Palladium-mediated ring opening of hydroxycyclopropanes

Article abstract of DOI:10.1021/ol991250r

(matrix presented) The palladium-mediated ring opening of substituted cyclopropanols has been found to take place predominantly at the less substituted C-C bond. Thus, sequential application of the titanium-mediated cyclopropanation of esters and the palladium-mediated ring opening of the resulting cyclopropanols provides a convenient method for functionalizing monosubstituted olefins.

Full text of DOI:10.1021/ol991250r

ORGANIC
LETTERS
2
000
Vol. 2, No. 2
47-149
Palladium-Mediated Ring Opening of
Hydroxycyclopropanes
1
Soon-Bong Park and Jin Kun Cha*
Department of Chemistry, UniVersity of Alabama, Tuscaloosa, Alabama 35487
cha@jkc.ch.ua.edu
Received November 15, 1999
ABSTRACT
The palladium-mediated ring opening of substituted cyclopropanols has been found to take place predominantly at the less substituted C−C
bond. Thus, sequential application of the titanium-mediated cyclopropanation of esters and the palladium-mediated ring opening of the resulting
cyclopropanols provides a convenient method for functionalizing monosubstituted olefins.
The unique reactivity of cyclopropanes due to the high level
of strain offers considerable utility in organic synthesis. Many
imaginative applications of cyclopropanes as useful building
blocks have been predicated on regio- and stereocontrolled
The starting cyclopropanols were readily prepared by the
titanium-mediated cyclopropanation of carboxylic esters.4
The presence of the free alcohol on the cyclopropane ring
was anticipated to facilitate ring opening due to the inter-
,5
1
6
ring-opening reactions of substituted cyclopropanes. Typi-
mediacy of the metal alkoxide. Indeed, treatment of 1a and
cally, electrophilic opening has been achieved by transition
2
1b with Pd(OAc) in the presence of pyridine under an
+
+
metals (Pd, Pt, Rh, and Ir), halogens (Cl and Br ), and soft
atmosphere of oxygen gave the ring-opened products 2a and
2b in 55% and 88% yields, respectively (Table 1, entries 1
and 2).
2
+
3+ 2
Lewis acids (Hg and Tl ). The electron donor (particu-
larly, alkoxy, siloxy, and arylthio) substituted cyclopropanes
have found increasing use, primarily due to facile and
(3) (a) Kuwajima, I.; Nakamura, E. Top. Curr. Chem. 1990, 155, 1. (b)
3
regiocontrolled ring opening. Surprisingly, ring opening of
Ikura, K.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1992, 114,
1520. (c) Ryu, I.; Ikura, K.; Tamura, Y.; Maenaka, J.; Ogawa, A.; Sonoda,
N. Synlett 1994, 941. (d) Sugimura, T.; Futagawa, T.; Mori, A.; Ryu, I.;
Sonoda, N.; Tai, A. J. Org. Chem. 1996, 61, 6100. (e) Hoberg, J. O.;
Jennings, P. W. Organometallics 1996, 15, 3902. (f) Beyer, J.; Madsen, R.
J. Am. Chem. Soc. 1998, 120, 12137. (g) Ito, Y.; Fujii, S.; Nakatsuka, M.;
Kawamoto, F.; Saegusa, T. In Organic Synthesis; Norland, W. E., Ed.;
Wiley: New York, 1988; Collect. Vol. 6, p 327. (h) Booker-Milburn, K.
I.; Thompson, D. F. J. Chem. Soc., Perkin Trans. 1 1995, 2315. (i) Hoberg,
J. O. J. Org. Chem. 1997, 62, 6615. (j) Reference 1e. (k) Cohen, T.;
Brockunier, L. Tetrahedron 1989, 45, 2917 and references therein.
(4) (a) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.; Prityts-
kaya, 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.; Sorokin, V. L.; Kel’in, A. V.
Zh. Org. Khim. 1993, 29, 66.
(5) (a) Lee, J.; Kang, C. H.; Kim, H.; Cha, J. K. J. Am. Chem. Soc.
1996, 118, 291. (b) Lee, J.; Kim, H.; Cha, J. K. J. Am. Chem. Soc. 1996,
118, 4198. (c) Lee, J.; Ha, J. D.; Cha, J. K. J. Am. Chem. Soc. 1997, 119,
8127. (d) Ha, J. D.; Lee, J.; Blackstock, S. C.; Cha, J. K. J. Org. Chem.
1998, 63, 8510.
(6) Cf.: Nishimura, T.; Ohe, K.; Uemura, S. J. Am. Chem. Soc. 1999,
121, 2645.
unprotected hydroxycyclopropanes has been little explored.
Herein we report the palladium-mediated regioselective ring
opening of substituted cyclopropanols.
(1) For general reviews, see: (a) Gibson, D. H.; DePuy, C. H. Chem.
ReV. 1974, 74, 605. (b) Crabtree, R. H. Chem. ReV. 1985, 85, 245. (c)
Battiste, M. A.; Coxon, J. M. In The Chemistry of the Cyclopropyl Group;
Rappoport, Z., Ed.; Wiley: Chichester, U.K., 1987; Chapter 6. (d) Wong,
H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko, J.; Hudlicky, T.
Chem. ReV. 1989, 89, 165. (e) Trost, B. M. Top. Curr. Chem. 1986, 133,
3
.
(2) For recent representative examples, see: (a) Gassman, P. G.; Bonser,
S. M. Tetrahedron Lett. 1983, 24, 3431. (b) Campbell, W. H.; Jennings, P.
W. Organometallics 1983, 2, 1460. (c) Blomberg, M. R. A.; Siegbahn, P.
E. M.; B a¨ ckvall, J. E. J. Am. Chem. Soc. 1987, 109, 4450. (d) Jennings, P.
W.; Johnson, L. L. Chem. ReV. 1994, 94, 2241. (e) Kocovsky, P.; Srogl, J.;
Pour, M.; Gogoll, A. J. Am. Chem. Soc. 1994, 116, 186 and references
therein. (f) Hayashi, M.; Ohmatsu, T.; Meng, Y.-P.; Saigo, K. Angew. Chem.,
Int. Ed. 1998, 37, 837. (g) Wender, P. A.; Husfeld, C. O.; Langkopf, E.;
Love, J. A. J. Am. Chem. Soc. 1998, 120, 1940.
1
0.1021/ol991250r CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/30/1999

