Selective syntheses of Δα,β and Δβ,γ butenolides from allylic cyclopropenecarboxylates via tandem ring expansion/[3,3]-sigmatropic rearrangements

Article abstract of DOI:10.1021/ol400264a

Allylic cyclopropenecarboxylates undergo ring expansion reactions to give 2-allyloxyfuran intermediates, which subsequently rearrange to Δ^β,γ butenolides via a Claisen rearrangement or to the corresponding Δ^α,β butenolides via further Cope rearrangement. Also described are methods for chirality transfer in the rearrangement of nonracemic allylic esters.

Full text of DOI:10.1021/ol400264a

ORGANIC
LETTERS
Selective Syntheses of Δr,β and Δβ,γ
Butenolides from Allylic
2013
Vol. 15, No. 7
1500–1503
Cyclopropenecarboxylates via Tandem
Ring Expansion/[3,3]-Sigmatropic
Rearrangements
Xiaocong Xie, Yi Li, and Joseph M. Fox*
Brown Laboratories, Department of Chemistry and Biochemistry,
University of Delaware, Newark, Delaware 19716, United States
jmfox@udel.edu
Received January 29, 2013
ABSTRACT
Allylic cyclopropenecarboxylates undergo ring expansion reactions to give 2-allyloxyfuran intermediates, which subsequently rearrange to Δβ,γ
butenolides via a Claisen rearrangement or to the corresponding ΔR,β butenolides via further Cope rearrangement. Also described are methods
for chirality transfer in the rearrangement of nonracemic allylic esters.
Compoundswith ΔR,β and Δβ,γ butenolidesubstructures
have received much interest for their utility in synthesis1
and their prevalence in biologically active molecules and
natural products.2 A number of methods for preparing
ΔR,β butenolides involve the reactivity of furan derivatives,
including asymmetric variants based on the Michael,3
MukaiyamaÀMichael,4 vinylogous Mannich,5 MoritaÀ
BaylisÀHillman,6 and aldol reactions7 that utilize siloxy-
furans to provide enantiomerically enriched ΔR,β buteno-
lides. There are also a number of enantiospecific syntheses
of ΔR,β butenolides in which epoxides8 or allenoates9 are
used as precursors.
Relative to methods for preparing ΔR,β butenolides,1d,10
the methods for accessing Δβ,γ isomers are few, especially
for butenolides that bear a quaternary R-stereocenter.
(1) (a) Rao, Y. S. Chem. Rev. 1964, 64, 353. (b) Rao, Y. S. Chem. Rev.
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r
10.1021/ol400264a
Published on Web 03/20/2013
2013 American Chemical Society

