A telluride-triggered nucleophilic ring opening of monoactivated cyclopropanes

Article abstract of DOI:10.1021/ol0492804

Acylcyclopropanemethanol tosylates undergo rapid ring opening at room temperature by the action of lithium telluride to produce the enolate of a homoallylic ketone. The enolate can be protonated to yield the corresponding ketone or treated with benzaldehy

Full text of DOI:10.1021/ol0492804

ORGANIC
LETTERS
2004
Vol. 6, No. 13
2225-2228
A Telluride-Triggered Nucleophilic Ring
Opening of Monoactivated
Cyclopropanes1
Dmitry V. Avilov, Mahesh G. Malusare, Engin Arslancan, and Donald C. Dittmer*
Department of Chemistry, 1-014 Center for Science and Technology,
Syracuse UniVersity, Syracuse, New York 13244
dcdittme@syr.edu
Received April 19, 2004
ABSTRACT
Acylcyclopropanemethanol tosylates undergo rapid ring opening at room temperature by the action of lithium telluride to produce the enolate
of a homoallylic ketone. The enolate can be protonated to yield the corresponding ketone or treated with benzaldehyde to give the aldol
product with good syn or anti diastereoselectivity depending on the conditions.
The synthetically useful nucleophilic ring openings of
cyclopropanes activated by substitution with electron-
withdrawing groups have been investigated extensively since
the discovery by Perkin and Bone.2,3 While both inter- and
intramolecular nucleophilic reactions of diactivated cyclo-
propanes are common,3,4 those of monoactivated rings are
somewhat rarer, often requiring either a very strong
nucleophile,5-10 electrophilic (Lewis acid) catalysis (carbo-
cations are likely to be involved),11-14 the involvement of
strain or spiroconjugation,7,15 or a facile, intramolecular
process.14,16 Unactivated cyclopropylmethyllithium species
undergo ring opening to allylic alkyllithium intermediates
that are trapped by reaction with electrophiles.17
(9) Cuprates: (a) Casey, C. P.; Cesa, M. C. J. Am. Chem. Soc. 1979,
101, 4236-4244. (b) Frejaville, C.; Jullien, R. Tetrahedron Lett. 1971, 12,
2039-2041.
(10) Trimethylsilyl anion: Hwu, J. R. J. Chem. Soc., Chem. Commun.
1985, 452-453.
(1) Preliminary report: Dittmer, D. C.; Malusare, M. G.; Arslancan, E.
Abstracts of Papers, 225th National Meeting of the American Chemical
Society, New Orleans, LA; American Chemical Society: Washington, DC,
2003; ORGN 703.
(11) p-Toluenesulfonic acid: (a) Lim, Y.-H.; McGee, K. F., Jr.; Sieburth,
S. McN. J. Org. Chem. 2002, 67, 6535-6538. (b) Yates, P.; Helferty, H.;
Mahier, P. Can. J. Chem. 1983, 61, 78-85.
(12) Acetylmethanesulfonate: Demuth, M.; Raghavan, P. R. HelV. Chim.
Acta 1979, 62, 2338-2340.
(2) Bone, W. A.; Perkin, W. H., Jr. J. Chem. Soc. 1895, 67, 108-119.
(3) Reviews of nucleophilic ring openings of cyclopropanes: (a) von
Angerer, S. In Methods Of Organic Chemistry (Houben-Weyl); de Meijere,
A., Ed.; George Thieme: Stuttgart, 1997; Vol. E17c, pp 2082-2120 and
2140-2152. (b) Verhe´, R.; De Kimpe, N. In The Chemistry of the
Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987; Vol. 1,
pp 517-564. (c) Danishefsky, S. Acc. Chem. Res. 1979, 12, 66-72. (d)
Reissig, H.-U.; Zimmer, R. Chem. ReV. 2003, 103, 1151-1196.
