1] cycloaddition of buta-1,3-dienylcyclopropanes (BDCPs)
and CO for the synthesis of cyclooctadienones, where BDCPs
act as a C7 building block. This new [7 + 1] reaction
complements the known transition-metal-catalyzed cycload-
ditions4,5 to the synthetically challenging eight-membered
carbocyclic skeleton, which is present in many natural
products of medicinal and biological significance.6 Of the
same importance, the discovery of this new C7 building block
expands the existing set of building blocks and would create
opportunities to develop other transition-metal-catalyzed [7
+ x], [7 + x + y] cycloadditions.
Scheme 1. Previous [1,3]-Shift and Our Proposed [7 + 1]
Reaction of Buta-1,3-dienylcyclopropanes
BDCPs usually undergo [1,3]-shift reactions to give
3-vinyl-cyclopentene derivatives, either by the catalysis of
transition metals7a,b or flash vacuum pyrolysis, as the vinyl
cyclopropanes do (Scheme 1a).7c We reasoned that, under
the catalysis of Rh complex, BDCP could become a C7
building block and take part in [7 + 1] cycloaddition with
CO (Scheme 1b). In the presence of a Rh complex, BDCP
could form an η4-complex A with Rh. Then cyclopropane
cleavage gives intermediate B or C. Reductive elimination
from B to give a seven-membered carbocyclic product is
expected to be difficult since this step involves the formation
of a C(sp3)-C(sp3) bond.8 However, once CO is present,
through coordination and insertion processes, complex D or
E will be generated. Finally a migratory reductive elimination
from D or E to generate a C(sp2)-C(sp3) bond is much easier
than the reductive elimination step from B, leading to the [7
+ 1] cycloadduct F.9
and Ar (CO/Ar ) 1:9 V/V)) to 10 mol % catalyst of
[Rh(CO)2Cl]2 in dioxane.10 To our delight, this reaction really
gave the [7 + 1] cycloadduct 2a with a reaction yield of
22% (Table 1, entry 1). 2a is a conjugated cyclooctadienone11
and is probably generated from a nonconjugated cycloocta-
dienone, 3a, which is the expected [7 + 1] cycloadduct
according to the proposed mechanism shown in Scheme 1b.
This hypothesis was proved to be true by the following
experiments. First, when the partial pressure of CO was
increased to 0.5 atm, both 2a and 3a were obtained with 3a
as the minor product (Table 1, entry 2). Second, 3a can be
isomerized to 2a under the catalysis of [Rh(CO)2Cl]2 in
dioxane (Scheme 2).
To improve the [7 + 1] reaction yield, we further screened
the reaction conditions. When the CO pressure was 1.0 atm,
the [7 + 1] reaction yield was 74% with a conversion of
81% (entry 3). Further increasing the CO pressure did not
improve the reaction yield. For example, the [7 + 1] reaction
yield decreased to 57% and 45% when CO pressure was
2.0 and 4.0 atm, respectively (entries 4 and 5, Table 1).
Reducing the load of catalyst resulted in low yield (entry
6). The best solvent for the present [7 + 1] reaction is
dioxane since reactions carried out in DCE and toluene gave
lower yields (entries 7 and 8). In all cases, conjugated
cycloocta-2,4-dienone 2a is the main product, accompanied
by the minor product 3a.
We started our test of the proposed [7 + 1] reaction by
subjecting 1a and CO (balloon pressured mixed gas of CO
(4) For Rh-catalyzed cycloadditions to eight-membered rings, see: (a)
Wender, P. A.; Correa, A. G.; Sato, Y.; Sun, R. J. Am. Chem. Soc. 2000,
122, 7815. (b) Wender, P. A.; Gamber, G. G.; Hubbard, R. D.; Zhang, L.
