Acid- and Pd(0)-catalyzed ring opening of 1-(1-cycloalkenyl)cyclopropyl sulfonates

Article abstract of DOI:10.1021/ol701653x

(Chemical Equation Presented) We report herein facile acid-catalyzed isomerization of 1-(1′-cycloalkenyl)cyclopropyl sulfonates under mild conditions. The remarkable ease of ring opening is attributed to the presence of a 1′-alkyl substituent. Also includ

Full text of DOI:10.1021/ol701653x

ORGANIC
LETTERS
2007
Vol. 9, No. 22
4439-4442
Acid- and Pd(0)-Catalyzed Ring Opening
of 1-(1-Cycloalkenyl)cyclopropyl
Sulfonates
Long Guo Quan,† Hyung Goo Lee,‡ and Jin Kun Cha*,‡
Department of Chemistry, Yanbian UniVersity, Yanji, 133002, Jilin, China, and
Department of Chemistry, Wayne State UniVersity, 5101 Cass AVenue,
Detroit, Michigan 48202
jcha@chem.wayne.edu
Received July 25, 2007
ABSTRACT
We report herein facile acid-catalyzed isomerization of 1-(1
′-cycloalkenyl)cyclopropyl sulfonates under mild conditions. The remarkable ease
of ring opening is attributed to the presence of a 1 -alkyl substituent. Also included is a palladium-catalyzed ring opening reaction of 1-(1′-
′
cycloalkenyl)cyclopropyl tosylates for convenient preparation of substituted 1,3-dienylamines, which complements previously reported nucleophilic
substitution reactions of (1-vinyl)cyclopropyl tosylates.
Solvolysis of cyclopropyl sulfonates (or halides) was exten-
sively investigated and believed to involve a concerted
ionization-ring opening process.1 The cyclopropyl-allyl
rearrangement is thus viewed as a concerted 2π-electrocyclic
ring opening. Recent examples include synthetically useful
preparations of 2-substituted allylic bromides by the action
of magnesium bromide.2,3 A ring-closed cyclopropyl cation
can be trapped by a nucleophile in the presence of an
R-substituent (e.g., cyclopropyl or phenyl) that is capable
of stabilizing the developing positive charge. Surprisingly,
the effects of a C1-vinyl substituent on C2-C3 ring opening
or the intermediacy of the respective cyclopropyl cation have
not been fully elucidated.1 Additionally, it does not appear
that effects exerted by a 1′-alkyl group of the C1-vinyl
substituent were examined. We describe herein facile acid-
catalyzed isomerization of 1-(1′-cycloalkenyl)cyclopropyl
sulfonates under mild conditions. Also included are pal-
ladium-catalyzed ring opening reactions for convenient
preparation of highly substituted 1,3-dienes.
† Yanbian University.
‡ Wayne State University.
A 1-(1′-cycloalkenyl)cyclopropyl sulfonate was first cho-
sen as the substrate, in part, because the requisite cyclopro-
panol 2 was readily available by the Kulinkovich cyclopro-
panation of 1 (Scheme 1).4-7 We also reasoned that, when
(1) (a) Roberts, J. D.; Chambers, V. C. J. Am. Chem. Soc. 1951, 73,
5034. (b) Woodward, R. B.; Hoffmann, R. J. Am. Chem. Soc. 1965, 87,
395. (c) DePuy, C. H.; Schnack, L. G.; Hausser, J. W.; Wiedemann, W. J.
Am. Chem. Soc. 1965, 87, 4006. (d) Howell, B. A.; Jewett, J. G. J. Am.
Chem. Soc. 1971, 93, 798. (e) von R. Schleyer, P.; Sliwinski, W. F.; Van
Dine, G. W.; Schoellkopf, U.; Paust, J.; Fellenberger, K. J. Am. Chem.
Soc. 1972, 94, 125. For reviews, see: (f) Gibson, D. H.; DePuy, C. H.
Chem. ReV. 1974, 74, 605. (g) Aksenov, V. S.; Terent’eva, G. A.; Savinykh,
Y. V. Russ. Chem. ReV. (Engl. Transl.) 1980, 49, 549. (h) Salau¨n, J.
Rearragements involving the cyclopropyl group. In The Chemistry of the
Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987; p 809.
(i) Boche, G.; Walborsky, H. M. Cyclopropane DeriVed ReactiVe Intermedi-
ates; Wiley: New York, 1990; pp 117-173. (j) Jendralla, H. In Houben-
Weyl Methods of Organic Chemistry; Thieme: Stuttgart, 1997; Vol. E17c,
Chapter 2.4.1.3, pp 2313-2346.
(2) (a) Kozyrkov, Y. Y.; Kulinkovich, O. G. Synlett 2002, 443. (b)
Kulinkovich, O. G.; Kozyrkov, Y. Y.; Bekish, A. V.; Matiushenkov, E.
A.; Lysenko, I. L. Synthesis 2005, 1713. (c) Kozyrkov, Y. Y.; Kulinkovich,
O. G. Synlett 2004, 344.
(3) See also: (a) Kirihara, M.; Kambayashi, T.; Momose, T. J. Chem.
Soc., Chem. Commun. 1996, 1103. (b) Kirihara, M.; Kakuda, H.; Tsunooka,
M.; Shimajiri, A.; Takuwa, T.; Hatano, A. Tetrahedron Lett. 2003, 44, 8513.
(4) (a) Oh, H.-S.; Lee, H. I.; Cha, J. K. Org. Lett. 2002, 4, 3707. (b) Oh,
H.-S.; Cha, J. K. Tetrahedron: Asymmetry 2003, 14, 2911.
10.1021/ol701653x CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/29/2007

