A Convenient Preparation of 3-Substituted Furans: Synthesis of Perillene and Dendrolasin

Article abstract of DOI:10.1021/ol025708s

(Matrix Presented) R= alkyl, allyl, propargyl, aryl A variety of 3-substituted furans, including the natural products perillene and dendrolasin, are obtained in good yield via reductive annulation of 1,1,1-trichloroethyl propargyl ethers using catalytic Cr(II) regenerated by Mn/TMSCI.

Full text of DOI:10.1021/ol025708s

ORGANIC
LETTERS
2
002
Vol. 4, No. 8
387-1389
A Convenient Preparation of
-Substituted Furans: Synthesis of
Perillene and Dendrolasin
1
3
†
†
‡
,‡,§
D. K. Barma, Abhijit Kundu, Rachid Baati, Charles Mioskowski,* and
J. R. Falck*
,†
Department of Biochemistry, UniVersity of Texas Southwestern Medical Center,
Dallas, Texas 75390-9038, and UniVersit e´ Louis Pasteur, Facult e´ de Pharmacie,
Laboratoire de Synth e` se Bio-Organique, associe au CNRS 67401 Illkirch, France
j.falck@utsouthwestern.edu
Received February 12, 2002
ABSTRACT
A variety of 3-substituted furans, including the natural products perillene and dendrolasin, are obtained in good yield via reductive annulation
of 1,1,1-trichloroethyl propargyl ethers using catalytic Cr(II) regenerated by Mn/TMSCl.
1
9
Furans are common subunits in pharmaceuticals, natural
organochromium reagents, we describe herein a convenient
2
3
4
products, fragrances, and flavors. They have also found
utility as synthetic intermediates or synthons for numerous
functional groups, inter alia, carboxylic acids, â-keto-esters,
and aromatics. While electrophilic aromatic substitution or
metalation of furans permit ready functionalization at C(2)/
synthesis of C(3)-substituted furan by reductive annulation
of 1,1,1-trichloroethyl propargyl ethers mediated by cata-
lytic Cr(II) coupled to a Mn/TMSCl regeneration system (eq
1
0
5
11
1).
6
(5), these methods are not generally applicable to the
preparation of C(3)-substituted furans. The latter are typically
7
obtained by elaboration of an existing C(3)-substituent or
8
accessed from acyclic precursors via multistep sequences.
In continuation of our exploration of the chemistry of
To study the efficacy of the annulation, a representative
panel of 1,1,1-trichloroalkynes was prepared by alkylation
of 2,2,2-trichloroethanol with various propargyl bromides at
†
University of Texas Southwestern.
Universit e´ Louis Pasteur.
E-mail: mioskow@aspirine.u-strasbg.fr.
‡
§
(
1) (a) Bock, I.; Bornowski, H.; Ranft, A.; Theis, H. Tetrahedron. 1990,
6, 1199-1210. (b) Mortensen, D. S.; Rodriguez, A. L.; Carlson, K. E.;
Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem.
4
(8) Review of furan syntheses: Hou, X. L.; Cheung, H. Y.; Hon, T. Y.;
Kwan, P. L.; Lo, T. H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998,
54, 1955-2020.
2
001, 44, 3838-3848.
(2) Murray, R. D. H. Aromat. Heteroaromat. Chem. 1978, 6, 258-281.
(3) Levisalles, J. Perfumery Essent. Oil Record 1958, 49, 627-635.
(4) Naim, M.; Zuker, I.; Zehavi, U.; Rouseff, R. L. J. Agric. Food Chem.
(9) Recent CrCl2-based methodology: (a) Falck, J. R.; Barma, D. K.;
Venkataraman, S. K.; Baati, R.; Mioskowski, C. Tetrahedron Lett. 2002,
43, 963-966. (b) Baati, R.; Barma, D. K.; Krishna, U. M.; Mioskowski,
C.; Falck, J. R. Tetrahedron Lett. 2002, 43, 959-961. (c) Baati, R.; Barma,
D. K.; Falck, J. R.; Mioskowski, C. J. Am. Chem. Soc. 2001, 123, 9196-
9197. (d) Barma, D. K.; Baati, R.; Valleix, A.; Mioskowski, C.; Falck, J.
R. Org. Lett. 2001, 3, 4237-4238. (e) Falck, J. R.; Barma, D. K.; Baati,
R.; Mioskowski, C. Angew. Chem., Int. Ed. 2001, 40, 1281-1283. (f) Baati,
R.; Valleix, A.; Mioskowski, C.; Barma, D. K.; Falck, J. R. Org. Lett. 2000,
2, 485-487. (g) Falck, J. R.; Barma, D. K.; Mioskowski, C.; Schlama, T.
Tetrahedron Lett. 1999, 40, 2091-2094.
1
993, 41, 1359-1361.
5) Meyers, A. I. Heterocycles in Organic Synthesis; Wiley-Inter-
science: New York, 1974.
(
(
6) (a) Kojima, Y.; Wakita, S.; Kato, N. Tetrahedron Lett. 1979, 4577-
4
4
580. (b) Tanis, S. P.; Herrinton, P. M. J. Org. Chem. 1983, 48, 4572-
580.
(7) Mandai, T.; Takeshita, M.; Mori, K.; Kawada, M.; Otera, J. Chem.
Lett. 1983, 1909-1910.
1
0.1021/ol025708s CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/19/2002

