A new preparation of cyclopropanone hemiketals by reductive coupling of terminal olefins with ethylene carbonate

Full text of DOI:10.1021/jo960856f

4878
J . Org. Chem. 1996, 61, 4878-4879
A New P r ep a r a tion of Cyclop r op a n on e
Hem ik eta ls by Red u ctive Cou p lin g of
Ter m in a l Olefin s w ith Eth ylen e Ca r bon a te
J inhwa Lee,1a Young Gyu Kim,1b
J ae Gwang Bae,1b and J in Kun Cha*,†,1a
Department of Chemistry, University of Alabama,
Tuscaloosa, Alabama 35487, and Department of Chemical
Technology, Seoul National University, Seoul, Korea
Received May 9, 1996
Since cyclopropanone was first implicated as the key
reaction intermediate in the Favorskii rearrangement,
this small-ring compound has attracted considerable
attention from theoretical and synthetic chemists.2 A few
notable examples notwithstanding,3 cyclopropanones are
usually not isolated in a pure state because of their
extreme instability. They are known to readily suffer
polymerization, nucleophilic attack, or ring-opening. In
the presence of an alcohol, for example, they undergo
facile formation of the corresponding hemiketals, which
can be viewed as convenient synthetic equivalents of the
parent cyclopropanone functionality.4,5 Only a handful
of methods exist for the preparation of these synthetically
useful cyclopropanone hemiketals.6 Herein we report a
new, general synthetic method for cyclopropanone hemi-
ketals by utilizing Ti(II)-mediated coupling of monosub-
stituted olefins with ethylene carbonate.
Our approach evolved from the previously reported
facile preparation of cyclopropanols 3 by reductive cou-
pling of terminal olefins 1 with alkyl carboxylates 2 (eq
1).7 This new hydroxycyclopropanation, in turn, stemmed
from the original Kulinkovich procedure (eq 2).8,9 We
reasoned that an analogous application of our new
hydroxycyclopropanation to the use of a carbonate in lieu
of an alkyl carboxylate might provide an expeditious
synthesis of cyclopropanone hemiketals. When cyclo-
hexylmagnesium chloride (5 equiv) was slowly (during
30-60 min) added at -5 °C to a THF solution of olefin
1a (1.0-1.5 equiv), diethyl carbonate (1.0 equiv), and
ClTi(O-i-Pr)3 or Ti(O-i-Pr)4 (1.0 equiv), the desired cyclo-
propanone hemiketal 4 was indeed isolated, albeit in poor
(25-30%) yield [based on the consumed (27%) starting
material], along with unidentified byproducts (eq 3).10a
Interestingly, substitution of ethyl chloroformate for
diethyl carbonate also afforded the hemiketal 4 (37%
yield) and the cyclopropanol 5 (25% yield) (based on 36%
consumption of the olefin 1a ); the latter product must
be derived from ethyl cyclohexanecarboxylate, which was
generated in situ. Despite considerable experimentation,
both reactions proved to be recalcitrant toward optimiza-
tion. When cyclopentylmagnesium chloride was em-
ployed, both reactions resulted in even poorer yield.11
Subsequently, a reliable reaction protocol was found
by use of ethylene carbonate. Under otherwise identical
reaction conditions, the intermolecular reductive coupling
of the olefin 1a and ethylene carbonate took place
smoothly at 0 °C to give the cyclopropanone hemiketal
6a ,b in 47% isolated yield as a 2:1 diastereomeric mixture
(eq 4).10b Similarly, use of propylene 1,3-carbonate also
afforded the corresponding hemiketal 6c in 53% isolated
yield and as a single diastereomer.10b In contrast to
hydroxycyclopropanations of alkyl carboxylates,7a these
hemiketal-forming reactions were found to be sensitive
to the reaction temperature as outlined in eq 4, where 0
°C was found to be the optimum temperature. Additional
† Recipient of an NIH Research Career Development Award, 1990-
1995 (GM-00575).
(1) (a) Department of Chemistry, University of Alabama, Tuscaloosa,
AL 35487. (b) Department of Chemical Technology, Seoul National
University, Seoul, Korea.
