboxylate). A diazo group transfer
(
Regitz reaction)28 can be accomplished by a variety of
of 6b with dirhodium tetraacetate in 1,2-dichloroethane
gives 7 in 39% yield (from 6a ) as stable colorless crystals.
Compound 7 seems to be the first reported example of a
furo[3,4-d]oxazole. In line with expectations (see also
Theoretical Investigations) it reacts with typical dieno-
philes such as N-phenylmaleimide and 1,4-naphtho-
quinone to give 8 and 9. Obviously furo[3,4-d]oxazoles
may offer a convenient route to a variety of annulated
benzoxazoles. On treatment of 7 with DMAD, compound
methods. In this case 4-(azidosulfonyl)benzoic acid/
DBU29 proved to be of value, because the resulting
sulfonamide can be separated from the reaction mixture
quite easily. Compound 6b was obtained as an unstable
yellow oil. Transition metal catalyzed decomposition30
(
7) (a) Warrener, R. N.; Wang, S.; Russell, R. A. Tetrahedron 1997,
3, 3975. (b) Warrener, R. N.; Wang, S.; Butler, D. N.; Russell, R. A.
Synlett 1997, 44.
5
(
(
8) Keay, B. A.; Rodrigo, R. J . Am. Chem. Soc. 1982, 104, 4725.
9) Kende, A. S.; Curran, D. P.; Tsay, Y.; Mills, J . E. Tetrahedron
1
2 (Scheme 2) was obtained. The primary adduct (prob-
ably 10) suffers from a ring-opening-rearrangement
Lett. 1977, 3537.
3
1
(
(
10) K o¨ nig, B.-M.; Friedrichsen, W. Tetrahedron Lett. 1987, 28, 4279.
11) Hildebrandt, K.; Debaerdemaeker, T.; Friedrichsen, W. Tetra-
reaction which is well-known in the isobenzofuran, furo-
12,22
19,32,33
[3,4-b]indole,
and furo[3,4-d]isoxazole series.
An
hedron Lett. 1988, 29, 2045.
12) Peters, O.; Friedrichsen, W.; unpublished. Peters, O. Disserta-
tion; University of Kiel, 1996.
13) (a) Peters, O.; Friedrichsen, W. Tetrahedron Lett. 1995, 36,
unusual-although not unexpected-reaction occurs when
7 is treated with p-benzoquinone. After workup red
crystals are obtained which were proved to be compound
(
(
8
581. (b) Kappe, C. O.; Cochran, J . E.; Padwa, A. Tetrahedron Lett.
995, 36, 9285.
(
1
7. Probably in the first step the Diels-Alder adduct
1
14) Padwa, A.; Kappe, C. O.; Cochran, J . E.; Snyder, J . P. J . Org.
Chem. 1997, 62, 2786.
15) (a) Leong-Neumann, S.; Derrick, S. D.; Dibble, P. W. Tetrahe-
14a is formed. Whether there is a tautomeric equilibri-
um 14a h 13a is unknown, but according to density
functional theoretical (DFT) calculations on the model
compounds 13b and 14b (Scheme 3; see Theoretical
Investigations, Table 4), 14b is more favored than 13b
(
dron Lett. 1995, 36, 4181. (b) Berkowitz, D. B.; Maeng, J .-H.; Dantzig,
A. H.; Shepard, R. L.; Norman, B. H. J . Am. Chem. Soc. 1996, 118,
9
7
1
426. (c) Berkowitz, D. B.; Maeng, J . H. Tetrahedron: Asymmetry 1996,
, 1577. (d) Padwa, A.; Cochran, J . E.; Kappe, C. O. J . Org. Chem.
996, 61, 3706.
(∆E (14b - 13b) ) 6.9-8.2 kcal/mol). Ring opening (to
(
16) Padwa, A.; Kappe, C. O.; Reger, T. S. J . Org. Chem. 1996, 61,
888.
17) (a) Sch o¨ ning, A.; Friedrichsen, W. Heterocycles 1986, 24, 307.
15) with subsequent rearrangement may give 16 which
tautomerizes to 17. It is not unreasonable that these last
two steps occur in reversed order (15 f 18 f 17). To
explore the synthetic utility of furo[3,4-d]oxazoles in
intramolecular cycloadditions with unactivated olefins,
the tethered precursors 20a ,b were prepared. Selective
saponification of 6a with KOH gives 19 (Scheme 4) in
4
(
(
(
b) Sch o¨ ning, A.; Friedrichsen, W. Tetrahedron Lett. 1988, 29, 1137.
b) Sch o¨ ning, A.; Friedrichsen, W. Liebigs Ann. Chem. 1989, 405. (c)
Sch o¨ ning, A.; Debaerdemaeker, T.; Zander, M.; Friedrichsen, W. Chem.
Ber. 1989, 122, 1119. (d) Sch o¨ ning, A.; Friedrichsen, W. Z. Naturforsch.
1
989, 44b, 825.
(
18) Kappe, C. O.; Padwa, A. J . Org. Chem. 1996, 61, 6166.
(19) (a) Assmann, L.; Friedrichsen, W. Heterocycles 1989, 29, 1003.
6
7% yield.34 Esterification with allyl alcohol and buten-
1-ol-4 using the Neises-Steglich procedure (DCC/DMAP/
(
b) Assmann, L.; Debaerdemaeker, T.; Friedrichsen, W. Tetrahedron
Lett. 1991, 32, 1161. (c) Assmann, L.; Palm, L.; Zander, M.; Friedrich-
sen, W. Chem. Ber. 1991, 124, 2481. (d) Reck, S.; Bluhm, K.;
Debaerdemaeker, T.; Declercq, J .-P.; Klenke, B.; Friedrichsen, W.