Table 1. Pd(II)-Mediated Ring Opening of Cyclopropanols
Scheme 1
1
1
3
). Under identical reaction conditions, the cyclopropanol
c afforded a 3.9:1 mixture of the two regioisomers 2c and
c in 87% yield (Table 1, entry 3). From the examination of
7
different conditions (such as use of DMSO ) and catalysts
(
entries 4-6), exclusive formation of 2c was achieved by
employing Pd (dba) and p-benzoquinone as a reoxidant
entry 6). Similar results were also obtained for cyclopro-
2
3
(
panols 1d (entries 7 and 8) and 1e (entries 9 and 10),
although ring opening of 1e was found to proceed with only
modest regioselectivity. At lower temperatures (e.g., 50 °C),
Scheme 2
We next examined the regioselectivity of Pd(II)-mediated
ring-opening reactions of substituted cyclopropanols (Scheme
(
7) For a unique role of DMSO, see: (a) Kagan, H. B.; Ronan, B. ReV.
Heteroat. Chem. 1992, 1, 92. (b) Larock, R. C.; Hightower, T. R. J. Org.
Chem. 1993, 58, 5298. (c) Semmelhack, M. F.; Kim, C. R.; Dobler, W.;
Meier, M. Tetrahedron Lett. 1989, 30, 4925.
(
8) For example, treatment of 2e with anhydrous FeCl3 at -20 °C (20
min) resulted in a Nazarov reaction to afford the fused cyclopentenone
product in 61% yield.
148
Org. Lett., Vol. 2, No. 2, 2000

ring opening took place more slowly and with insubstantial
enhancement in regioselectivity. Mechanistically, the Pd(II)-
alkoxide intermediate A undergoes ring opening of the less
substituted C-C bond (bond a) to produce an alkylpalladium
species B in preference to C (from scission of bond b).
Subsequent â-hydride elimination then affords the products
Table 2
2c-e and 3c-e. Finally, the Pd(II)-hydride or Pd(0) species
formed is converted to active Pd(II) by a reoxidant. The
pivotal role of the Pd(II)-alkoxide intermediate A was
demonstrated in a control experiment employing the tert-
butyldimethylsilyl ether (structure not shown) of 1c, which
was recovered unreacted.
Additional examples, mainly containing R- or â-substit-
uents adjacent to the cyclopropanol functionality, are shown
in Table 2. While the palladium-mediated ring-opening
reaction of cyclopropanols appears to be general, R-alkoxy-
substituted compounds (Table 2, entries 3-7) proved to be
sensitive to the catalyst and the reaction conditions.
On cursory examination, ring opening of bicyclic or
tricyclic cyclopropanols 1k-m revealed a preference for
cleavage of the more substituted C-C bond (bond b in
Scheme 1). The product distributions given in Scheme 2 are
kinetic in origin, since no changes were observed upon
resubjecting 2k-m or 3k-m to the identical reaction
conditions. Higher levels of ring strain associated with these
substrates can account for rapid ring opening and the opposite
regioselectivity.
It should be noted that the present method nicely comple-
ments Pt(II)-catalyzed isomerization of siloxycyclopropanes
to allyl silyl ethers by means of a 1,2-hydrogen shift.3b
Sequential application of the titanium-mediated cyclopro-
panation of esters and the palladium-mediated ring opening
of the resulting cyclopropanols should be of utility in organic
8
synthesis.
Acknowledgment. We thank the National Science
Foundation (Grant No. CHE98-13975) for financial
support.
OL991250R
Org. Lett., Vol. 2, No. 2, 2000
149