(2) For general reviews, see: (a) Turro, N. J . Acc. Chem. Res. 1969,
2, 25. (b) Wasserman, H. H.; Clark, G. M.; Turley, P. C. Top. Curr.
Chem. 1974, 47, 73. (c) Wasserman, H. H.; Berdahl, D. R.; Lu, T.-J . In
The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley:
Chichester, 1987; Chapter 23.
(3) The bulky tert-butyl-disubstituted cyclopropanes are shown to
be stable at room temperature: (a) Pazos, J . F.; Greene, F. D. J . Am.
Chem. Soc. 1967, 89, 1030. (b) Crandall, J . K.; Machleder, W. H. J .
Am. Chem. Soc. 1968, 90, 7347. (c) Camp, R. L.; Greene, F. D. J . Am.
Chem. Soc. 1968, 90, 7349.
(4) Salau¨n, J . Chem. Rev. 1983, 83, 619.
(5) 1-Siloxy-1-alkoxycyclopropanes have been utilized as the homo-
enolate anion precursors: Kuwajima, I.; Nakamura, E. Top. Curr.
Chem. 1990, 155, 1.
(6) Among these methods are addition of diazoalkanes to ketenes
in the presence of an alcohol, acyloin-type cyclization of 3-chloropro-
panoate, and the Simmons-Smith cyclopropanation of ketene trimeth-
ylsilyl ketals.
(7) (a) Lee, J .; Kim, H.; Cha, J . K. J . Am. Chem. Soc. 1996, 118,
4198. See also: (b) Lee, J .; Kang, C. H.; Kim, H.; Cha, J . K. J . Am.
Chem. Soc. 1996, 118, 291. (c) Lee, J .; Kim, H.; Cha, J . K. J . Am. Chem.
Soc. 1995, 117, 9919.
(8) (a) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.;
Pritytskaya, T. S. Zh. Org. Khim. 1989, 25, 2244. (b) Kulinkovich, O.
G.; Sviridov, S. V.; Vasilevskii, D. A.; Savchenko, A. I.; Pritytskaya, T.
S. Zh. Org. Khim. 1991, 27, 294. (c) Kulinkovich, O. G.; Sviridov, S.
V.; Vasilevskii, D. A. Synthesis 1991, 234. (d) Kulinkovich, O. G.;
Vasilevskii, D. A.; Savchenko, A. I.; Sviridov, S. V. Zh. Org. Khim. 1991,
27, 1428. (e) For use of tributyl vanadate, see: Kulinkovich, O. G.;
Sorokin, V. L.; Kel’in, A. V. Zh. Org. Khim. 1993, 29, 66.
(9) (a) de Meijere, A.; Kozhushkov, S. I.; Spaeth, T.; Zefirov, N. S.
J . Org. Chem. 1993, 58, 502. (b) See also: Chaplinski, V.; de Meijere,
A. Angew. Chem., Int. Ed. Engl. 1996, 35, 413.
(10) (a) The product 4 was obtained as a single diastereomer, and
the indicated stereochemical assignment was made on the basis of
difference NOE measurements. (b) The stereochemistry of the products
6a -c was assigned on the basis of difference NOE measurements;
NOEs from the cyclopropane ring protons, including the -OH proton,
provided
a reliable guide to their stereochemical assignment. (c)
Hemiketals 7-10 were obtained as a 4:1-5:1 mixture of the â-H and
R-H diastereomers.
(11) More recently, we discovered that use of cyclopentylmagnesium
chloride (rather than cyclohexylmagnesium chloride) provides uni-
formly higher yields of cyclopropanols from alkyl carboxylates: Lee,
J .; Cha, J . K. Unpublished results.
