Angewandte
Chemie
Table 3: Furans 4 obtained from 1,2-dihydrofurans 3.
also has been isolated. Further studies are underway to
determine the scope, mechanism, and synthetic applications
of these novel cyclization reactions.
Received: December 21, 2006
Revised: February 19, 2007
Published online: April 17, 2007
Entry
3
R1
R2
R3
R4
4
Yield [%][a]
=
1
2
3
4
5
6
7
8
3c
3d Me
3e
3j
3k
3l
Me
H
H
H
H
H
H
À
H
H
H
H
Me
Ph
(E)-PhCH CH
4c[b] 94
4d[d] 87
Keywords: carbenes · cycloaddition · furans · rearrangement ·
synthetic methods
.
=
(E)-FcCH CH
[c]
=
Me
Me
H
H
H
(E)-2-FuCH CH
4e
85
69
Ph
4j[e]
=
(E)-PhCH CH
4k[f] 55
=
(E)-PhCH CH
4l
4m
4o
62
80
71
[1] Metal Carbenes in OrganicSynthesis , Vol. 13 (Ed.: K. H. Dötz),
Springer, Berlin, 2004.
À
=
3m
3o
(CH2)4
H
(E)-PhCH CH
H
H
Fc
[2] a) E. O. Fischer, K. H. Dötz, Chem. Ber. 1970, 103, 1273 – 1278;
b) K. H. Dötz, E. O. Fischer, Chem. Ber. 1972, 105, 1356 – 1367.
[3] For isolated examples of cyclopropanation reactions of electron-
poor olefins with particular types of aminocarbene complexes,
see: a) R. Aumann, H. Heinen, C. Krüger, P. Betz, Chem. Ber.
1990, 123, 605 – 610; b) I. Merino, L. S. Hegedus, Organometal-
lics 1995, 14, 2522 – 2531; c) J. Barluenga, F. Aznar, A. Martín,
Organometallics 1995, 14, 1429 – 1433; d) P. J. Campos, A.
Soldevilla, D. Sampedro, M. A. Rodríguez, Org. Lett. 2001, 3,
4087 – 4089.
[4] a) A. Wienand, H.-U. Reissig, Tetrahedron Lett. 1988, 29, 2315 –
2318; b) J. W. Herndon, S. U. Tumer, Tetrahedron Lett. 1989, 30,
4771 – 4774; c) A. Wienand, H.-U. Reissig, Organometallics
1990, 9, 3133 – 3142; d) D. F. Harvey, M. F. Brown, Tetrahedron
Lett. 1990, 31, 2529 – 2532; e) A. Wienand, H.-U. Reissig, Chem.
Ber. 1991, 124, 957 – 965; f) J. W. Herndon, S. U. Tumer, J. Org.
Chem. 1991, 56, 286 – 294; g) M. Hoffmann, H.-U. Reissig,
Synlett 1995, 625 – 627; h) M. A. Sierra, J. C. del Amo, M. J.
Mancheæo, M. Gómez-Gallego, Tetrahedron Lett. 2001, 42,
5435 – 5438; i) J. Barluenga, M. A. Fernµndez-Rodríguez, P.
García-García, E. Aguilar, I. Merino, Chem. Eur. J. 2006, 12,
303 – 313; see also: j) M. D. Cooke, E. O. Fischer, J. Organomet.
Chem. 1973, 56, 279 – 284; k) J. Barluenga, K. Muæiz, A.
Ballesteros, S. Martínez, M. Tomµs, Arkivoc 2002, 3, V, 110– 119.
[5] a) J. Barluenga, M. Tomµs, A. L. Suµrez-Sobrino, Synthesis 2000,
935 – 940; b) J. Barluenga, A. L. Suµrez-Sobrino, M. Tomµs, S.
García-Granda, R. Santiago-García, J. Am. Chem. Soc. 2001,
123, 10494 – 10501.
[a] Yield of isolated analytically pure product 4 based on the correspond-
ing 3. [b] Hexane/EtOAc (20:1) was used as solvent instead of Et2O.
[c] Fu=furyl. [d] Reaction carried out by treatment with silica gel in
hexane/EtOAc (20:1) at RT. [e] Reaction carried out in the absence of
silica gel. [f] Solvent: EtOAc instead of Et2O.
by exposure of a solution of 3 in THF at room temperature to
a catalytic amount of hydrochloric acid (0.5n aqueous
solution; Scheme 3a). Moreover, the 1,4-diketone 6i was
[6] a) J. Barluenga, M. Tomµs, J. A. López-Pelegrín, E. Rubio, J.
Chem. Soc. Chem. Commun. 1995, 665 – 666; for the formation
of pyrroles by heating for longer times, see: b) T. N. Danks, D.
Velo-Rego, Tetrahedron Lett. 1994, 35, 9443 – 9444.
Scheme 3. 1,4-Dicarbonyl compounds 6 generated from 1,2-dihydro-
furans 3.
[7] For the cyclopropanation of electron-poor 1,3-dienes (EWG =
CO2Me, CONMe2, CN) with FCCs, see: a) M. Buchert, H.-U.
Reissig, Tetrahedron Lett. 1988, 29, 2319 – 2320; b) M. Buchert,
H.-U. Reissig, Chem. Ber. 1992, 125, 2723 – 2729; c) M. Buchert,
M. Hoffmann, H.-U. Reissig, Chem. Ber. 1995, 128, 605 – 614; for
formed when the 3,3-disubstituted dihydrofuran 3i (for which
elimination of methanol is not possible) was subjected to
purification by column chromatography with normal silica gel
(Scheme 3b). While furans 4 are the products from the formal
aromatic [4E+1C] cycloaddition reaction between an FCC and
an enone or enal, the 1,4-dicarbonyl compounds 6 (with an
umpolung pattern of reactivity)[19] represent the formal
Michael adduct of an acyl anion equivalent to an enone/
enal, the synthetically equivalent reagent being the chromium
carbene complex (the electrophilic carbene carbon atom).[20]
This synthetic equivalence has been previously recognized.[4c]
In summary, we have developed the first successful
thermal reaction between Fischer carbene complexes and
enones or enals. This process leads to 2-methoxy-2,3-dihy-
drofurans by ring enlargement of the corresponding formyl-
or acylcyclopropanes. A stable tricyclic cyclopropyl ketone
=
the cyclopropanation of the N N bond of electron-deficient azo
compounds with FCCs, see: d) C. Tata Maxey, L. McElwee-
White, Organometallics 1991, 10, 1913 – 1916.
[8] J. Barluenga, S. López, A. A. Trabanco, A. Fernµndez-Acebes, J.
Flórez, J. Am. Chem. Soc. 2000, 122, 8145 – 8154.
[9] a) J. Barluenga, S. López, J. Flórez, Angew. Chem. 2003, 115,
241 – 243; Angew. Chem. Int. Ed. 2003, 42, 231 – 233; b) F.
Zaragoza Dörwald, Angew. Chem. 2003, 115, 1372 – 1374;
Angew. Chem. Int. Ed. 2003, 42, 1332 – 1334.
[10] Topological identification of the reaction type is used in a formal
sense to describe the number of atoms provided by each
fragment to the final cycloadduct, regardless of the mechanism
and the number of steps involved. The subscripts refer to the
corresponding reagent: C = carbene ligand (FCC), D = 1,3-
diene, E = enone/enal, S = substrate.
Angew. Chem. Int. Ed. 2007, 46, 4136 –4140
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