Heterocycles 1996, 43, 1165.
35
CHCl
3
)
gives 20a and 20b, respectively, which can be
transformed to the diazoesters 21a ,b. These latter
(
20) Eberbach, W.; Laber, N.; Bussenius, J .; Fritz, H.; Rihs, G. Chem.
Ber. 1993, 126, 975.
21) Bussenius, J .; Keller, M.; Eberbach, W. Liebigs Ann. Chem.
995, 1503.
22) (a) Gribble, G. W.; Saulnier, M. G. J . Chem. Soc., Chem. Comm.
984, 168. (b) Gribble, G. W.; Saulnier, M. G.; Sibi, M. P.; Obaza-
compounds were obtained as unstable yellow oils. Sub-
(
1
1
(30) Review: Maas, G. Top. Curr. Chem. 1987, 137, 75.
(31) (a) Wittig, G.; Pohlke, R.; Chem. Ber. 1961, 94, 3276. (b) Wittig,
G.; Mayer, U. Chem. Ber. 1963, 96, 329. (c) Wittig, G.; Weinlich, J .;
Wilson, E. R. Chem. Ber. 1965, 98, 458. (d) Wittig, G.; Dorsch, H.-L.
Liebigs Ann. Chem. 1968, 711, 46. (e) Hildebrandt, K.; Dissertation,
University of Kiel, 1988. (f) Cochran J . E.; Padwa, A. Tetrahedron Lett.
1995, 36, 3495.
(
Nutaitis, J . A. J . Org, Chem. 1984, 49, 4518. (c) Nagel, J .; Friedrichsen,
W.; Debaerdemaeker, T. Z. Naturforsch. 1993, 48b, 213. (c) Peters, O.;
Friedrichsen, W. Heterocyc. Comm. 1996, 2, 201.
(
(
(
(
23) Hamaguchi, M.; Ibata, T. Chem. Lett. 1976, 287.
24) Birkhofer, L.; Feldmann, H. Liebigs Ann. Chem. 1964, 677, 150.
25) Procedure: Treibs, A.; Sutter, W.; Chem. Ber. 1951, 84, 76.
26) The corresponding diethyl ester is known: Vidal-Cros, A.
(32) Another type of ring-opening reaction was reported by Hamagu-
2
3
chi and Ibata.
(33) The reaction of furoisoxazoles with DMAD may also yield
1
9
Gaudry, M.; Marquet, A. J . Org. Chem. 1985, 50, 3163.
27) Review: Turchi, I. J .; Dewar, M. J . S. Chem. Rev. 1975, 75,
89.
28) Review: Regitz, M.; Maas, G. Diazo Compounds. Properties and
Synthesis; Academic Press: Orlando, 1986.
29) Hendrickson, J . B.; Wolf, W. A. J . Org. Chem. 1968, 33, 3610.
furooxepines.
(
(34) The same selectivity was observed in the isoxazole series.19 See
also Pl u¨ g, C.; Friedrichsen, W. J . Chem. Soc., Perkin Trans. 1 1996,
1035.
3
(
(35) (a) Neises, B.; Steglich, W.; Angew. Chem., Int. Ed. Engl. 1978,
17, 552. (a) Hassner, A.; Alexanian, V. Tetrahedron Lett. 1978, 4475.
(

7
682 J . Org. Chem., Vol. 63, No. 22, 1998
Reck and Friedrichsen
when Becke’s three parameters41 DFT exchange func-
tional in combination with the Lee, Yang, and Parr
Sch em e 3
4
2
43
correlation functional (B3LYP) together with a 6-31G*
basis44 is used. It has been demonstrated that this hybrid
functional gives optimized geometries for a wide range
4
5
of molecules. Therefore, it can safely be expected that
the bond distances46 given in Table 1 for 7 and the parent
system 32 can be met with trust. Semiempirical methods
AM1, PM3)4
7,48
seem to fail, as were also observed in the
(
furo[3,4-d]isoxazole series. The reactivity of furo[3,4-d]-
oxazoles in Diels-Alder reactions has not been investi-
gated quantitatively, but qualitative observations reveal
that furo[3,4-d]oxazoles are less reactive than benzo[c]-
4
9,50
furans. Recent results obtained by other authors
have shown that transition states of Diels-Alder reac-
tions can be calculated with some confidence by DFT
methods. To get insight into the reactivity of c-annulated
furans, both the thermochemistry as well as the transi-
tion states of the following two series of model reactions
1
-5, 6-10, Scheme 6, Tables 2-4) have been investi-
gated with different quantum chemical methods.
The following results were obtained (Table 2):
(a) Benzofuran (26) is most reactive in both series
(lowest transition state energies). The transition state
for reaction 1 is-in line with expectations-symmetric
with r (7-11) ) r (8-9) ) 2.26 Å (the new formed bonds,
see Figure 1). The reaction centers (C(7), C(8), C(9),
C(11), Figure 1) are slightly pyramidalized. Furo[3,4-d]-
isoxazole (29)19 is of intermediate reactivity in both series
(
reactions 2, 7). Furo[3,4-d]oxazole (32), furo[3,4-d]-
5
1
22
thiazole (35), and furo[3,4-b]indole (38) are least
reactive in both series (reactions 3, 8, 4, 9, and 5, 10,
respectively). The transition state for reaction 3 is
asymmetric with r (5-7) ) 2.19 Å and r (9-10) ) 2.23 Å
(see Figure 2) again with a sligthly pyramidalized ethene.