(4) For an intramolecular example: Danishefsky, S.; Dynak, J.; Hatch,
E.; Yamamoto, M. J. Am. Chem. Soc. 1974, 96, 1256-1259.
(5) Thiophenoxide: Truce, W. E.; Lindy, L. B. J. Org. Chem. 1961, 27,
1463-1467.
(13) Trimethylsilyl cation equivalents: (a) Brown, S. P.; Balkrishna, S.
B.; Pinnick, H. W. Tetrahedron Lett. 1981, 22, 4891-4894. (b) Dieter, R.
K.; Pounds, S. J. Org. Chem. 1982, 47, 3174-3177 (also aluminum
chloride).
(14) Titanium tetrachloride: Yadav, V. K.; Balamurugan, R. Org. Lett.
2003, 5, 4281-4284.
(15) (a) Meinwald, J.; Crandall, J. K. J. Am. Chem. Soc. 1966, 88, 1292-
1301. (b) Buss, P.; Prewo, R.; Bieri, J. H.; Ru¨edi, P. HelV. Chim. Acta,
1986, 69, 456-466. (c) The ring-opening of 1,1-(bromomethyl)cyclopropane
via triphenylphosphine may involve strain induced by the geminal groups:
Zefirov, N. S.; Kuznetsova, T. S.; Kozhushkov, S. I.; Potekhin, K. A.;
Maleev, A. V.; Struchkov, Yu. T. J. Org. Chem. USSR 1988, 10, 1874-
1877.
(6) Phenylselenolates: Smith, A. B., III; Scarborough, R. M., Jr.
Tetrahedron Lett. 1978, 19, 1649-1652.
(7) Porphyrinatorhodium(I) anion: Ogoshi, H.; Setsune, J.-I.; Yoshida,
Z.-I. J. Organomet. Chem. 1980, 185, 95-104.
(16) Tomazic, A.; Ghera, E. Tetrahedron Lett. 1981, 22, 4249-4252.
(17) (a) Cram, D. J. Fundamentals of Carbanion Chemistry; Academic
Press: New York, 1965; pp 211-222. (b) Charette, A. B.; Naud, J.
Tetrahedron Lett. 1998, 39, 7259-7262 and references therein.
(8) “Supernucleophilic” vitamin B12: Ogoshi, H.; Kikuchi, Y.; Yamagu-
chi, T.; Toi, H.; Aoyama, Y. Organometallics 1987, 6, 2175-2178.
10.1021/ol0492804 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/05/2004

Tellurium-triggered rupture of the three-membered rings
of chloromethyloxiranes,18 mesylates or tosylates of oxi-
ranemethanols,19 and aziridinemethanols20 and a related
reaction of 5-hydroxymethyl-2-oxazolidinone derivatives21
provide syntheses of allylic alcohols and amines (Scheme
1). These reactions exemplify the use of nontoxic22 elemental
Table 1. Nucleophilic Reduction of Cyclopropanemethanol
Tosylates by Lithium Telluridea
Scheme 1. Allylic Alcohols and Amines by Telluride-Induced
Nucleophilic Reduction
tellurium to create the equivalent of a nucleophilic carbanion
exocyclic to an oxirane, aziridine, or oxazolidinone ring
without the requirement of a silicon or organolithium
exocyclic functional group. A bonus is the recovery and reuse
of the key tellurium reagent.
We reasoned that this process, designated “nucleophilic
reduction”,19c could also be applied to cyclopropanemethanol
derivatives. In fact, nucleophilic ring-opening of a cyclo-
propane ring was observed upon treatment of the p-
toluenesulfonate of 1-[2-(hydroxymethyl)cyclopropyl]-2,2-
dimethyl-1-propanone (2a) and related compounds with
lithium telluride, prepared by reduction of tellurium powder
with lithium triethylborohydride,23 to give the enolates of
homoallylic ketones 3a-d (Scheme 2, Table 1).
