Silicon-assisted ring opening of donor-acceptor substituted cyclopropanes. An expedient entry to substituted dihydrofurans

Article abstract of DOI:10.1021/ol0163169

(Equation presented) (tert-Butyldiphenylsilyl)methylcyclopropanes undergo ring opening to furnish substituted dihydrofurans in good to excellent yields on treatment with TiCl₄ in dichoromethane. The silicon that assists the regioselective ring

Full text of DOI:10.1021/ol0163169

ORGANIC
LETTERS
2001
Vol. 3, No. 17
2717-2719
Silicon-Assisted Ring Opening of
Donor−Acceptor Substituted
Cyclopropanes. An Expedient Entry to
Substituted Dihydrofurans
Veejendra K. Yadav* and Rengarajan Balamurugan
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Vijendra@iitk.ac.in
Received June 21, 2001
ABSTRACT
(tert-Butyldiphenylsilyl)methylcyclopropanes undergo ring opening to furnish substituted dihydrofurans in good to excellent yields on treatment
with TiCl4 in dichoromethane. The silicon that assists the regioselective ring opening is retained in the product to allow further functional
group manipulations.
Cyclopropanes are useful synthetic intermediates because of
their ready accessibility and good reactivity. The silicon-
assisted ring opening of cyclopropane derivatives has been
utilized in the synthesis of substituted olefins.1 Vicinal
substitution of a donor and an acceptor on the cyclopropane
ring gives a sort of double activation and makes the ring
cleavage possible under mild conditions.2 The fluoride ion
and BF3-acetic acid systems have been used to cleave
cyclopropanes having a trimethylsilylmethyl group as the
donor substituent.3 The cleavage of the carbon-silicon bond
restricts the scope of this reaction, because an important
functionality is lost to allow further synthetic manipulations.
Hence, methods are required to effect ring opening without
the extrusion of the silicon. In doing so, the resulting ring-
opened species will have the features of a homo Michael
system and those of an enolate equivalent (Figure 1).
Figure 1.
The best way to achieve the above objective could be the
placement of bulky substituents on silicon, as these would
prevent the silicon from being attacked by nucleophiles,
which is the exclusive pathway in the allylsilane chemistry.4
In this report, we describe the TiCl4-assisted transformation
of such cyclopropylmethylsilanes having electron-attracting
groups into substituted dihydrofurans (Scheme 1).5 The
overall results are collected in Table 1.
tert-Butyldiphenylsilylmethyl-substituted cyclopropanes6
carrying different electron-attracting groups were treated with
TiCl4 under mild conditions.7 Cyclopropanes bearing two
(1) Ryu, I.; Hirai, A.; Suzuki, H.; Sonada, N.; Murai, S. J. Org. Chem.
1990, 55, 1409. Ryu, I.; Suzuki, H.; Murai, S.; Sonada, N. Organometallics
1987, 6, 212. Dubois, M. G.; Dunogues, J. J. Organomet. Chem. 1986,
309, 35. Dubois, M. G.; Calas, R. Can. J. Chem. 1981, 59, 802. Chan, T.
H.; Fleming, I. Synthesis 1979, 761. Dubois, M. G.; Pillot, J.-P.; Dunogues,
J.; Calas, R. J. Organomet. Chem. 1977, 124, 135.
(2) Reissig, H.-U. In Topics in Current Chemistry; de Meijere, A., Ed.;
Springer-Verlag: Berlin, Heidelberg, Germany, 1991; Vol. 144, pp 73-
135.
(3) Hirao, T.; Misu, D.; Agawa, T. J. Chem. Soc., Chem. Commun. 1986,
26. Reichelt, I.; Reissig, H.-U. Liebigs Ann. Chem. 1984, 828. Ochiai, M.;
Sumi, K.; Fujita, E. Chem. Pharm. Bull. 1983, 31, 3931. Ochiai, M.; Sumi,
K.; Fujita, E. Tetrahedron Lett. 1982, 23, 5419. Ochiai, M.; Sumi, K.; Fujita,
E. Chem. Lett. 1982, 79.
(4) Organ, M. G.; Dragan, V.; Miller, M.; Froese, R. D. J.; Goddard, J.
D. J. Org. Chem. 2000, 65, 3666 and references therein. For an excellent
review on the subject, see: Knolker, H.-J. J. Prakt. Chem. 1997, 339, 304.
10.1021/ol0163169 CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/02/2001

