Efficient synthesis of substituted 2-silylfurans from acylsilane dicarbonyl compounds

Full text of DOI:10.1021/jo9514432

1140
J . Org. Chem. 1996, 61, 1140-1142
Ta ble 1. 2-Silylfu r a n s fr om Acylsila n e Dica r bon yl
Com p ou n d s
Efficien t Syn th esis of Su bstitu ted
2-Silylfu r a n s fr om Acylsila n e Dica r bon yl
Com p ou n d s
acysilane
silylfuran
R1
R2
R3
% isoltd yielda
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
H
H
H
H
H
Me
H
H
H
H
H
Me
Ph
H
75
87
65
57
81
Christopher S. Siedem† and Gary A. Molander*
Department of Chemistry and Biochemistry, University of
Colorado, Boulder, Colorado 80309-0215
Me
a
Refers to yields of purified product after Kugelrohr distillation.
All of the above compounds have been fully characterized spec-
troscopically (1H NMR, 13C NMR, IR), and elemental composition
has been established by combustion analysis and/or exact mass.
Received August 4, 1995
Furans1 have enjoyed an important niche in organic
synthesis as a result of their frequent occurrence in
natural products2 as well as their role as versatile
synthetic intermediates in a wide variety of organic
transformations.3 Because of their importance, there
exists a need for efficient methods of furan synthesis that
control the regiochemistry of substituents placed about
the ring.4 Traditional methods have relied upon the acid-
catalyzed dehydrative cyclization of 1,4-dicarbonyl com-
pounds5 or further elaboration of an existing furan
nucleus.6 Herein, we report a route to substituted
2-silylfurans 2 from acylsilane dicarbonyl compounds 1
that introduces synthetic flexibility to the more tradi-
tional dicarbonyl entry to furans (Scheme 1).
The synthesis of the requisite acylsilane dicarbonyl
compounds 1 was accomplished by the coupling of 2-silyl-
1,3-dithianes with halo acetals (Scheme 2). The details
of these syntheses have previously been disclosed.7
While we were investigating the chemistry of 1 in
Lewis acid-promoted [3 + 4] and [3 + 5] annulation
reactions with bis(trimethylsilyl) enol ethers,7,8 the in-
stability of these dicarbonyl substrates toward both Lewis
acids and protic acids became readily apparent. Annu-
lation of 1 with the bis(trimethylsilyl) enol ether of
methyl acetoacetate in the presence of catalytic trimeth-
ylsilyl triflate was sometimes contaminated by as much
as 20-40% of the furan (eq 1). In fact, some furan was
formed during the purification of 1 by flash chromatog-
raphy on silica gel or upon allowing 1 to stand for several
days at room temperature.
† Current address: Ariad Pharmaceuticals, Inc., 26 Landsdowne St.,
Cambridge, MA 02139-4234.
(1) For general reviews on the chemistry of furans: (a) Bosshard,
P.; Eugster, C. H. In Advances in Heterocyclic Chemistry; Katritzky,
A. R., Boulton, A. J ., Eds.; Academic Press: New York, 1966; Vol. 7,
pp 377-490. (b) Dean, F. M. In Advances in Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Academic Press: New York, 1982; Vol. 30, pp
167-238. (c) Dean, F. M. In Advances in Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Academic Press: New York, 1982; Vol. 31, pp
237-344. (d) Dean, F. M.; Sargent, M. V. In Comprehensive Heterocyclic
Chemistry; Bird, C. W., Cheeseman, G. W. H., Eds.; Pergamon Press:
New York, 1984; Vol. 4, Part 3, pp 531-598. (e) Dean, F. M. In
Comprehensive Heterocyclic Chemistry; Bird, C. W., Cheeseman, G. W.
H., Eds.; Pergamon Press: New York, 1984; Vol. 4, Part 3, pp 599-
656. (f) Donnelly, D. M. X.; Megan, M. J . In Comprehensive Heterocyclic
Chemistry; Bird, C. W., Cheeseman, G. W. H., Eds.; Pergamon Press:
New York, 1984; Vol. 4, Part 3, pp 657-712. (g) Sargent, M. V.; Cresp,
T. M. In Comprehensive Organic Chemistry; Barton, D. H. R., Ollis,
W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, pp 693-744.