In both series there is a strong linearity between the
heats of reaction and the corresponding transition state
energies: Highly exothermic reactions point to low
transition state energies (and vice versa), but this linear-
ity holds only for DFT calculations (Table 2). These
results offer the opportunity to take heats of reaction
jection of these precursors to metal-catalyzed decomposi-
tion conditions failed to provide any cycloadduct derived
from a furo[3,4-d]oxazole. Instead, cyclopropane deriva-
tives 22a ,b were formed, albeit in low yields (27% and
2
5%, respectively). It is unclear whether furo[3,4-d]-
(39) Gaussian 92/DFT, Revision G.3, Frisch, M. J .; Trucks, G. W.;
oxazoles of type 23 (Scheme 5) are formed in small
amounts and whether compounds of this type are not
sufficiently reactive to participate in an intramolecular
cycloaddition reaction with an unactivated olefin. From
a purely thermodynamic point of view one can expect that
compounds of type 25 (Scheme 5) are formed with
preference (see Theoretical Investigations, Table 4).
Th eor etica l In vestiga tion s. The detailed structure
of furo[3,4-d]oxazoles is unknown. Quantum chemical
calculations in the furo[3,4-d]isoxazole series revealed
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Wong, M. W.; Foresman,
J . B.; Robb, M. A.; Head-Gorden, M.; Replogle, E. S.; Gomperts, R.;
Andres, J . L.; Raghavachari, K.; Binkley, J . S.; Gonzalez, C.; Martin,
R. L.; Fox, D. J .; Defrees, D. J .; Baker, J .; Stewart, J . J . P.; Pople, J .
A.; Gaussian, Inc.; Pittsburgh, PA, 1993.
(40) Gaussian 94, Revision B.3, Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman,
J . R.; Keith, T.; Peterson, G. A.; Montgomery, J . A.; Raghavachari, K.;
Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Peng,
C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E.
S. Gomperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D.
J .; Baker, J .; Stewart, J . J . P.; Head-Gorden, M.; Gonzalez, C.; Pople,
J . A.; Gaussian, Inc.; Pittsburgh, PA, 1995.
that for the prediction of geometric data (bond distances,
(41) Becke, A. D. Phys. Rev. A 1988, 38, 3098.
(42) Lee, C.; Yang, W.; Parr, G. Phys. Rev. B 1988, 41, 785.
etc.) DFT methods3
6-40
seem to be most reliable especially
(43) Foresman, J . B.; Frisch, Æ. Exploring Chemistry with Electronic
Structure Methods, 2nd ed.; Gaussian, Inc.: Pittsburgh, PA, 1996.
(44) Hehre, W. J .; Radom, L.; Schleyer, P. v. R.; Pople, J . A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986.
(45) Bauschlicher jun., C. W. Chem. Phys. Lett. 1995, 246, 40.
(46) According to all theoretical methods given in Table 1 the furo-
[3, 4-d]oxazole system is completely planar.
(47) Review: Stewart, J . J . P. Reviews in Computational Chemistry;
Lipkowitz, K. B.; Boyd, B. D., Eds.; VCH Publ.: New York, 1990.
(48) The program system MOPAC, version 6.0 was used: QCPE
Bull. 1992, 12, 72.
(
36) (a) Parr, R. G.; Yang, W. Density Functional Theory of Atoms
and Molecules; Oxford University Press: Oxford, 1989. (b) Labanowski,
J . K.; Andzelm, J . W. Density Functional Methods in Chemistry;
Springer-Verlag: New York, 1991. (c) Ziegler, T. Chem. Rev. 1991, 91,
51. (d) Modern Density Functional Theory. A Tool for Chemistry;
Seminario, J . M., Politzer, P., Eds.; Elsevier: Amsterdam, 1995.
6
(37) These calculations were performed with the program systems
38,39 40
GAUSSIAN92
and GAUSSIAN 94.
(38) Gaussian 92, Revision E.2, Frisch, M. J .; Trucks, G. W.; Head-
Gorden, M.; Gill, P. M. W.; Wong, M. W.; Foresman, J . B.; J ohnson, B.
G.; Schlegel, H. B.; Robb, M. A.; Replogle, E. S.; Gomperts, R.; Andres,
J . L.; Raghavachari, K.; Binkley, J . S.; Gonzalez, C.; Martin, R. L.;
Fox, D. J .; Defrees, D. J .; Baker, J .; Stewart, J . J . P.; Pople, J . A.;
Gaussian, Inc.; Pittsburgh, PA, 1992.
(49) Padwa, A.; Kappe, C. O.; Cochran, J . E.; Snyder, J . P.; J . Org.
Chem. 1997, 62, 2786.
(50) J ursic, B. S. J . Org. Chem. 1997, 62, 3046.
(51) Reck, S.; N a¨ ther, C.; Friedrichsen, W. Heterocycles 1998, 48,
853.