Scheme 2. Nucleophilic Reduction of 2a-d with Telluride
Ion
a All reactions were performed at room temperature on a 0.5 mmol scale
with the use of 1.1 equiv of lithium telluride. b Isolated yields unless
otherwise noted. All yields are based on the alcohols 1a-f. See Supporting
Information for details. c Yield determined by GC-MS analysis of the crude
reaction mixture. d As evidenced by the 1H NMR spectrum of the crude
reaction mixture.
LDA) or, as with silylmethylcyclopropyl ketones, an elec-
trophile such as titanium tetrachloride.14 The byproducts
are elemental tellurium (reusable) and lithium tosylate.
Enolates have been obtained also from R-halocarbonyl
compounds and various tellurides;24 the acylcyclopropane-
methanol tosylates 2a-d may be considered as “cyclo-
propanalogues”,25 similar to vinylogues of R-haloketones in
which the carbon-carbon double bond (C2H2) of a vinylog
is replaced by the cyclopropane ring (C3H4).
This telluride-triggered generation of enolates of alkyl or
aryl 3-butenyl ketones does not require a strong base (e.g.,
(18) Polson, G.; Dittmer, D. C. Tetrahedron Lett. 1986, 27, 5579-5582.
(19) (a) Discordia, R. P.; Dittmer, D. C. J. Org. Chem. 1990, 55, 1414-
1415. (b) Discordia, R. P.; Murphy, C. K.; Dittmer, D. C. Tetrahedron
Lett. 1990, 31, 5603-5606. (c) Dittmer, D. C.; Discordia, R. P.; Zhang,
Y.; Murphy, C. K.; Kumar, A.; Pepito, A. S.; Wang, Y. J. Org. Chem.
1993, 58, 718-731. (d) Xu, Q.; Chao, B.; Wang, Y.; Dittmer, D. C.
Tetrahedron 1997, 53, 12131-12146. (e) Kumar, A.; Dittmer, D. C.
Tetrahedron Lett. 1994, 35, 5583-5586. (f) Chao, B.; Dittmer, D. C.
Tetrahedron Lett. 2000, 41, 6001-6004. (g) Kumar, A.; Dittmer, D. C. J.
Org. Chem. 1994, 59, 4760-4764. (h) Pepito, A. S.; Dittmer, D. C. J. Org.
Chem. 1994, 59, 4311-4312.
(22) (a) U.S. Federal Register, Rules and Regulations. Environmental
Protection Agency, 1996, 61, 20473-20490. (b) Lewis, R. J., Sr. Sax’s
Dangerous Properties of Industrial Material; John Wiley: New York, 2000;
3, 3353-3354.
(23) (a) Gladysz, J. A.; Hornby, J. L.; Garbe, J. E. J. Org. Chem. 1978,
43, 1204-1208. (b) Clive, D. L. Y.; Anderson, P. C.; Moss, N.; Singh, A.
J. Org. Chem. 1982, 47, 1641-1647.
(20) (a) Pepito, A. S.; Dittmer, D. C. J. Org. Chem. 1997, 62, 7920-
7925. (b) Chao, B.; Dittmer, D. C. Tetrahedron Lett. 2001, 42, 5789-
5791.
(21) Xu, Q.; Dittmer, D. C. Tetrahedron Lett. 1999, 40, 2255-2258.
2226
Org. Lett., Vol. 6, No. 13, 2004

The spirocyclopentadienyl derivative 2e (Table 1, entry
group by telluride ion to give the monoalkyltelluride ion 8
(which in the case of 2f leads to telluride 7). Then, 8
undergoes intramolecular nucleophilic attack on the cyclo-
propane ring to give the unstable epitelluride intermediate
9, which readily eliminates elemental tellurium to form
enolate 10, which is protonated during workup (Scheme 3).
5) underwent ring opening to give a mixture of 1- and 2-allyl-
1
1,3-cyclopentadienes 5a,b.26 The 600 MHz H NMR spec-
trum of the mixture allowed sufficient separation of the
chemical shifts of the two isomers for determination of the
isomer ratio of about 60:40 in favor of 2-allylcyclopenta-
diene.26 The facile ring-opening of the spirocyclopentadiene
is attributed to the stability of the cyclopentadienyl anion.