exposure to SiO2, 3 underwent facile ring opening at room
temperature (within 1 day) to afford the ring-opened, allylic
tosylate 4 cleanly (Scheme 2). No thermal rearrangement of
3 was observed (e.g., in a THF solution at reflux) in the
absence of SiO2. Several additional tosylates, 5, 7, 9, 11,
and 13, were next prepared to compare their reactivity toward
the cyclopropyl-allyl rearrangement.8 Both alkenyl and
phenyl R-substituents promote solvolysis. More importantly,
rate acceleration by an alkyl substituent at the 1′-position is
conspicuous (3 and 7 vs 5). The presence of an alkyl group
on the cyclopropane ring also quickens ring opening:1 partial
rearrangement of 11 was observed during aqueous workup.
As expected, no solvolysis of 13 was observed under
identical conditions.
These readily available tosylates (e.g., 4, 6, 8, and 10) are
well suited for subsequent elaboration such as direct dis-
placement and π-allylpalladium chemistry.9 Remarkably
facile ring opening of 3 (bearing a C1′-substituent) under
mild acidic conditions prompted us to speculate that the
π-allylpalladium complex derived from 3 could also undergo
C2-C3 ring opening (e.g., I f IIb, Scheme 3). Such a
Scheme 1
R1 * H, minimization of allylic strain would lead to
predisposition toward ring opening, as shown in conformer
A. Despite extensive studies on solvolysis of cyclopropanol
derivatives, known examples dealt with vinyl substituents
where R1 ) H.
Cyclopropanol 2 was converted to tosylate 3 in excellent
yield by standard methods (p-TsCl in pyridine). Upon
Scheme 2
Scheme 3
reaction pathway contrasts with leading contributions by
Salau¨n and de Meijere on Pd(0)-catalyzed substitution
(5) (a) Lee, J.; Kim, H.; Cha, J. K. J. Am. Chem. Soc. 1995, 117, 9919.
(b) Lee, J.; Kim, H.; Cha, J. K. J. Am. Chem. Soc. 1996, 118, 4198.
(6) For reviews on the Kulinkovich reaction, see: (a) Kulinkovich, O.
G.; de Meijere, A. Chem. ReV. 2000, 100, 2789. (b) Sato, F.; Urabe, H.;
Okamoto, S. Chem. ReV. 2000, 100, 2835. (c) Kulinkovich, O. G. Eur. J.
Org. Chem. 2004, 4517.
(7) In contrast to (1-cycloalkene)carboxylates, acyclic R,â-unsaturated
esters are poor substrates for the titanium-mediated cyclopropanation
reaction: (a) Racouchot, S.; Ollivier, J.; Salau¨n, J. Synlett 2000, 1729. (b)
Racouchot, S.; Sylvestre, I.; Ollivier, J.; Kozyrkov, Y. Y.; Pukin, A.;
Kulinkovich, O. G.; Salau¨n, J. Eur. J. Org. Chem. 2002, 2160.
(8) (a) The respective cyclopropanols were prepared (a) by the Kulink-
ovich cyclopropanation (in the case of 7, 9, 11, and 13) or (b) via the
cyclopropanone hemiacetal (in the case of 5). (b) Other acids (e.g., PPTS,
p-TsOH) or Lewis acids are also effective for ring opening. (c) Tosylates
were used in this study because of their crystalline properties, whereas other
sulfonates also gave comparable results.
4440
Org. Lett., Vol. 9, No. 22, 2007