Synthesis and Reactions of a Novel Furo[3,4-d]oxazole
J . Org. Chem., Vol. 63, No. 22, 1998 7683
Ta ble 1. Ca lcu la ted Bon d Dista n ces (Å) for 7 a n d 32
a
b
method
AM1 (32)
a
b
c
d
e
f
g
h
i
∆H, E
1.435
1.404
1.360
1.359
1.389
1.408
1.320
1.319
1.262
1.260
1.288
1.291
1.408
1.426
1.400
1.400
1.401
1.395
1.494
1.456
1.411
1.411
1.419
1.408
1.384
1.385
1.357
1.353
1.372
1.356
1.362
1.364
1.334
1.333
1.357
1.372
1.407
1.392
1.358
1.356
1.377
1.409
1.398
1.385
1.350
1.348
1.369
1.352
1.373
1.367
1.341
1.340
1.366
1.377
+27.86
+5.72
-395.18103
-395.27196
-397.46203
-779.19525
PM3 (32)
RHF/6-31G* (32)
RHF/6-311yG** (32)
B3LYP/6-31G* (32)
B3LYP/6-31G* (7)
a
In kcal/mol (AM1, PM3).47,48
b
In au (ab initio and DFT methods).37
Ta ble 2. Tr a n sition Sta te En er gies ∆E(ts) a n d Rea ction En er gies (∆E) a n d En th a lp ies (∆∆H f) for Rea ction s 1-10
(
va lu es in k ca l/m ol)
∆
Eb (∆∆Hf)c
RHF/6-31G*
reaction
∆E(ts - tg)a
AM1
PM3
B3LYP/6-31G*
1
2
3
4
5
6
7
8
9
+15.39
+17.78
+19.63
+19.68
+19.60
+17.77
+20.20
+21.76
+21.90
+21.94
-34.84
-22.86
-23.39
-25.71
-22.15
-28.92
-15.93
-16.49
-19.39
-15.69
-32.47
-21.09
-20.92
-19.50
-22.00
-28.27
-16.39
-16.22
-15.06
-17.57
-36.91
-27.95
-20.02
-23.08
-22.36
-37.23
-25.01
-18.36
-20.22
-19.13
-29.76
-23.40
-19.04
-19.60
-19.02
-34.44
-25.17
-20.24
-21.59
-20.65
1
0
a
Energy difference between the ground state and the transition state. b Reaction energy (ab initio, DFT). c Reaction enthalpy (AM1,
PM3).
Ta ble 3. Rea ction En er gies (∆E)a a n d En th a lp ies (∆Hf)b
for th e F or m a tion of 41-44, 46, a n d 47 (in k ca l/m ol)
systems. DFT methods are valuable quantum chemical
tools for exploring the Diels-Alder reactivity of these
compounds.
∆E, ∆∆Hf
AM1
PM3
6-31G*
B3LYP/6-31G*
Exp er im en ta l Section
4
4
4
4
4
4
1
2
3
4
6
7
-17.44
-20.94
-10.76
-14.27
-29.69
-22.57
-16.63
-17.76
-13.34
-13.58
-30.01
-25.40
-14.18
-17.26
-12.15
-14.89
-10.19
-11.27
-12.75
-13.84
-16.42
-25.98
Gen er a l. Unless otherwise noted, all starting materials
were obtained from commercial suppliers and used without
further purification. Acetonitrile was distilled from CaH
cyclohexane and 1,2-dichloroethane were distilled from P
and chloroform and EtOAc were distilled from CaCl /K CO
2
5
3
,
,
.
2
O
2
2
a
Reaction energies (ab initio, DFT). b Reaction enthalpies (AM1,
5
-(Meth oxycar bon yl)-2-m eth yloxazole-4-car boxylic acid
PM3).
m eth yl ester (6a ): 2-Hydroximino-3-oxopentanedioic acid
dimethyl ester was prepared starting from 45.0 g (0.26 mol)
of acetone dicarboxylic acid dimethyl ester following the
reported method.24 The obtained green-yellow oil was dis-
solved in acetic acid (150 mL) and acetic anhydride (75 mL).
Zinc dust (56 g, 0.86 mol) was added portionwise so that the
temperature stayed below 40 °C (cooling with ice/salt bath).
After stirring for 10 min, 150 mL of water was added dropwise
at such a rate that the temperature again stayed below 40
calculated for two or more strongly related reactions with
DFT methods mentioned above as a qualitive tool for
Diels-Alder reactions of c-annulated furans (and other
compounds). In line with this reasoning are the results
of the reactions which lead to 41-44, and 46, and 47
(Scheme 7, Table 3): (1) 1-Alkoxy-3-alkoxycarbonyl sub-
stituted c-annulated furans are less reactive than their
unsubstituted counterparts; (2) Furo[3,4-d]oxazoles and
°
C. After additional stirring for 2 h at room temperature, the
reaction mixture was filtered, the filter cake was washed with
water (2 × 60 mL), and the combined filtrates were extracted
with chloroform (5 × 100 mL). The collected organic layers
-
[
thiazoles are less reactive than the corresponding benzo-
c]furan.
were washed with water (2 × 75 mL), dried (Na
2 4
SO ), and
concentrated in vacuo to give 2-(acetylamino)-3-oxopentanedio-
ic acid dimethyl ester as crude orange oil (42.3 g, 71%). This
oil was dissolved in 150 mL of chloroform, and after cooling to
5 °C ,20 mL (0.27 mol) of thionyl chloride was added. The ice
bath was removed, and the mixture was slowly heated to
reflux. After gas evolution ceased, the solution was allowed
to come to room temperature and then concentrated in vacuo.