phenyl ketone. It is significant to note that the enolate did
not cyclize on the incipient carbocation to give the desired
dihydrofuran.
Scheme 1
The above methodology was extended to prepare bicyclic
ethers. The cyclopropane derived from 2-diazocyclohexane-
1,3-dione was so reactive that it furnished the desired product
under the conditions of its formation itself (Scheme 2). The
Scheme 2
electron-attracting groups (entries 1-4) underwent facile
regioselective ring opening to furnish substituted dihydro-
furans8 in good to excellent yields. A ketone enolate cyclized
use of a Lewis acid was not necessary. This high reactivity
may be attributed to the ring strain present in the spirobicycle.
The formation of the dihydrofuran proceeds presumably
through the 5-exo-trig cyclization of titanium enolate on the
silicon-stabilized carbocation10 that is formed from ring
opening (Scheme 3). The products of intermolecular addi-
tions were not observed.
Table 1. Transformation of the
(tert-butyldiphenylsilyl)methylcyclopropanes 3 into the
Dihydrofurans 4
entry silane
temp (°C)
time
3 h
3 h
10 min 4c
product
4a
4b
yield (%)a
1
2
3
4
5
3a
3b
3c
3d
-30
96
81
70
75
0 to room temp
-30
-30 to room temp 8 h
21 h
4d
Scheme 3 Mechanism of Dihydrofuran Formation
3eb 0 to room temp
no reaction
a
Isolated overall yield. b R1 ) H, R2 ) OEt.
in preference to an ester enolate (entry 3). This is in
accordance with the results observed in the copper-catalyzed
1,3-dipolar addition of diazomethylacetoacetate to electron-
rich olefins.9 No ring cleavage was observed, even at room
temperature, when the cyclopropane ring had a single ester
function (entry 5). This may be due to the insufficient
activation of the ring. In contrast, a single phenyl ketone
(2.4:1 mixture of isomers) brought about the ring cleavage
smoothly to furnish 3-hydroxy-4-tert-butyldiphenylsilylbutyl
In conclusion, cyclopropanes bearing electron-attracting
groups as the acceptor and the (tert-butyldiphenylsilyl)methyl
group as the donor are easily cleaved with TiCl4 to furnish
substituted dihydrofurans. The carbon-silicon bond is not
cleaved, and it is preserved in the product for its further
manipulation into useful functional groups, including OH.11
The reaction of the above enolate with electrophiles such as
aldehydes and ketones in an intermolecular process followed
by an intramolecular cyclization on the silicon-stabilized
carbocation to form substituted tetrahydrofuran rings is cur-
rently under investigation. The 1,4-addition of the in situ
generated enolate to enones, followed by cyclization of the
newly generated enolate onto the silicon-stabilized carboca-
tion, is likely to culminate in the synthesis of substituted
cyclopentanes. This aspect is also being investigated concur-
rently. The results of these and other studies will be reported
in due course.
(5) For alternate syntheses of dihydrofurans, see: Antonioletti, R.; Righi,
G.; Oliveri, L.; Bovicelli, P. Tetrahedron Lett. 2000, 41, 10127. Hwu, J. R.;
Chen, C. N.; Shiao, S.-S. J. Org. Chem. 1995, 60, 856. Abdallah, H.; Gree,
R.; Carrie, R. Tetrahedron 1985, 41, 4339. Also, see ref 9 of this paper.
(6) The substituted cyclopropylmethylsilanes were prepared conveniently
by a rhodium-catalyzed carbene insertion reaction of the corresponding diazo
compound with allyl-tert-butyldiphenylsilane. 3c, 3d, and 3e were respec-
tively 1.3:1, 1.4:1, and 1.7:1 mixtures of isomers.
(7) Typical Procedure: To a solution of the cyclopropylmethylsilane
3a (102 mg, 0.25 mmol) in dry CH2Cl2 (1.5 mL) was added a solution of
TiCl4 (57 mg, 0.3 mmol) in dry CH2Cl2 (1.5 mL) at -30 °C. The reaction
mixture was stirred for 3 h and then quenched with saturated aqueous NH4-
Cl solution. Et2O (10 mL) was added to it, and the layers were separated.
The aqueous layer was extracted with Et2O (2 × 5 mL). The combined
organic extracts were washed with water and brine and dried over anhydrous
Na2SO4. Removal of the solvents under reduced pressure furnished the crude
product, which was purified by column chromatography (EtOAc/hexanes)
to isolate 4a; yield 98 mg, 96%.
(8) The structures of 4b and 4c were confirmed by comparing the spectral
data available for similar known compounds reported in ref 5. The structures
of 4a and 4d were confirmed by transforming them into 5-((tert-
butyldiphenylsilyl)methyl)-γ-lactone by acid hydrolysis followed by dealkyl-
decarboxylation and desulfonation, respectively.
(9) Alonso, M. E.; Morales, A.; Chitty, A. W. J. Org. Chem. 1982, 47,
3747. Wenkert, E.; Alonso, M. E.; Buckwalter, B. L.; Sanchez, E. L. J.
Am. Chem. Soc. 1983, 105, 2021.
(10) For discussions on silyl-stabilized â-carbocations, see: Fleming, I.
Frontier Orbitals and Organic Chemical Reactions; Wiley: London, 1976;
p 81. Wierschke, S. G.; Chandrasekhar, J.; Jorgensen, W. L. J. Am. Chem.
Soc. 1985, 107, 1496. Lambert, J. B.; Wang, G.-T.; Finzel, R. B.; Teramura,
D. H. J. Am. Chem. Soc. 1987, 109, 7838. Lambert, J. B. Tetrahedron 1990,
46, 2677. Lambert, J. B.; Chelius, E. C. J. Am. Chem. Soc. 1990, 112,
8120. Green, A. J.; Kuan, Y.-L.; White, J. M. J. Org. Chem. 1995, 60,
2734. Gabelica, V.; Kresge, A. J. J. Am. Chem. Soc. 1996, 118, 3838. Chan,
V. Y.; Clark, C. I.; Giordano, J.; Green, A. J.; Karalis, A.; White, J. M. J.
Org. Chem. 1996, 61, 5227.
(11) Knolker, H.-J.; Jones, P. G.; Wanzl, G. Synlett 1998, 613.
2718
Org. Lett., Vol. 3, No. 17, 2001

Acknowledgment. We thank the DST, Government of
India, for financial assistance, the UGC, Government of
India, for a Senior Research Fellowship to R.B., and
Professor H. Junjappa for fruitful discussions.
Supporting Information Available: Experimental details.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL0163169
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