S0022-3263(96)00856-0 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 15, 1996 4879
The intramolecular process employing ethyl 3-bute-
nylcarbonate (12) did not give rise to the highly strained
cyclic hemiketal 13, which would be expected to rapidly
undergo Favorskii-type ring opening to afford γ-lactone
14.15 Instead, treatment of 12 with cyclopentylmagne-
sium chloride (2.2 equiv) at 0 °C in the presence of ClTi-
(O-i-Pr)3 (1.0 equiv) produced ethyl 4-hydroxy-2-meth-
ylbutanoate (15) in 55% yield.15b A slightly higher (64%)
yield was obtained when the reaction was performed at
-40 °C.
examples are summarized in Table 1.12 This transforma-
tion appears to be general and would be compatible with
the presence of other functional groups in the olefin
partner. These hemiketals 6-10 bearing a â-hydroxy-
Ta ble 1. Cou p lin g of Olefin s 1a -e w ith Eth ylen e
Ca r bon a te10c
In summary, we have developed a new, general method
for the synthesis of cyclopropanone hemiketals by utiliz-
ing reductive coupling of terminal olefins with ethylene
carbonate. While reaction yields are moderate, a broad
range of functional groups can be conveniently introduced
into the otherwise inaccessible target compounds. Other
salient features include the ease of operation and the
ready availability of inexpensive reagents. Further syn-
thetic and mechanistic studies are currently in progress.
ethoxy substituent appear to be considerably less stable
than the counterparts containing an ethoxy moiety (i.e.,
4). For additional characterization, the hemiketal 6a ,b
was converted in 56% yield to the cyclopropylidene ester
11 by treatment with (carbethoxymethylene)triphen-
ylphosphorane in the presence of benzoic acid.13,14
Ack n ow led gm en t. We are grateful to the National
Institutes of Health (GM35956) for generous financial
support. J .L. also thanks The University of Alabama
for a graduate fellowship. We are indebted to Brian J .
Nobes (Clinical Pharmacology, Vanderbilt University)
for obtaining nominal and accurate mass spectra.
(12) A representative experimental procedure is given below: to a
solution of ethylene carbonate (0.24 g, 2.73 mmol) and 1-(triisopropyl-
siloxy)-3-butene (1a ) (0.21 g, 0.91 mmol) in 10 mL of THF was added
ClTi(O-i-Pr)3 (0.9 mL of 1.0 M solution in hexane, 1.0 equiv). Com-
mercially available cyclopentylmagnesium chloride (2.7 mL of 2.0 M
solution in ether) was added at 0 °C over a period of 30 min (syringe
pump). The reaction mixture was then stirred for an additional 1 h
and poured into water (15 mL). The organic layer was separated, and
the aqueous layer was extracted with ether (3 × 10 mL). The combined
extracts were washed with brine (10 mL) and dried over MgSO4.
Filtration and evaporation in vacuo gave the crude product. Purifica-
tion by column chromatography on silica gel afforded 0.14 g (47%) of
hemiketal 6a ,b as a 2:1 diastereomeric mixture (a colorless oil).
(13) Cf. (a) Osborne, N. F. J . Chem. Soc., Perkin Trans. 1 1982, 1435.
(b) Ru¨chardt, C.; Eichler, S.; Panse, P. Angew. Chem., Int. Ed. Engl.
1963, 2, 619.
Su p p or t in g In for m a t ion Ava ila b le: Characterization/
spectral data (14 pages).
J O960856F
(15) (a) Very recently, Sato and co-workers reported the identical
reaction of 12, in which the γ-lactone 14 was obtained in 92% yield
with use of i-PrMgCl at -40 °C: Okamoto, S.; Kasatkin, A.; Zubaidha,
P. K.; Sato, F. J . Am. Chem. Soc. 1996, 118, 2208. Under Sato’s reaction
conditions, we believe the actual product was also ester 15, which
underwent facile lactonization during workup with 3 N HCl. (b) Indeed,
in our hands, the experimental procedure of Sato gave 70% of 15 and
4% of 14, when the reaction was quenched with addition of water in
lieu of 3 N HCl. Moreover, treatment of 15 with 3 N HCl at room
temperature gave the lactone 14 in quantitative yield.
(14) A tandem application of our cyclopropanation protocol and
Wittig olefination thus provides a new, convenient synthetic method
for alkylidenecyclopropanes.