The residue was dissolved in ether and washed with saturated
Con clu sion
The Hamaguchi-Ibata reaction proved to be of value
for the synthesis of furo[3,4-d]oxazoles and other c-
annulated furans (benzo[c]furans, furo[3,4-d]isoxazoles,
5
1
furo[3,4-b]indoles, furo[3,4-d]thiazoles ) and comple-
ments other methods for the preparation of these
compounds4 (e.g., Pummerer-induced cyclization of sul-
foxides). Generally speaking heteroannulated furans are
less reactive than benzo[c]furans but may nevertheless
serve as an entry to heteroannulated polycyclic ring
3 2 4
NaHCO solution, dried over Na SO , and purified by column
m
chromatography (silica gel, cyclohexane/EtOAc (1:1)) to give,
after recrystallization, oxazole 6a as colorless needles (11.3 g,
19% overall yield): mp 69-70 °C; IR (KBr) ν 1741, 1716, 1635
-
1
1
cm ; H NMR (CDCl ) δ 2.49 (s, 3H), 3.75 (s, 3H), 3.90 (s,
3

7
684 J . Org. Chem., Vol. 63, No. 22, 1998
Reck and Friedrichsen
Ta ble 4. DF T En er giesa ,b for Com p ou n d s 7, 13, 14, 23, 25-47 a n d th e Tr a n sition Sta tes of Rea ction s 1-10c (in a u )
compound
compound
compound
reaction
7
-779.19425
-778.91373
-778.92473
-778.92673
-817.24495
-817.31796
-383.65037
-462.28524
-461.03090
-397.42339
30
31
32
33
34
35
36
37
38
39
476.04814
-474.78915
-397.46203
-476.07983
-474.81992
-720.45081
-799.06951
-797.81086
-515.21817
-593.83594
40
41
42
43
44
45
46
47
-592.57673
-857.79795
-1180.78580
-856.54022
-1179.52807
-726.06082
-804.67445
-803.42787
1
2
3
4
5
6
7
8
9
-462.21329
-475.98251
-476.01820
-799.00691
-593.77440
-460.94769
-474.71685
-474.75299
-797.74156
-592.50885
1
1
1
2
2
2
2
2
2
3b
4b; endo
4b; exo
3
5
6
7
8
9
10
a
B3LYP/6-31G*. b Ethene: -78.587457 au; acetylene: -77.325645 au. c The Hesse matrix of the transition states showed one negative
eigenvalue.
Sch em e 4
Sch em e 6
Sch em e 5
3
(
H), 4.10 (s, 2H); 13C NMR (CDCl
q), 52.1 (q), 128.9 (s), 151.1 (s), 160.3 (s), 161.8 (s), 167.7 (s);
3
) δ 14.0 (q), 31.4 (t), 51.6
F igu r e 1. Transition state of reaction 1 (Scheme 6; B3LYP/
6
-31G*).
+
MS (EI, 70 eV) m/z 213 (21, M ), 181 (100), 154 (73), 150 (21);
HRMS calcd for C 213.0637, found 213.0635. Anal.
Calcd for C : C, 50.71; H, 5.20; N, 6.57. Found: C,
0.95; H, 5.19; N, 6.65.
-Meth oxy-2-m eth ylfu r o[3,4-d]oxazole-6-car boxylic Acid
9
H11NO
5
9
H11NO
5
5
4
Meth yl Ester (7). A suspension of 4-(azidosulfonyl)benzoic
acid (1.76 g, 7.5 mmol) in a solution of oxazole 6a (1.5 g, 7.0
mmol) in 70 mL of acetonitrile was cooled under nitrogen to 0
°
C. To this mixture 2.43 mL (16.3 mmol) of DBU was added.
The acid dissolved immediately, the solution became dark red,
and, after a short period, the DBU salt of 4-sulfamoylbenzoic
acid precipitated. After stirring for 1 h at room temperature,
the precipitate was filtered off, and the filtrate was purified
by chromatography over silica gel eluting with EtOAc. The
yellow solution of 5-(diazo(methoxycarbonyl)methyl)-2-methyl-
oxazole-4-carboxylic acid methyl ester 6b was concentrated
carefully in vacuo (bath temperature below 30 °C) to obtain
F igu r e 2. Transtion state of reaction 3 (Scheme 6; B3LYP/
-31G*).
6
6
b as a yellow oil, which shows slow decomposition. IR (film)
was dissolved immediately after isolation in 75 mL of 1,2-
dichloroethane. This solution was dropped under nitrogen in
1 h to a suspension of Rh (OAc) (1.5 mg) in 1,2-dichloroethane
2 4
(100 mL) heated to reflux. After refluxing for additional 30
min, the reaction mixture was cooled to room temperature,
concentrated in vacuo, filtered over silica gel, and purified by
-1 1
ν 2955, 2125, 1717, 1606 cm ; H NMR (CDCl
3
5
3
) δ 2.55 (s, 3H),
) δ 13.2 (q), 51.4 (q),
1.9 (q), 126.9 (s), 142.5 (s), 160.6 (s), 161.8 (s), 162.4 (s) (signal
.86 (s, 3H), 3.93 (s, 3H); 13C NMR (CDCl
3
+
for CN
2
not observed); MS (EI, 70 eV) m/z 239 (4, M ), 211
(70), 180 (9), 168 (15), 140 (100), 112 (22). The diazoester 6b

Synthesis and Reactions of a Novel Furo[3,4-d]oxazole
J . Org. Chem., Vol. 63, No. 22, 1998 7685
Sch em e 7
C
19
H
13NO
6
: C, 64.96; H, 3.73; N, 3.99. Found: C, 64.55; H,
3
.76; N, 3.91.
-Met h oxy-2-m et h yl-7-oxo-7H -b en zoxa zole-5,6,6-t r i-
4
ca r boxylic Acid Tr im eth yl Ester (12). A solution of
furooxazole 7 (520 mg, 2.5 mmol) and DMAD (874 mg, 6.2
mmol) in chloroform (40 mL) was heated to reflux for 1.5 h.
After cooling to room temperature and evaporation of the
solvent, the residual oil was filtered over silica gel and purified
by radial chromatography (silica gel, cyclohexane/EtOAc 5:1).