(2) (a) J acobi, P. A. In Advanced Heterocyclic Natural Product
Synthesis; Pearson, W. H., Ed.; J AI Press: London, 1992; Vol. 2, p
251. (b) Glasby, J . S. Encyclopedia of the Terpenoids; Wiley: New York,
1982. (c) Fenical, W.; Okuda, R. K.; Bandurraga, M. M.; Clulver, P.;
J acobs, R. S. Science 1981, 212, 1512. (d) Bandurraga, M. M.; Fenical,
W.; Donovan, S. F.; Clardy, J . J . Am. Chem. Soc. 1982, 104, 6463. (e)
Wright, A. E.; Burres, N. S.; Schulte, G. K. Tetrahedron Lett. 1989,
30, 3491. (f) Paterson, I.; Gardner, M.; Banks, B. J . Tetrahedron 1989,
45, 5283.
(3) (a) Lipshutz, B. H. Chem. Rev. 1986, 86, 795. (b) Tanis, S. P.;
Herrinton, P. M. J . Org. Chem. 1985, 50, 3988. (c) Martin, S. F., Zinke,
P. W. J . Am. Chem. Soc. 1989, 111, 2311. (d) Martin, S. F., Guinn, D.
E. J . Org. Chem. 1987, 52, 5588. (e) Piancatelli, G. Heterocycles 1985,
23, 667. (f) Piancatelli, G. Heterocycles 1982, 19, 1735. (g) Antonioletti,
R.; Bonadies, F.; Prencipe, T.; Scettri, A. Gazz. Chem. Ital. 1988, 118,
629. (h) Kusakabe, M.; Sato, F. J . Org. Chem. 1989, 54, 3486.
(4) (a) Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H. J . Am.
Chem. Soc. 1991, 113, 5816. (b) Srikrishna, A.; Sundarababu, G.
Tetrahedron 1990, 46, 7901. (c) Danheiser, R. L.; Stoner, E. J .; Koyama,
H.; Yamashita, D. S.; Klade, C. A. J . Am. Chem. Soc. 1989, 111, 4407.
(d) Padwa, A.; Murphree, S. S.; Yeske, P. E. J . Org. Chem. 1990, 55,
4241. (e) Marshall, J . A.; Wang, X.-J . J . Am. Chem. Soc. 1991, 113,
960. (f) McCombie, S. W.; Shankar, B. B.; Ganguly, A. K. Tetrahedron
Lett. 1987, 28, 4123. (g) Hiroi, K.; Sato, H. Synthesis 1987, 811. (h)
Davies, H. M. L.; Romines, K. R. Tetrahedron 1988, 44, 3343. (i)
Marshall, J . A.; Wang, X. J . Org. Chem. 1991, 56, 960. (j) Marshall, J .
A.; Bennett, C. E. J . Org. Chem. 1994, 59, 6110. (k) Marshall, J . A.;
Bartley, G. S. J . Org. Chem. 1994, 59, 7169.
The ready formation of silylfurans from 1 can be
attributed to the greater relative contribution of reso-
nance form 1B in the acylsilanes when compared to alkyl
ketones.9 Resonance form 1B is stabilized by the induc-
tive release of electron density from the silicon atom
toward the carbonyl group. This results in an increase
in nucleophilicity at the acylsilane carbonyl oxygen.10
Intramolecular attack of this oxygen on the alkyl ketone
with subsequent loss of water from the intermediate
accounts for the formation of the furan.
This reactivity pattern of acylsilanes is used to advan-
tage in the preparation of substituted 2-silylfurans 2 from
acylsilane dicarbonyl compounds 1 (Table 1).
In all cases, the 2-silylfurans 2 were readily obtained
in good to excellent yields under mild conditions. The
yields of furans 2c and 2d are lowered slightly because
of unfavorable steric interactions that develop upon ring
formation and elimination of water in the 2,3-disubsti-
tuted furans. For these more highly substituted systems
(7) Molander, G. A.; Siedem, C. S. J . Org. Chem. 1995, 60, 130.
(8) (a) Molander, G. A.; Cameron, K. O. J . Org. Chem. 1993 58, 5931.
(b) Molander, G. A.; Cameron, K. O. J . Am. Chem. Soc. 1993, 115, 830.