Cycloisomerization and iodolactonization reactions have
been used in the construction of Δβ,γ butenolides that bear
R-quaternary stereocenters.11 Vedejs12 and Smith13 have
catalyzed carboxyl migration reactions of 5-arylfuran de-
rived enol carbonates to give ΔR,β and Δβ,γ butenolides.12
Burger has demonstrated that allylic alkoxides can engage
2-fluoro-3-trifluoromethylfurans in tandem SNAr/Claisen
reactivity to produce Δβ,γ butenolides.14 Recently, Ma
described iodide catalyzed, regioselective alkylation of
2-methoxyfuran-3-carboxylic esters to give ΔR,β and Δβ,γ
butenolides.15
Very recently, Arseniyadis and Cossy have elegantly
reported enantioselective TsujiÀTrost type reactions16 of
allyl furan-2-yl carbonates.17 Quaternary centers were
established in 69À90% ee to give Δβ,γ butenolides via
Claisen rearrangement and the corresponding ΔR,β bute-
nolides via further Cope rearrangement.17
prepared by catalytic cyclopropenation of alkynes. The
conversion of cyclopropene carboxylic esters to 2- alkox-
yfurans is a well-known transformation that can be cata-
lyzed by a variety of metals,19 and elegant studies have
extended the scope of such reactions to the synthesis of
fused heterocycles.18 Of the catalysts that promote ring
expansionofcyclopropenes, Rh-basedcatalystsareamong
the most useful, and one-pot syntheses of furans from
alkynes and diazo compounds have been achieved.19À21
Furthermore, Rh(I) and Rh(II) catalysts lead to distinct
regioselectivities in the ring expansion. Liebeskind19a and
Padwa22 have proposed a mechanism that describes the
differing regioselectivities induced by Rh(I) and Rh(II)
catalysts.
We envisioned that readily prepared allylic cycloprope-
necarboxylates (A) could engage in ring expansion reac-
tions to give 2-allyloxyfuran intermediates (B) and that the
resulting allyloxyfurans would subsequently rearrange to
Δβ,γ butenolides (C) via Claisen rearrangement or to the
corresponding ΔR,β butenolides (D) via further Cope re-
arrangement (Scheme 1). Herein, we describe catalytic
methods for realizing these processes and for selective
formation of either Δβ,γ or ΔR,β butenolides (C vs D).
The procedure is not restricted to the reactivity of simple
allyl esters, but it also functions for prenyl esters, progargyl
esters, and esters derived from cyclic and acyclic secondary
allylic alcohols. For more substituted analogs of A, we
describe methods for controlling regioselectivity and chir-
ality transfer from nonracemic allylic esters. Our work
complements the very recent work of Arseniyadis and
Cossy, where asymmetric catalysis is used to transfer
unfunctionalized allyl groups.17a
Scheme 1. Tandem Ring Expansion/Claisen Rearrangements
Cyclopropene carboxylic esters are attractive precursors
for the preparation of butenolides,18 as they can be readily
(9) Liu, H.-J.; Leow, D.-S.; Huang, K.-W.; Tan, C.-H. J. Am. Chem.
Soc. 2009, 131, 7212.
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2000, 65, 4131. (b) Zhang, Q.; Cheng, M.; Hu, X.-Y.; Li, B.-G.; Ji, J.-X.
J. Am. Chem. Soc. 2010, 132, 7256. (c) Shi, Y.-L.; Roth, K. E.; Ramgren,
S. D.; Blum, S. A. J. Am. Chem. Soc. 2009, 131, 18022.
(11) (a) Trost, B. M.; McClory, A. Angew. Chem., Int. Ed. 2007, 46,
2074. (b) Komeyama, K.; Takahashi, K.; Takaki, K. Chem. Lett. 2008,
37, 602. (c) Dabrowski, J. A.; Gao, F.; Hoveyda, A. H. J. Am. Chem.
Soc. 2011, 133, 4778. (d) Shi, H.; Fang, L.; Tan, C.; Shi, L.; Zhang, W.;
Li, C.-C.; Luo, T.; Yang, Z. J. Am. Chem. Soc. 2011, 133, 14944.
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Vedejs, E. J. Am. Chem. Soc. 2006, 128, 925.
In general, allylic cycloprop-2-enecarboxylates could be
prepared in good yields by alkylation of the corresponding
acids with allylbromide/DBU or by Steglich esterification.
The rearrangement to Δβ,γ butenolides was first studied
with allylic esters of cycloprop-2-enecarboxylates with-
out vinylic substitution. A number of catalysts were
surveyed, and Rh2(OPiv)4 was found to be highly effec-
tive. Allyl 3-phenylcycloprop-2-enecarboxylate (1a)
gave butenolide 2a in 90% yield. Also rearrangements of
(13) Joannesse, C.; Morrill, L.; Campbell, C.; Slawin, A.; Smith, A.
Synthesis 2011, 2011, 1865.
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Lett. 2001, 1657. (b) Burger, K.; Hennig, L.; Fuchs, A.; Greif, D.;
Spengler, J.; Albericio, F. Monatsh. Chem. 2005, 136, 1763. (c) Burger,
K.; Fuchs, A.; Hennig, L.; Helmreich, B.; Greif, D. Monatsh. Chem.
2001, 132, 929.
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15044. (b) Burger, E. C.; Tunge, J. A. Org. Lett. 2004, 6, 4113. (c) Trost,
B. M.; Xu, J. J. Am. Chem. Soc. 2005, 127, 2846.
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Sato, H.; Hiroi, K. Tetrahedron Lett. 2006, 47, 5793.
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Tetrahedron 2010, 66, 1261. (b) Li, H.-Y.; Hsung, R. P. Org. Lett.
2009, 11, 4462. (c) Peng, L.-L.; Zhang, X.; Ma, M.; Wang, J.-B. Angew.
Chem., Int. Ed. 2007, 46, 1905. (d) Hamaguchi, M.; Tomida, N.; Iyama,
Y. J. Org. Chem. 2007, 72, 1326. (e) Wyatt, E. E.; Fergus, S.; Galloway,
W. R. J. D.; Bender, A.; Fox, D. J.; Plowright, A. T.; Jessiman, A. S.;
Welch, M.; Spring, D. R. Chem. Commun. 2006, 3296. (f) Ma, S.-M.; Lu,
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L.-H.; Lu, P. J. Org. Chem. 2005, 70, 1063. (g) Muller, P.; Allenbach,
(17) (a) Fournier, J.; Lozano, O.; Menozzi, C.; Arseniyadis, S.;
Cossy, J. Angew. Chem., Int. Ed. 2013, 52, 1257–1261. (b) Fournier, J.;
Arseniyadis, S.; Cossy, J. Angew. Chem., Int. Ed. 2012, 51, 7562.
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Org. Lett., Vol. 15, No. 7, 2013
1501