The reaction of (2-phenylcyclopropyl)methanol tosylate 2f
with telluride ion is different, yielding mainly unstable
telluride 7 (84%) with perhaps a trace of the ring-opened
product, 3-butenylbenzene 6 (Table 1, entry 6). The forma-
tion of a relatively less stable benzyl anion apparently is not
favored.
Scheme 3. Mechanism for the Telluride-Triggered
Nucleophilic Ring Opening of Cyclopropanes
The use of other reducing agents for tellurium gave lower
yields of 3a and often required longer reaction times: sodium
borohydride-water-benzene phase transfer catalyst (PTC),20b
2 h (17% plus isomers from migration of the double bond);
rongalite-NaOH-water-benzene PTC,19d 3 h (15-17%
plus products of double-bond migration); sodium hydride-
DMF,27 12 h (20%, complicated by reaction of Na2Te with
DMF27,28); sodium naphthalenide-THF,29 20 min (44%). We
have previously reported that the method of reduction of
tellurium could alter the outcome of some tellurium-triggered
reactions.19c Catalytic amounts (10 mol %) of tellurium with
stoichiometric LiEt3BH may be used, but the reaction is
slower (12 h) and the yield of 3a is lower (50%). The
presence of the Lewis acids, lithium ion, and triethylborane
(a byproduct in the reduction of tellurium) apparently is
helpful since the reaction seems to be somewhat inhibited
by the Lewis base, fluoride ion. The reaction of 2a with
lithium telluride in the presence of tetrabutylammonium
fluoride was slower and gave a lower yield of 3a (60% for
15 h vs 90% for 25 min, Table 1, entry 1). This result also
may be caused by some depletion of the telluride ion by
reaction with the quaternary salt.
The enolate from 2a can be trapped by reaction with
benzaldehyde to give syn- and anti-aldol products 11a14 and
11b,30 respectively, in 75-91% yield. Diastereoselectivity
of this aldol reaction varies depending on the temperature
and reaction time. The highly diastereoselective formation
of the syn-aldol 11a is kinetically controlled and observed
at low temperature, whereas the thermodynamically favored
anti-aldol 11b, resulting from a slow equilibration through
a retroaldol reaction, is formed at higher temperature, also
with a high degree of diastereoselectivity (Scheme 4). This
Scheme 4. Aldol Reaction of the Enolate Generated from 2a
with Telluride Ion
The reaction pathway for the nucleophilic ring opening
may be rationalized by initial substitution of the tosylate
(24) (a) Bergson, G. Acta Chem. Scand. 1957, 11, 571-572. (b) Engman,
L.; Cava, M. P. J. Org. Chem. 1982, 47, 3946-3949. (c) Clive, D. L. Y.;
Beaulieu, P. L. J. Org. Chem. 1982, 47, 1124-1126. (d) Osuka, A.; Suzuki,
H. Chem. Lett. 1983, 119-120. (e) Engman, L. Organometallics 1986, 5,
427-437. (f) Suzuki, H.; Inouye, M. Chem. Lett. 1986, 403-406. (g) Huang,
Z.; Xia, L.; Huang, X. Synth. Commun. 1988, 18, 1167-1170. (h) Matsuki,
T.; Hu, N. X.; Aso, Y.; Otsubo, T.; Ogura, F. Bull. Chem. Soc. Jpn. 1989,
62, 2105-2107. (i) Padmanabhan, S.; Ogawa, T.; Suzuki, H. Bull. Chem.