(c) Molander, G. A.; Cameron, K. O. J . Org. Chem. 1991 56, 2617. (d)
Molander, G. A.; Carey, J . C. J . Org. Chem. 1995, 60, 4559. (e)
Molander, G. A.; Eastwood, P. R., J . Org. Chem. 1995, 60, 4845. (f)
Molander, G. A.; Eastwood, P. R. J . Org. Chem., in press.
(5) (a) Perumal, P. T.; Balsundaram, B. Venugopal, M Synth.
Commun. 1993, 23, 2593. (b) Duhamel, L.; Chauvin, J . Chem. Lett.
1985, 693.
(6) (a) Goldfarb, J . L.; Volkenstein, J . B.; Belenkij, J . I. Angew.
Chem., Int. Ed. Engl. 1968, 7, 519. (b) Haarmann, H.; Eberbach, W.
Tetrahedron Lett. 1991, 32, 903. (c) Keay, B. A.; Bures, E. J .
Tetrahedron Lett. 1988, 29, 1247. (d) Katsumura, S.; Ichikawa, K.;
Mori, H. Chem. Lett. 1993, 1525. (e) Beese, G.; Keay, B. A. Synlett
1991, 33.
(9) For recent reviews of acylsilane chemistry: (a) Panek, J . S.;
Cirillo, P. F. Org. Prep. Proc. Int. 1992, 24, 555. (b) Bulman Page, P.
C.; Klair, S. S.; Rosenthal, S. Chem. Soc. Rev. 1990, 19, 147. (c) Ricci,
A.; Degl’Innocenti, A. Synthesis 1989, 647.
(10) (a) Tsai, Y.-M.; Nieh, H.-C.; Cherng, C.-D. J . Org. Chem. 1992,
57, 7010. (b) Yates, K.; Agolini, F. Can. J . Chem. 1966, 44, 2229.
0022-3263/96/1961-1140$12.00/0 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 3, 1996 1141
Sch em e 1
Sch em e 2
Gen er a l P r oced u r e for th e Syn th esis of 2-Silylfu r a n s
fr om Acylsila n e Dica r bon yl Com p ou n d s. A stirred solution
of acylsilane dicarbonyl compound (50-100 mg) in THF (3 mL)
and 1 N HCl (1 mL) was stirred at room temperature for 4-24
h. The mixture was diluted with ether, washed with saturated
aqueous NaHCO3 and brine, dried (K2CO3), and concentrated
in vacuo. Flash chromatography of the residue on silica gel (1%
ether in hexanes) followed by Kugelrohr distillation provided
the silylfuran.
it was beneficial to use a two-step protocol for furan
formation. For example, brief exposure of 1d to aqueous
acid caused rapid intramolecular cyclization. Subsequent
treatment of the crude hemiacetal with methanesulfonyl
chloride and pyridine at 0 °C provided furan 2d in 69%
yield (eq 2).
2-(Meth yld ip h en ylsilyl)fu r a n (2a ). 2a was isolated in 75%
yield from (1,4-dioxobutyl)methyldiphenylsilane (1a ) after 16
1
h: oven temperature (ot) 90-100 °C/0.2 mmHg; H NMR (400
MHz, CDCl3) δ 7.80 (d, J ) 1.6 Hz, 1H), 7.64 (m, 4H), 7.48-
7.41 (m, 6H), 6.79 (d, J ) 3.2 Hz, 1H), 6.48 (dd, J ) 3.2, 1.6 Hz,
1H), 0.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.36, 147.70,
134.98, 134.92, 129.65, 127.89, 122.87, 109.52, -3.99; IR (neat)
3069 cm-1; LRMS (EI+) m/ z 264 (52), 249 (100), 223 (8), 187
(8), 171 (8), 105 (25), 53 (6). Anal. Calcd for C17H26OSi: C,
77.21; H, 6.11. Found: C, 76.90; H, 6.09.
It is noteworthy that furans 2 could also be prepared
directly from the protected dithiane acetal 3 without
isolation of the acylsilane dicarbonyl compound by em-
ploying a one-pot hydrolysis/cyclization sequence. For
example, when 3b was treated with HgCl2 in unbuffered
medium, furan 2b was isolated in 71% yield (eq 3).
Unfortunately, this one-pot operation could not be ex-
tended to furans 2c and 2d , which possess the 2,3-
disubstituted furan substitution pattern.