3-phenylcycloprop-2-enecarboxylates (1bÀe) derived
from secondary allylic alcohols were studied. Successful
rearrangements were realized with substrates with n-pentyl
(1b,c), phenyl (1d), or o-tolyl (1e) substituents at the allylic
position to give 2bÀe in 58À81% yields.
controlled by a chair transition state (F) with the allylic
substituent in an equatorial position. This model predicts
that the absolute configuration of the butenolides G is set
by the absolute configuration of the ester side chain of
cyclopropene E, which can be readily derived from
enantiomerically enriched allylic alcohols. Chirality
transfer was measured for the rearrangements of cyclo-
propenes 1b and 1c. For 1b, a high conversion of enan-
tiomeric excess (96% cee) was indeed observed, and the
absolute configuration was confirmed by conversion to
(S)-3-allyl-3-methylfuran-2(3H)-one.17 Chirality transfer
was also observed for the reaction of 1c to 2c (at 60 °C),
albeit with a reduced conversion of enantiomeric excess
(81% cee).22 The ready availability of nonracemic allylic
alcohols makes the method presented in Scheme 2 an
attractive method for the synthesis of enantiomerically
enriched butenolides.
As shown in Scheme 2, cyclohex-2-en-1-yl ester 1f
rearranges to compound 2f in 87% yield and with >95:5
diastereoselectivity. Propargyl ether 1g also undergoes
tandem ring expansion/Claisen rearrangement to give
R-allenyl-R-phenyl-Δβ,γ butenolide (2g) in 85% yield. Also
successful was the rearrangement of a cyclopropene that is
substituted at both the vinylic and allylic positions. Bute-
nolide 2h was obtained in 48% yield by a two-step proce-
dure, in which the intermediate ester was purified only by
filtration through a plug of silica gel. The relatively low yield
of 2h was a result of the difficulty of this particular Steglich
esterification, and not the Rh-catalyzed rearrangement.
Scheme 3. Model for Chirality Transfer
Scheme 2. Tandem Ring-Expansion/Claisen Rearrangements
Rh(I) andRh(II) catalystsleadto distinct regioselectivities
in the ring expansion of cyclopropenecarboxylates.17a,20
We hypothesized that allylic cycloprop-2-enecarboxy-
lates with C-2 substitution would undergo rearrangement
to allyloxyfurans and subsequently to Δβ,γ butenolides
with catalyst-dependent regioselectivity (Scheme 4). In-
deed, we found that treatment of 1i with Wilkinson’s
catalyst in refluxing benzene gave 4 in 92% yield via
putative intermediate I. Conversely, treatment of 1i with
Rh2(OPiv)4 leads to the complementary regioisomer 3 in
94% yield via putative H. Consistent with this mecha-
nism,19a,22 nonracemic 1i (82% ee) gives racemic 4 in a
reaction catalyzed by Wilkinson’s catalyst.
Scheme 4. Regioselective Expansion/Claisen Rearrangement
Because compounds 2 are 1,5-dienes, it was anticipated
that they could undergo a Cope rearrangement subsequent
to the Claisen rearrangement at elevated temperature and
that the sequence of ring expansion/Claisen/Cope rearran-
gement could take place in one flask. As displayed in
A model set forth in Scheme 3 predicts that the tandem ring
expansion/Claisen rearrangements would be stereospecifically
1502
Org. Lett., Vol. 15, No. 7, 2013