Soc. Jpn. 1989, 62, 2114-2116. (j) Li, C. J.; Harpp, D. N. Tetrahedron
Lett. 1990, 31, 6291-6294. (k) Huang, Z.-Z.; Zhou, X.-J. Synthesis 1990,
633-634. (l) Zhou, Z.-L.; Shi, L.-L.; Huang, Y.-Z. Synth. Commun. 1991,
21, 1027-1037. (m) Vasil’ev, A. A.; Engman, L. J. Org. Chem. 1998, 63,
3911-3917.
behavior closely resembles the aldol reaction of tert-butyl
n-butyl ketone with benzaldehyde reported by Heathcock and
Lampe.31 The aldol products 11a,b also have been obtained
by treatment of trimethylsilylmethylcyclopropyl tert-butyl
ketone and benzaldehyde with titanium tetrachloride at -78
°C (70%, anti/syn ) 1:11), with BF3‚Et2O (34%, anti/syn )
1.7:1), and with SnCl4 (40%, anti/syn ) 1:2).14
(25) For the use of the term “cyclopropanalogue”, see: Duffy, E. P. Ph.D.
Thesis, Tufts University, Boston, MA, 1987; Diss. Abstr. Int. B 1988, 48,
3568.
(26) 5-Allyl-1,3-cyclopentadiene was not detected. In addition, 1- and
5-allylcyclopentadienes are higher in energy than the 2-allylcyclopentadiene
by 0.545 and 3.859 kcal mol-1, respectively, according to the ab initio
calculations. A 60:40 ratio corresponds to a difference in energy of 0.240
kcal mol-1 at 298 K. The calculated energy difference of 0.545 kcal mol-1
is expected to afford a 72:28 mixture of isomers. Thermal 1,5-sigmatropic
rearrangements in the cyclopentadiene system can interconvert isomers. Our
reaction was carried out at room temperature. See Supporting Information.
(27) Suzuki, H.; Manabe, H.; Inouye, M. Chem. Lett. 1985, 1671-1674.
(28) Zingaro, R. A.; Herrera, C.; Meyers, E. A. J. Organomet. Chem.
1986, 306, C36-C40.
No reaction is observed under the conditions shown in
Scheme 2 if the acylcyclopropanemethanol 1b is used instead
(30) Anti-configuration of 11b was established on the basis of literature
analogies and by comparison with the known 11a:14 (a) Heathcock, C. H.;
Pirrung, M. C.; Sohn, J. E. J. Org. Chem. 1979, 44, 4294-4299. (b)
Ohtsuka, Y.; Koyasu, K.; Ikeno, T.; Yamada, T. Org. Lett. 2001, 3, 2543-
2546.
(29) Higa, K. T.; Harris, D. C. Organometallics 1989, 8, 1674-1678.
(31) Heathcock, C. H.; Lampe, J. J. Org. Chem. 1983, 48, 4330-4337.
Org. Lett., Vol. 6, No. 13, 2004
2227

of the tosylate 2b. This observation eliminates the possibility
that ring-opening occurs by one-electron transfer from
telluride ion to the carbonyl group to form a ketyl, but
it does not rule out intramolecular electron transfer
(Scheme 5). No significant difference in reactivity between
In conclusion, a novel nucleophilic intramolecular cyclo-
propane ring opening triggered by telluride ion has been
observed. The key reagent, elemental tellurium, is recovered
and can be reused. In addition, this reaction illustrates a
method of enolate generation without the use of strong bases
or strong Lewis acids. Further studies on the scope and
limitations of this method are currently underway.
Acknowledgment. Acknowledgment is made to the
donors of the Petroleum Research Fund, administered by the
American Chemical Society, and to Syracuse University for
support of this research. We thank Professor Tess Freedman
for the ab initio calculations. E.A. was supported for the
summer of 2002 by the NSF-Research Experience for
Undergraduates program.
Scheme 5. Possible One-Electron Transfer Mechanism
Supporting Information Available: Detailed experi-
mental procedures and characterization data for all com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
cis- and trans-cyclopropane isomers in a mixture of both
(mainly cis-isomer) was observed under the reaction condi-
tions used.
OL0492804
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Org. Lett., Vol. 6, No. 13, 2004