4-Meth yl-2-(m eth yld ip h en ylsilyl)fu r a n (2b). 2b was iso-
lated in 87% yield from (3-methyl-1,4-dioxobutyl)methyldiphe-
1
nylsilane (1b) after 16 h: ot 100 °C/0.03 mmHg; H NMR (400
MHz, CDCl3) δ 7.62 (m, 4H), 7.53 (s, 1H), 7.47-7.38 (m, 6H),
6.61 (s, 1H), 2.08 (s, 3H), 0.85 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 156.46, 144.70, 135.13, 134.92, 129.60, 127.88, 125.70,
119.82, 9.33, -4.00; IR (neat) 3069, 1428, 1252, 1113, 1078, 912,
791, 676, 599 cm-1; HRMS calcd for C18H18OSi 278.1127, found
278.1118; LRMS (EI+) m/ z 278 (82), 263 (100), 223 (18), 197
(16), 161 (14), 145 (15), 105 (45), 91 (11), 77 (13), 53 (19), 39
(16).
4-Meth yl-2-(m eth yld ip h en ylsilyl)fu r a n (2b) fr om [2-[2-
(1,3-d ioxola n -2-yl)-1-m eth yleth yl]-1,3-d ith ia n -2-yl]m eth yl-
d ip h en ylsila n e (3b). A solution of [2-[2-(1,3-dioxolan-2-yl)-1-
methylethyl]-1,3-dithian-2-yl]methyldiphenylsilane (3b ) (130
mg, 0.302 mmol) and mercuric chloride (456 mg, 1.68 mmol) in
90% acetone (10 mL) was stirred at room temperature for 24 h.
HCl (6N, 1 drop) was added, and stirring was continued for 2 h.
The mixture was diluted with ether, filtered through Celite/
neutral alumina, washed with water and brine, dried (K2CO3),
and concentrated in vacuo. Flash chromatography of the residue
on silica gel (petroleum ether) provided furan 2b (60 mg, 71%),
which was identical to material prepared above.
The method developed herein should find use in
organic synthesis. It represents an improvement over
the traditional dicarbonyl cyclization routes to furans in
that the acylsilane undergoes reaction under milder
reaction conditions and, in general, gives more acceptable
yields than simple alkyl-substituted 1,4-diketones. Fur-
thermore, the silyl substituent facilitates the subsequent
regiospecific C2-elaboration of the furan ring by either
electrophilic substitution or metalation-addition strate-
gies.11
3-Meth yl-2-(m eth yld ip h en ylsilyl)fu r a n (2c). 2c was iso-
lated in 65% yield from (2-methyl-1,4-dioxobutyl)methyldiphe-
nylsilane (1c) (100 mg, 0.338 mmol) in THF (5 mL) and 1 N
HCl (3 drops) for 24 h: ot 110 °C/0.1mmHg; 1H NMR (400 MHz,
CDCl3) δ 7.64 (d, J ) 1.2 Hz, 1H), 7.59 (dd, J ) 7.7, 1.4 Hz, 4H),
7.46-7.38 (m, 6H), 6.31 (d, J ) 1.2 Hz, 1H), 1.90 (s, 3H), 0.87
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.53, 146.91, 135.40,
135.01, 133.07, 129.54, 127.88, 112.98, 11.27, -3.28; IR (neat)
3069 cm-1; LRMS (EI+) m/ z 278 (21), 263 (34), 185 (10), 161
(5), 141 (10), 105 (21), 84 (100), 77 (10), 47 (55). Anal. Calcd
for C18H18OSi: C, 77.63; H, 6.52. Found. C, 77.23; H, 6.65.
2-(Meth yld ip h en ylsilyl)-3-p h en ylfu r a n (2d ). 2d was Iso-
lated in 57% yield from (1,4-dioxo-2-phenylbutyl)methyldiphe-
Exp er im en ta l Section
Rea gen ts. Tetrahydrofuran (THF) was distilled immediately
prior to use from benzophenone ketyl under Ar. CH2Cl2 was
stirred over sulfuric acid, decanted, and stirred over K2CO3. It
was distilled from CaH2 onto 4 Å molecular sieves and stored
over 4 Å molecular sieves. Standard benchtop techniques were
employed for handling air-sensititve reagents,12 and all reactions
were carried out under argon.