Crystallization from ether/pentane yields 12 as nearly colorless
crystals (269 mg, 31%): mp 163-164 °C; IR (KBr) ν 1785,
-
1
1
1
(
5
(
745, 1715, 1687 cm ; H NMR (CDCl
s, 6 H), 3.83 (s, 3H), 4.16 (s, 3H); 13C NMR (CDCl
2.6 (q), 54.0 (q), 61.6 (q), 72.2 (s), 117.5 (s), 143.6 (s), 148.7
s), 152.3 (s), 164.1 (s), 164.3 (s), 168.9 (s), 173.8 (s); UV (MeCN)
λ (log ꢀ) 240 (4.304), 333 (3.439); MS (EI, 70 eV) m/z 353 (21,
3
) δ 2.66 (s, 3H), 3.79
3
) δ 14.8 (q),
+
M ), 322 (13), 309 (64), 294 (100); HRMS calcd for C15
H
15NO
9
;
3
5
53.07468, found 353.07440. Anal. Calcd for C15
1.00; H, 4.28; N, 3.96. Found: C, 50.90; H, 4.33; N, 3.87.
,8-Dih yd r oxy-4-m eth oxy-2-m eth yl-9-oxo-9H-n a p h th o-
2,3-d ]oxa zole-9a -ca r boxylic Acid Meth yl Ester (17). A
H
15NO : C,
9
5
[
solution of furooxazole 7 (500 mg, 2.3 mmol) and p-benzo-
quinone (761 mg, 7.0 mmol) in chloroform (30 mL) was heated
under nitrogen for 6 h to reflux. After chromatographic
workup compound 17 was obtained from ether/n-pentane as
red crystals (68 mg, 9%): mp 169 °C (decomp); IR (KBr) ν 3422,
-
1
1
2
(
7
964, 1737, 1719, 1633, 1594 cm ; H NMR (CDCl
3
) δ 2.31
s, 3H), 3.71 (s, 3H), 4.28 (s, 3H), 6.85 (d, 1H, J ) 9.2 Hz),
1
3
.11 (d, 1H, J ) 9.2 Hz), 8.43 (s, 1H), 11.02 (s, 1H); C NMR
) δ 14.7 (q), 54.3 (q), 61.3 (q), 88.6 (s), 110.0 (s), 116.2
s), 120.9 (d), 127.0 (s), 130.4 (d), 137.7 (s), 148.5 (s), 157.1 (s),
(CDCl
3
radial chromatography (silica gel, cyclohexane/EtOAc 2:1).
After recrystallization from ether/pentane, furan 7 is obtained
as fine colorless needles (580 mg, 39%): mp 133-134 °C; IR
(
1
65.8 (s), 168.6 (s), 195.6; UV (MeCN) λ (log ꢀ) 235 (4.188),
-
1
1
261 (4.247), 293 (3.905, sh), 380 (3.428), 454 (3.661); MS (EI,
70 eV) m/z 319 (15, M ), 304 (19), 260 (100), 245 (20); HRMS
calcd for C15
for C15 13NO
5-Ca r boxym eth yl-2-m eth yl-oxa zole-4-ca r boxylic Acid
Meth yl Ester (19). A solution of oxazole 6a (3.00 g, 14.1
mmol) in 80 mL of methanol was treated with KOH (946 mg,
(
KBr) ν 1720, 1670, 1633, 1580 cm ; H NMR (CDCl
3
) δ 2.54
) δ 14.7 (q),
1.5 (q), 59.0 (q), 110.9 (s), 115.2 (s), 146.5 (s), 152.3 (s), 157.2
s), 168.0 (s); UV (MeCN) λ (log ꢀ) 215 (4.266), 287 (4.430);
+
1
3
(
5
(
s, 3H), 3.89 (s, 3H), 4.23 (s, 3H); C NMR (CDCl
3
H
13NO
7
; 319.06921, found 319.06910. Anal. Calcd
H
7
: C, 56.43; H, 4.10. Found: C, 56.29; H, 4.19.
+
MS (EI, 70 eV) m/z 211 (70, M ), 180 (16), 168 (11), 140 (100);
HRMS calcd for C
Calcd for C NO
9
H
9
NO
5
, 211.0481, found 211.0478. Anal.
9
H
9
5
: C, 51.19; H, 4.30; N, 6.63. Found: C,
1
6.9 mmol), heated to reflux for 4 h, cooled to room temper-
ature, and neutralized with 1.9 mL (16.9 mmol) of 60%
perchloric acid. The precipitate of KClO was filtered off and
5
1.19; H, 4.27; N, 6.53.
-Met h oxy-2-m et h yl-5,7-d ioxo-6-p h en yl-6,7-d ih yd r o-
H-oxa zolo[4,5-f]isoin d ole-8-ca r boxylic Acid Meth yl Es-
4
4
5
the filtrate concentrated in vacuo. Recrystallization from
methanol/ether gives 19 as a colorless solid (1.87 g, 67%): mp
ter (8). A solution of furooxazole 7 (600 mg, 2.8 mmol) and
N-phenylmaleimide (1.48 g, 8.5 mmol) in chloroform (50 mL)
was heated to reflux for 2 h. Removal of the solvent and
chromatographic workup yield compound 8 as colorless crys-
tals (239 mg, 23%): mp 217-218 °C; IR (KBr) ν 1764, 1718,
-1
1
44-145 °C; IR (KBr) ν 3422, 1737, 1719, 1633, 1594 cm ;
1
H NMR (DMSO-d
6
) δ 2.42 (s, 3H), 3.77 (s, 3H), 4.01 (s, 2H);
) δ 13.4 (q), 32.3 (t), 51.8 (q), 128.2 (ss),
13
C NMR (DMSO-d
53.1 (st), 160.2 (sq), 162.0 (sq), 169.4 (st) MS (EI, 70 eV) m/z
6
1
1
NO
-
1 1
1
4
(
(
1
710, 1618 cm ; H NMR (CDCl
3
) δ 2.70 (s, 3H), 4.04 (s, 3H),
+
89 (1, M ), 168 (7) 155 (37), 123 (100). Anal. Calcd for C
: C, 48.25; H, 4.55; N, 7.03. Found: C, 48.20; H, 4.51; N,
.01.