J. Am. Chem. Soc. 2002, 124, 2876. (c) Evans, P. A.; Robinson, J. E.; Baum,
E. W.; Fazal, A. N. J. Am. Chem. Soc. 2002, 124, 8782. (d) Gilbertson,
S. R.; DeBoef, B. J. Am. Chem. Soc. 2002, 124, 8784. (e) Evans, P. A.;
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de Merjere, A.; Wender, P. A. J. Am. Chem. Soc. 2005, 127, 6530. (g)
Evans, P. A.; Baum, E. W.; Fazal, A. N.; Pink, M. Chem. Commun. 2005,
63. (h) Wender, P. A.; Christy, J. P. J. Am. Chem. Soc. 2006, 128, 5354.
(i) Wang, Y.; Wang, J.; Su, J.; Huang, F.; Jiao, L.; Liang, Y.; Yang, D.;
Zhang, S.; Wender, P. A.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 129, 10060.
(j) DeBoef, B.; Counts, W. R.; Gilbertson, S. R. J. Org. Chem. 2007, 72,
799. (k) Huang, F.; Yao, Z.-K.; Wang, Y.; Wang, Y.; Zhang, J.; Yu, Z.-X.
Chem.sAsian J. 2010, 5, 1555
.
(5) For recent other transition metal-catalyzed cycloadditions to eight-
membered rings, see: (a) Wender, P. A.; Ihle, N. J. Am. Chem. Soc. 1986,
108, 4678. (b) Wender, P. A.; Snapper, M. L. Tetrahedron Lett. 1987, 28,
2221. (c) Rigby, J. H.; Kirova-Snover, M. Tetrahedron Lett. 1997, 38, 8153.
(d) Varela, J. A.; Castedo, L.; Saa, C. Org. Lett. 2003, 5, 2841. (e) Achard,
M.; Tenaglia, A.; Buono, G. Org. Lett. 2005, 7, 2353. (f) Murakami, M.;
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P. A.; Christy, J. P. J. Am. Chem. Soc. 2007, 129, 13402. (h) Tenaglia, A.;
Gaillard, S. Angew. Chem., Int. Ed. 2008, 47, 2454. (i) Hilt, G.; Paul, A.;
Hengst, C. Synthesis 2009, 3305. (j) For other reactions, see citations in
ref 1f.
Substrate 1a, which is a mixture of the Z (1a-Z) and E
(1a-E) isomers, could not be consumed in all of the
(6) (a) Faulkner, D. J. Nat. Prod. Rep. 1988, 5, 613. (b) Daum, R. S.;
Kar, S.; Kirkpatrick, P. Nat. ReV. Drug DiscoVery 2007, 6, 865. (c) Kingston,
D. G. I. J. Org. Chem. 2008, 73, 3975.
(7) (a) Murakami, M.; Nishida, S. Chem. Lett. 1979, 927. (b) Morizawa,
Y.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1982, 23, 2871. (c) See a
recent review about the chemistry of vinylcyclopropane to cyclopentene
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4864.
(10) Low pressure of CO was found to be beneficial for some
[Rh(CO)2Cl]2-catalyzed cycloadditions such as [(5 + 2) + 1], [(3 + 2) +
1], and [(2 + 2) + 1] cycloadditions. See: (a) Kobayashi, T.; Koga, Y.;
Narasaka, K. J. Organomet. Chem. 2001, 624, 73. (b) Jiao, L.; Lin, M.;
Zhuo, L.-G.; Yu, Z.-X. Org. Lett. 2010, 12, 2528. (c) See refs 4i
and 4k.
(8) (a) Yu, Z.-X.; Wender, P. A.; Houk, K. N. J. Am. Chem. Soc. 2004,
126, 9154. (b) Yu, Z.-X.; Cheong, P. H.-Y.; Liu, P.; Legault, C. Y.; Wender,
P. A.; Houk, K. N. J. Am. Chem. Soc. 2008, 130, 2378.
1
(11) The structure of 2a was identified by H and 13C NMR of 2a and
(9) Similar intermediates were involved in [6 + 2], [5 + 2 + 1] reactions;
see refs 4a,i, and k.
confirmed by the crystallographic data of the hydrazone derivative of 2a
(see the Supporting Information).
Org. Lett., Vol. 13, No. 1, 2011
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