room temperature in the presence of NaOH/n-Bu
4
NI in
Stirring the structurally simplest of these, 1, with
stoichiometric (4-6 equiv) CrCl proved disappointing and
2
using catalytic CrCl . No olefin isomerization or reduction
1
2
CH
2
Cl
2
.
was observed during the transformation of styrene 7 to 8
(entry 4). Phenylacetylene 9, on the other hand, was
consumed under the standard catalytic conditions but af-
forded a poor yield (∼20%) of 10. However, the reaction
2
never generated more than a 30% yield of furan 2, regardless
of solvent or temperature, with the remaining material
balance being principally Z-chloroenol ether 30. In stark
contrast, 2 was obtained13 in good yield (Table 1, entry 1)
efficiency was significantly improved using 6 equiv of CrCl
2
at 60 °C for 12 h and furnished 10 in 70% yield (entry 5).
The presence of heteroatoms or leaving groups adjacent to
the distal side of the acetylene resulted in low yields, for
example, 11 to 12 (entry 6), although â-functionality was
well tolerated (13 to 14, entry 7). The reaction conditions
proved compatible with most other common functional
groups as well, inter alia, methyl ester 15, benzyl ether 17,
acetate 19, silyloxy 21, and free alcohol 23 which gave rise
to 3-substituted furans 16 (entry 8), 18 (entry 9), 20 (entry
Table 1. Synthesis of 3-Substituted Furans
1
0), 22 (entry 11), and 24 (entry 12), respectively. A
mechanistic interpretation of the preceding observations is
16
summarized in Scheme 1. One electron transfer from Cr(II)
Scheme 1
to the trichloroalkyne substrate with concomitant loss of
chloride spawns the key radical intermediate 25 which
1
7
undergoes cyclization to give vinylchromium 26 under
catalytic Cr(II) conditions (pathway a). Further transmeta-
lation and aromatization lead to furan 27. The latter was
2
inferred by quenching with D O, which resulted in 28,
incorporating one atom of deuterium. Alternatively, in the
presence of high concentrations of Cr(II), i.e., stoichiometric
conditions, reduction of 25 to 29 is competitive (pathway b)
and Z-chloroenol ether 30 is formed as previously described.9a
Control experiments demonstrated that both Mn and TMSCl
(
10) Multistep synthesis of 3-substituted furans using 1,1,1-trichloroethyl
allyl ethers: Ram, R. N.; Charles, I. Chem. Commun. 1999, 2267-2268.
11) CrCl2-based synthesis of 2,5-disubstituted furans: Takai, K.; Morita,
(
R.; Sakamoto, S. Synlett 2001, 1614-1616.
a
Six equivalents of CrCl2 at 60 °C for 12 h.
(12) Morimoto, T.; Sekiya, M. Synthesis 1981, 308-310.
(13) General procedure: 1,1,1-Trichloroethyl propargyl ether (1 mmol)
in THF (2 mL) is added to a stirring, room-temperature suspension of
anhydrous CrCl3 (15 mol %), Mn powder (4 mmol), and freshly distilled
TMSCl (4 mmol) in THF (8 mL) under argon. After complete addition,
the reaction mixture was heated at 60 °C. After 12-15 h, the reaction
mixture was cooled to ambient, quenched with an equal volume of water,
and extracted thrice with ether. The combined ethereal extracts were
evaporated in vacuo and the residue was purified by SiO2 chromatography
to give 3-substituted furans in the indicated yields (Table 1).
by warming a THF solution of 1 with a catalytic amount of
CrCl
TMSCl regeneration system as prescribed by F u¨ rstner.
Other solvents, e.g., HMPA, DMF, CH Cl , Et O, p-dioxane,
2 3
, or more conveniently CrCl , coupled to a Mn powder/
1
4
2
2
2
and EtOAc, were less satisfactory. Notably, the correspond-
ing tribromoethyl ether led to a complex product mixture
containing little, if any, 2.
Likewise, the naturally occurring15 furanyl terpenoids
perillene (4) and dendrolasin (6) were synthesized in a single
step from isoprenoids 3 and 5 (entries 2 and 3, respectively)
(
14) F u¨ rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 12349-12357.
(15) Bernardi, R.; Cardani, C.; Selva, D.; Baggini, A.; Pavan, M.
Tetrahedron Lett. 1967, 8, 3893-3896.
(
51.
16) Okazoe, T.; Takai, K.; Utimoto, K. J. Am. Chem. Soc. 1987, 109,
9
(17) Review of heterocyclic syntheses via radical cyclization: Bowman,
W. R.; Cloonan, M. O.; Krintel, S. L. J. Chem. Soc., Perkin Trans. 1 2001,
2885-29.
1388
Org. Lett., Vol. 4, No. 8, 2002

are need for the catalytic procedure to succeed. However,
the role of the TMSCl is obscure in this instance, but is not
a source of HCl as proposed11 in other systems since
exogenously added acid was detrimental to the yield.
In summary, we report a convenient, high-yield synthesis
of 3-substituted furans from readily available acyclic precur-
Acknowledgment. The authors thank Dr. E. R. Fogel for
helpful discussions. Financial support was provided by the
Robert A. Welch Foundation, the NIH (GM 31278, DK38226),
and the Instituts de Recherche Pierre Fabre, CNRS (to R.B.).
Supporting Information Available: Spectral data for all
new compounds. This material is available free of charge
via the Internet at http://pubs.asc.org.
2
sors utilizing, in most cases, catalytic CrCl . Extensions of
this methodology to the preparation of di- and trisubstituted
furans are under active investigation, and the results will be
the subject of future publications.
OL025708S
Org. Lett., Vol. 4, No. 8, 2002
1389