1
nylsilane (1d ) after 16 h: ot 115 °C/0.15 mmHg; H NMR (400
(11) (a) Nakayama, K.; Harigaya, Y.; Okomoto, H.; Tanaka, A. J .
Heterocycl. Chem. 1991, 28, 853. (b) Nakayama, K.; Tanaka, A. Chem.
Expr. 1991, 6, 699. (c) Gill, M. Tetrahedron 1984, 40, 621.
(12) Brown, H. C. Organic Syntheses via Boranes; Wiley: New York,
1975.

1142 J . Org. Chem., Vol. 61, No. 3, 1996
Notes
MHz, CDCl3) δ 7.70 (d, J ) 1.5 Hz, 1H), 7.48 (m, 4H), 7.37-
7.27 (m, 6H), 7.18-7.12 (m, 5H), 6.56 (d, J ) 1.5 Hz, 1H), 0.60
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 151.17, 147.26, 139.56,
135.34, 135.04, 134.16, 133.98, 129.48, 128.80, 127.86, 127.80,
127.72, 126.95, 111.91, -3.70; IR (neat) 3068, 1558, 1503, 1428,
1373, 1254, 1111, 1048, 790, 754, 726, 697, 668 cm-1; HRMS
calcd for C23H20OSi 340.1278, found 340.1283; LRMS (EI+) m/ z
340 (94), 325 (100), 247 (34), 223 (20), 197 (10), 165 (9), 105 (23),
77 (9), 51 (5).
Alter n a te P r oced u r e for 2d . To a stirred solution of 1d
(70 mg, 0.19 mmol) in THF (10 mL) at room temperature was
added 1 N HCl (1 drop), and stirring was continued for 10 min.
The mixture was dried (MgSO4) and concentrated in vacuo to
provide crude 4,5-dihydro-2-hydroxy-5-(methyldiphenylsilyl)-4-
phenylfuran (4d ): 1H NMR (400 MHz, CDCl3) δ 7.58 (dt, J )
1.5 8.0, 1.4 Hz, 4H), 7.39-7.30 (m, 6H), 7.09 (m, 5H), 5.88 (m,
1H), 3.32 (dd, J ) 16.9, 6.8 Hz, 1H), 2.98 (d, J ) 4.2 Hz, 1H),
2.87 (dd, J ) 16.9, 2.0 Hz, 1H), 0.52 (s, 3H). To a stirred solution
of crude 4d in dichloromethane (5 mL) cooled to 0 °C were added
methanesulfonyl chloride (75 µL, 0.969 mmol) and pyridine (160
µL, 1.98 mmol), and stirring was continued for 1 h at 0 °C. The
solution was washed with water and then brine, dried over
MgSO4, and concetrated in vacuo. Flash chromatography of the
residue on silica gel (1% ether in hexanes) provided 2d (46 mg,
69%), which was identical to the material prepared above.
5-Meth yl-2-(m eth yld ip h en ylsily)fu r a n (2e). 2e was iso-
lated in 81% yield from (1,4-dioxopentyl)methyldiphenylsilane
(1e) after 4 h: ot 100 °C/0.1 mmHg; 1H NMR (400 MHz, CDCl3)
δ 7.59 (m, 4H), 7.44-7.36 (m, 6H), 6.61 (d, J ) 3.0 Hz, 1H), 6.02
(d, J ) 3.0 Hz, 1H), 2.36 (s, 3H), 0.80 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 157.78, 154.34, 135.40, 134.95, 1229.52, 127.83,
124.27, 105.94, 13.85, -3.91; IR (neat) 3069, 1490, 1428, 1252,
1215, 1187, 1114, 1018, 956, 787, 726, 698 cm-1; LRMS (EI+)
m/ z 278 (70), 263 (100), 237 (7), 201 (10), 185 (9), 161 (7), 141
(5), 105 (20), 77 (5), 43 (12). Anal. Calcd for C18H18OSi: C,
77.65; H, 6.52. Found: C, 77.60; H, 6.34.
Ack n ow led gm en t. This work was carried out with
generous support from the National Institutes of Health.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds for which no elemental analysis was
obtained (5 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of this journal, and can be ordered from the ACS; see
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J O9514432