reactions, which proceed with retention of the three-
membered ring with excellent regioselectivity (I f III and
I f IV) depending on the nature of the nucleophiles.10,11 In
subsequent mechanistic studies, a hindered amine was chosen
as the nucleophile to preclude side reactions due to small
amounts of acidic impurities.12 Under original conditions
reported by Salau¨n and de Meijere, i.e., 2-5 mol % of
Pd(dba)2/dppe (1:2) as catalyst in THF at reflux, the starting
tosylate 3 remained unchanged with formation of only trace
amounts of 14 in the presence of diisopropylamine (2 equiv).
By employing 5 mol % of Pd2(dba)3 and 20 mol % of Ph3P
in refluxing THF, 14 was obtained as the sole product in
88% yield (Scheme 4). Use of other amines also provided
Scheme 5
Scheme 4
potential complication due to the otherwise facile ring
expansion pathway (i.e., the cyclopropylcarbinyl f cyclobu-
tyl rearrangement) that could be induced by Pd(II) or acidic
impurities.4,14-16
Other nucleophiles, which the Salau¨n and de Meijere
groups had used,10 were next examined for comparison
studies: the nature of nucleophiles and the ligands (e.g.,
monodentate vs bidentate) also affected the reaction course.
Pd(0)-catalyzed reactions with NaN3 or potassium acetate
15-17 in good yields. In the case of aniline, use of 3 equiv
was beneficial. When 2 equiv was employed, 17 was isolated
in 66% yield, along with the bisalkylation product 18 (11%).
Similarly, 20 was prepared in comparable yield from 19.
When Ph3P was employed as the nucleophile in place of an
amine, the phosphonium salt 21 was obtained in quantitative
yield (Scheme 5).13 Use of the sulfonates precluded the
(9) For example, treatment of 4 with sodium malonate or KOAc under
typical π-allylpalladium reaction conditions yielded the corresponding
displacement products in excellent yields.
(14) (a) Trost, B. M. Top. Curr. Chem. 1986, 133, 3. (b) Trost, B. M.;
Brandi, A. J. Am. Chem. Soc. 1984, 106, 5041. (c) Trost, B. M.; Lee, D. C.
J. Am. Chem. Soc. 1988, 110, 6556. (d) Trost, B. M.; Chen, D. W. C. J.
Am. Chem. Soc. 1996, 118, 12541.
(15) For a review, see: (a) Salau¨n, J. Top. Curr. Chem. 1988, 144, 1.
Cf. (b) Boontanonda, P.; Grigg, R. J. Chem. Soc., Chem. Commun. 1977,
583. (c) Clark, G. R.; Thiensathit, S. Tetrahedron Lett. 1985, 26, 2503. (d)
Nemoto, H.; Shiraki, M.; Fukumoto, K. Synlett 1994, 599. (e) Mitchell,
D.; Liebeskind, L. S. J. Am. Chem. Soc. 1990, 112, 291. (f) Larock, R. C.;
Reddy, C. K. Org. Lett. 2000, 2, 3325. (g) Yoshida, M.; Sugimoto, K.;
Ihara, M. Org. Lett. 2004, 6, 1979.
(10) (a) Stolle, A.; Salau¨n, J.; de Meijere, A. Tetrahedron Lett. 1990,
31, 4593. (b) Stolle, A.; Ollivier, J.; Piras, P. P.; Salau¨n, J.; de Meijere, A.
J. Am. Chem. Soc. 1992, 114, 4051. (c) Aufranc, P.; Ollivier, J.; Stolle, A.;
Bremer, C.; Es-Sayed, M.; de Meijere, A.; Salau¨n, J. Tetrahedron Lett.
1993, 34, 4193. (d) Atlan, V.; Racouchot, S.; Rubin, M.; Bremer, C.;
Ollivier, J.; de Meijere, A.; Salau¨n, J. Tetrahedron: Asymmetry 1998, 9,
1131. (e) Lecornue´, F.; Charnay-Pouget, F.; Ollivier, J. Synlett 2006, 1407.
(11) For a review, see: Salau¨n, J. Chem. ReV. 2005, 105, 285.
(12) In view of lability of 3 toward SiO2, no silica gel column
chromatography was undertaken for purification. Instead, an aqueous workup
procedure, followed by trituration or recrystallization, was used to secure
3: experimental details are given in the Supporting Information.
(13) Wittig olefination of 21 with octanal in the presence of n-BuLi took
place smoothly to give the corresponding triene (structure not shown) as a
6:1 mixture of E- and Z-isomers in 68% (unoptimized) yield.
(16) To exclude the possible intermediacy of the allyl tosylate 4 by an
initial rearrangement, a control experiment was performed without a
palladium catalyst, in which the starting tosylate 3 was recovered unreacted.
Additionally, aromatic and alkyl cyclopropyl tosylates 9 and 13 were stable
under these conditions. The selective formation of 23 is in accord with the
intermediacy of a π-allylpalladium complex, and an alternate cyclopropyl-
allyl rearrangement induced by a Pd(II) species might be ruled out.
Org. Lett., Vol. 9, No. 22, 2007
4441