rationalized via successive chair transition states, as shown
at the bottom of Scheme 5. With enantiomerically enriched
1c, compound 5c was obtained with 83% ee. To see if the
Cope rearrangement is Rh-catalyzed, the rate of the
Scheme 5. Expansion/Claisen/Cope Rearrangements
1
transformation of 2d to 5d was measured by H NMR
(0.04 M in toluene-d6, 100 °C). Without the catalyst, the
rate was measured to be 6.0 Â 10À4 sÀ1. For an identical
experiment with 10 mol % Rh2(OPiv)4, the rate was
measured as 5.9 Â 10À4
s
À1. These data suggest that the
Cope rearrangement step is not catalyzed by Rh2(OPiv)4.
As was observed in the synthesis of Δβ,γ butenolides,
catalyst-dependent regioselectivity could be realized for
ΔR,β butenolide synthesis via the rearrangement of cyclo-
propene 1i, which is substituted at the vinylic position of
the cyclopropene. Thus, 1i rearranged to 6 in 94% yield
utilizing Wilkinson’s catalyst at 110 °C, whereas 7 was
formed in 46% yield when Rh2(OPiv)4 was employed as
the catalyst (Scheme 6).
In summary, we describe that allylic cyclopropenecar-
boxylates engage in Rh-catalyzed ring expansion reactions
to give 2-allyloxyfuran intermediates and that the resulting
allyloxyfurans would subsequently rearrange to Δβ,γ bu-
tenolides via a Claisen rearrangement or to the corre-
sponding ΔR,β butenolides via further Cope rearrange-
ment. For allyloxycycloprop-2-enecarboxylates with C-2
substitution, the regioselectivity can be controlled through
catalyst choice. Enantiomerically enriched butenolides can
be prepared with good levels of stereospecificity with
cyclopropenecarboxylates derived from enantiomerically
enriched allylic alcohols. Propargyl cycloprop-2-enecar-
boxylates also participate in a tandem rearrangement to
give Δβ,γ butenolides with allenic substitution.
Scheme 6. Catalyst Control over Regioselectivity
Scheme 5, a number of allylic cycloprop-2-enecarboxylate
derivatives undergo rearrangement to ΔR,β butenolides
utilizing Rh2(OPiv)4 at 110 °C in toluene. Allyl 1-phenyl-
cycloprop-2-enecarboxylate (1a), which rearranged to 2a
at 60 °C, rearranges to 5a at 110 °C. Prenyl ester 1j
undergoes spontaneous Claisen/Cope rearrangement to
give ΔR,β butenolide 5j; the Δβ,γ butenolide was not
observed. We rationalize that the ThorpeÀIngold effect
of the gem-dimethyl accelerates the rate of Cope rearran-
gement for the putative Δβ,γ butenolide intermediate. For
cycloprop-2-enecarboxylates derived from secondary allyl
alcohols, sequential ring expansion/Claisen/Cope rearran-
gements can produce diastereomers. For such substrates
(5c, 5d, 5f, 5k), the diastereoselectivity was high (g93:7).
The stereoselectivity of the tandem rearrangement is
Acknowledgment. For financial support we thank
NIGMS (GM068650). For x-ray crystallography, we
thank Glenn Yap (Delaware). NMR instrumention was
supported by NSF CHE0840401 and NIH S10RR026962.
Supporting Information Available. Full experimental
1
details, two cif files, and H and 13C NMR spectra are
provided. This material is available free of charge via the
Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 7, 2013
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