-[(Allyloxyca r b on yl)m et h yl]-2-m et h yloxa zole-4-ca r -
boxylic Acid Meth yl Ester (20a ). To a solution of oxazole
9 (1.50 g, 7.5 mmol), allylic alcohol (569 mg, 9.8 mmol), and
dimethylamino)pyridine (DMAP) (60 mg, 0.5 mmol) in 75 mL
of chloroform 2.02 g (9.8 mmol) of dicyclohexyl carbodiimide
DCC) were added. After stirring for 2 days, the mixture was
8 9
H -
.62 (s, 3H), 7.36-7.40 (m, 1H), 7.42-7.44 (m, 2H), 7.47-7.50
5
1
3
m, 2H); C NMR (CDCl
s), 109.6 (s), 113.6 (s), 126.7 (d), 127.4 (s), 128.1 (d), 129.0 (d),
31.5 (s), 135.6 (s), 150.6 (s), 153.9 (s), 163.0 (s), 164.6 (s), 165.2
s); UV (MeCN) λ (log ꢀ) 247 (4.972), 370 (3.914); MS (EI, 70
3
) δ 14.7 (q), 53.3 (q), 61.9 (q), 107.9
7
5
(
1
(
+
eV): m/z 366 (91, M ), 335 (21), 306 (100). HRMS calcd for
C
C
19
H
H
14
N
N
2
O
O
6
, 366.08517, found 366.08500. Anal. Calcd for
: C, 62.30; H, 3.85; N, 7.65. Found: C, 62.85; H,
19
14
2
6
(
3
.90; N, 7.51.
-Met h oxy-2-m et h yl-5,10-d ioxoa n t h r a [2,3-d ]oxa zole-
1-ca r boxylic Acid Meth yl Ester (9). 1,4-Naphthoquinone
filtered and the solvent was removed in vacuo. Chromato-
graphic workup (silica gel, cyclohexane/EtOAc 1:1) gives 20a
as a colorless oil (667 mg, 37%): IR (film) ν 1743, 1714, 1627,
4
1
-
1 1
(1.62 g, 10.2 mmol) was added to a solution of 720 mg (3.4
1595, 1440 cm ; H NMR (CDCl ) δ 2.49 (s, 3H), 3.90 (s, 3H),
3
mmol) of furooxazole 7 in chloroform (50 mL) and the solution
heated under nitrogen for 3 h. The reaction mixture was
concentrated in vacuo and purified by column chromatography
4.13 (s, 2H), 4.65 (dt, 2H, J ) 5.72, J ) 1.40 Hz), 5.26 (dq, 1H,
J ) 10.42, J ) 1.27 Hz), 5.32 (dq, 1H, J ) 17.21, J ) 1.50 Hz),
1
3
5.91 (ddt, 1H, J ) 17.20, J ) 10.41, J ) 5.73 Hz); C NMR
(silica gel, cyclohexane/EtOAc 2:1). Recrystallization from
(CDCl ) δ 13.5 (q), 31.7 (t), 51.8 (q), 65.8 (t), 118.4 (t), 129.0
3
dichloromethane/pentane gives 9 as yellow crystals (240 mg,
(s), 131.3 (d), 151.1 (s), 160.5 (s), 162.0 (s), 167.1 (s); UV
-
1
2
4%): mp 224-225 °C; IR (KBr) ν 1728, 1668, 1602, 1261 cm
;
(MeCN) λ (log ꢀ) 214 (3.905), 230 (3.949); MS (EI, 70 eV) m/z
239 (12, M ), 183 (8), 154 (100); HRMS calcd for C11
239.07938, found 239.07930.
5-[(Bu t-3-en yloxyca r bon yl)m eth yl]-2-m eth yloxa zole-4-
ca r boxylic a cid m eth yl ester (20b) was prepared from
oxazole 19 (1.80 g, 9.1 mmol), 3-buten-1-ol (846 mg, 11.8
mmol), DMAP (71 mg, 0.6 mmol), and DCC (2.42 g, 11.8 mmol)
in 80 mL of chloroform following the method for 20a . Com-
pound 20b was obtained as a colorless oil (579 mg, 25%): IR
1
+
H NMR (CDCl
7
5
3
) δ 2.70 (s, 3H), 4.10 (s, 3H), 4.59 (s, 3H), 7.70-
.82 (m, 2H), 8.16-8.27 (m, 2H); 13C NMR (CDCl
) δ 14.6 (q),
3.4 (q), 62.1 (q), 112.0 (s), 119.5 (s), 126.8 (d), 127.3 (d), 129.9
5
H13NO ;
3
(
1
s), 132.1 (s), 133.3 (d), 134.6 (d), 135.0 (s), 135.8 (s), 152.1 (s),
53.7 (s), 165.2 (s), 166.3 (s), 181.7 (s), 182.4 (s); UV (MeCN)
λ (log ꢀ) 245 (4.869), 265 (4.466), 325 (3.653), 375 (3.728); MS
+
(EI, 70 eV) m/z 351 (80, M ), 322 (100), 290 (13); HRMS calcd
for C19 , 351.07428, found 351.074028. Anal. Calcd for
H
13NO
6

7
686 J . Org. Chem., Vol. 63, No. 22, 1998
Reck and Friedrichsen
(
(
(
film) ν 1742, 1714, 1627, 1595 cm-1; 1H NMR (CDCl
3
) δ 2.39
(dddd, 1H, J ) 8.0, J ) 5.3, J ) 4.6, J ) 0.7 Hz), 3.91 (s, 3H),
4.34 (dt, 1H, J ) 9.3, J ) 0.6 Hz), 4.64 (ddt, 1H, J ) 9.3, J )
tq, 2H, J ) 6.71, J ) 1.36 Hz), 2.48 (s, 3H), 3.90 (s, 3H), 4.09
s, 2H), 4.20 (t, 2H, J ) 6.70 Hz), 5.07 (ddt, 1H, J ) 10.37, J
4.7, J ) 0.5 Hz); 13C NMR (CDCl
) δ 13.6 (q), 17.2 (t), 24.6 (s),
3
)
1.80, J ) 1.18 Hz), 5.10 (ddd, 1H, J ) 17.15, J ) 3.29, J )
26.6 (d), 51.9 (q), 68.2 (t), 130.8 (s), 151.1 (s), 160.8 (s), 161.5
1
.55 Hz), 5.75 (ddt, 1H, J ) 17.01, J ) 10.30, J ) 6.76 Hz);
(s), 172.6 (s); UV (MeCN) λ (log ꢀ) 206 (3.862), 238 (3.924);
1
3
+
C NMR (CDCl
3
) δ 13.4 (q), 31.6 (t), 32.6 (t), 51.6 (q), 64.2 (t),
MS (EI, 70 eV) m/z 237 (59, M ), 222 (11), 205 (100), 176 (18);
1
17.1 (t), 128.8 (s), 133.4 (d), 151.3 (s), 160.3 (s), 161.8 (s), 167.3
HRMS calcd for C11
H
11NO 237.06372, found 237.06370.