in the presence of 18-crown-6 displayed the regioselectivity
(i.e., 22 and 23) identical to literature results.10,16,17 On the
other hand, the cognate reactions with malonates hinged upon
reaction conditions: use of diethyl malonate, K2CO3, and
18-crown-6 (conditions I) gave 24 in 57% yield. Adaptation
of Salau¨n and de Meijere’s conditions (conditions II) afforded
a 1:3.4 mixture of 24 and 25 in 75% yield. These results
contrast with exclusive formation of 2-cyclopropylidene
esters from acyclic 1-(1′-vinyl)cyclopropyl sulfonates.10,11
Although full elucidation of key factors that control the
reaction pathways must await further studies, the π-allyl-
palladium complexes derived from 1-(1′-cycloalkenyl)-
cyclopropyl sulfonates seem to be predisposed toward ring
opening. This propensity toward ring opening might be
attributed to minimization of allylic strain (see A in Scheme
1).18
substituted 1,3-dienes. The ease of acid-catalyzed ring
opening is particularly noteworthy and could be attributed
to quite large accelerating effects of 1′-substitution on ring
opening. The palladium-mediated ring opening of 1-(1′-
cycloalkenyl)cyclopropyl tosylates presents an interesting
contrast to nucleophilic substitutions of (1-vinyl)cyclopropyl
tosylates with retention of the three-membered ring. Since
the starting (1′-cycloalkenyl)cyclopropanols are readily avail-
able by the Kulinkovich reaction of cycloalkene carboxylates,
the present method provides convenient access to function-
alized 1,3-dienes starting from esters.
Acknowledgment. We thank the National Institutes of
Health (GM35956) and the National Science Foundation
(CHE-0615604) for generous financial support.
Supporting Information Available: Additional examples
of palladium-catalyzed reactions of 1-(1′-alkenyl)cyclopropyl
tosylates, along with experimental details and spectroscopic
data for key intermediates. This material is available free of
charge via the Internet at http://pubs.acs.org.
In summary, the acid- and palladium-catalyzed ring
opening reactions of 1-(1′-cycloalkenyl)cyclopropyl sul-
fonates were investigated for the facile preparation of highly
(17) Allylic azides are known to undergo facile equilibration by [3,3]-
sigmatropy, which complicates mechanistic analysis: (a) Vander Werf, C.
A.; Heisler, R. Y.; McEwen, W. E. J. Am. Chem. Soc. 1954, 76, 1231. (b)
Gagneux, A.; Winstein, S.; Young, W. G. J. Am. Chem. Soc. 1960, 82,
5956. (c) Feldman, A. K.; Colasson, B.; Sharpless, K. B.; Fokin, V. V. J.
Am. Chem. Soc. 2005, 127, 13444.
OL701653X
(18) Additional comparison studies are available in the Supporting
Information.
4442
Org. Lett., Vol. 9, No. 22, 2007