5
:
(
s); UV (MeCN) λ (log ꢀ) 214 (3.901), 228 (3.929); MS (EI, 70
Anal. Calcd for C11
Found: C, 56.28; H, 4.69; N, 5.85.
H
11NO : C, 55.70; H, 4.67; N, 5.90.
5
+
eV) m/z 253 (19, M ), 238 (22), 194 (10), 181 (12), 154 (100);
HRMS calcd for C12 : 253.09502, found 253.09500.
-Meth yl-5-(2-oxo-3-oxa bicyclo[3.1.0]h ex-1-yl)oxa zole-
4
4
of oxazole 20a (667 mg, 3.1 mmol) in acetonitrile (50 mL) was
cooled to 0 °C under nitrogen. To this mixture was added 0.96
mL (6.5 mmol) of DBU. The acid dissolved immediately, and,
after a short period, the DBU salt of 4-sulfamoyl-benzoic acid
precipitated. After stirring for 1 h at room temperature, the
precipitate was filtered off, and the filtrate was purified by
chromatography over silica gel eluting with EtOAc. The yellow
solution of 21a was concentrated carefully in vacuo (bath
temperature below 30 °C) and dissolved immediately in 1,2-
dichloroethane (50 mL). This solution was dropped over 1 h
H
15NO
5
2-Meth yl-5-(2-oxo-3-oxa bicyclo[4.1.0]h ep t-1-yl)oxa zole-
4-ca r boxylic a cid m eth yl ester (22b) was prepared from
oxazole 20b (733 mg, 2.9 mmol), 4-(azidosulfonyl)benzoic acid
(723 mg, 3.2 mmol), and DBU (1.0 mL, 6.7 mmol) following
the procedure for 22a . Colorless crystals (179 mg, 25%): mp
165-166 °C (from ether/n-pentane); IR (KBr) ν 1712, 1625,
2
-ca r boxylic Acid Meth yl Ester (22a ). A suspension of
-(azidosulfonyl)benzoic acid (697 mg, 3.1 mmol) in a solution
-
1 1
1586 cm ; H NMR (CDCl ) δ 1.77-1.82 (m, 1H), 2.00-2.14
3
(m, 3H), 2.48 (s, 3H), 2.53-2.62 (m, 1H), 3.90 (s, 3H), 4.24 (ddd,
1H, J ) 12.9, J ) 11.9, J ) 3.4 Hz), 4.44 (dddd, 1H, J ) 11.9,
J ) 5.9, J ) 1.80, J ) 1.48 Hz); 13C NMR (CDCl
) δ 13.9 (q),
3
15.2 (t), 20.6 (t), 22.0 (s), 24.9 (d), 52.0 (q), 65.2 (t), 129.6 (s),
155.4 (s), 160.3 (s), 161.8 (s), 168.5 (s); UV (MeCN) λ (log ꢀ)
206 (3.839), 234 (3.877); MS (EI, 70 eV) m/z 251 (34, M ), 223
(26), 219 (100), 191 (24), 189 (29); HRMS calcd for C12
+
H
H
13
-
-
under nitrogen to a suspension of 1.5 mg of Rh
2
(OAc)
4
in 1,2-
NO
NO
5
: 251.07938, found 251.07940. Anal. Calcd for C12
: C, 57.37; H, 5.22; N, 5.58. Found: C, 57.42; H, 5.27; N,
13
dichloroethane (75 mL) heated to reflux. After refluxing for
an additional 30 min, the reaction mixture was cooled to room
temperature, concentrated in vacuo, filtered over silica gel, and
purified by chromatography (silica gel, cyclohexane/EtOAc 1:1).
Recrystallization from ether/pentane gives 22a as colorless
crystals (183 mg, 27%): mp 135-136 °C; IR (KBr) ν 1758,
5
5.53.
Ack n ow led gm en t. The support of this work by the
Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie is gratefully acknowledged.
-
1 1
1
1
740, 1586 cm ; H NMR (CDCl
3
) δ 1.51 (t, 1H, J ) 5.4 Hz),
.98 (ddt, 1H, J ) 8.0, J ) 5.5, J ) 0.5 Hz), 2.49 (s, 3H), 2.57
J O980505W