The 2-bromo-3-exo-methylenecycloalkenes 3a-f obtained
here were applied in the Pd-catalyzed reaction with a soft
nucleophile. It was found that a series of endocyclic allenes
5 could be prepared and isolated in excellent yields (88-98%)
as persistent species when the size of the carbocycles was
nine or larger. The results of the Pd-catalyzed reaction for
3a-d are summarized in Table 1. The cyclic bromide 3a
A reaction of 3e with 4m under the same conditions as in
Table 1 was somewhat slower and needed a longer reaction
time (36 h) until total consumption of 3e. Although initial
formation of the eight-membered cyclic allene 5em could
be confirmed by various NMR measurements (a characteristic
long-range coupling between the vinyl H and -CH2Nu with
1
5JHH ) 1.7 Hz in the H NMR spectrum; a 13C NMR
resonance of the allenic central sp-C in the low field at δ
204.2), it was not stable and was slowly converted to an
isomeric mixture of homodimers in a few hours (ca. 70%
yield, Scheme 3).11,12 The structure of the major isomer 6
Table 1. Palladium-Catalyzed Preparation of Endocyclic
Allenesa
Scheme 3
entry substrate 3 H-Nu 4 time (h) product yield (%)b
1
2
3
4
5
6
7
8
9
3a (n ) 12)
3a (n ) 12)
3b (n ) 9)
3b (n ) 9)
3b (n ) 9)
3c (n ) 7)
3d (n ) 6)
3d (n ) 6)
3d (n ) 6)
4m
4n
4m
4n
4o
4m
4m
4n
4o
12
48
12
24
48
12
14
48
72
5am
5an
5bm
5bn
5bo
5cm
5dm
5dn
5do
92
93
95
98
97
94
98
88
89
was unambiguously determined as shown in Scheme 3 by
an X-ray analysis (see Supporting Information).
On the other hand, the seven-membered cyclic substrate
3f was inert to the Pd-catalyzed reaction with 4m under the
identical conditions and remained unchanged.
As shown in Figure 1, unique stereoselectivity was
expected in reactions of the endocyclic allenes 5 by the
shielding effect of the polymethylene chains connecting the
two allenic termini. To examine this possibility, the 12-, 10-,
and 9-membered endocyclic allenes (5bm, 5 cm, and 5dm)
were applied to [2 + 2]cycloaddition reactions with
ketenes.13,14 Reactions of an acyclic allene 7 were also
examined for comparison. The results are summarized in
Table 2.
A reaction of the acyclic allene 7 with dichloroketene (8x)
proceeded at 23 °C to give 9x in 57% yield as a mixture of
four isomers in a 61:12:24:3 ratio (Table 2, entry 1).
Similarly, a reaction between 5bm and 8x afforded a mixture
of four isomeric products (entry 2). Apparently, the 12-
membered carbocycle in 5bm is too large to display the
expected stereochemical control. The smaller-membered
cyclic allenes, however, exhibited the stereoselectivity in the
[2 + 2]cycloaddition. A product from 5cm and 8x consisted
a The reaction was carried out at 40 °C in THF in the presence of the
palladium catalyst (2 mol %) generated from [PdCl(η3-C3H5)]2 and dpbp.
b Isolated yields.
was reacted with CHMe(CO2Me)2 (4m) and NaH in THF in
the presence of a Pd catalyst (2 mol %) generated in situ
from [PdCl(η3-C3H5)]2 and dpbp9 to give the corresponding
endocyclic allene 5am in 92% yield (Table 1, entry 1). A
variety of nucleophiles, such as stabilized carbanions (4m
and 4n) and an N-nucleophile (4o), could be used for the
present reactions.
The (E)/(Z)-geometry in 3 is not critical for the Pd-
catalyzed reaction.10 A Pd-catalyzed reaction between 3c
(E/Z ) 96/4) and 4m was terminated prior to its completion
(ca. 80% conversion), and unreacted 3c was recovered from
the reaction mixture. An 1H NMR analysis revealed that the
recovered 3c was also a mixture of the two isomers with
E/Z ) 93/7. Indeed, both the substrates with (Z)-configuration
(3a and 3b; entries 1-5) and those with (E)-configuration
(3c and 3d; entries 6-9) reacted with 4 smoothly under
palladium catalysis to give 5 in equally good yields. In all
cases, the reactions proceeded cleanly, and no appreciable
byproducts were detected in the reaction mixtures.
(11) Jacobs, T. L.; McClenon, J. R.; Muscio, O. J., Jr. J. Am. Chem.
Soc. 1969, 91, 6038.
(12) A kinetically stabilized eight-membered endocyclic allene was
reported, see: Price, J. D.; Johnson, R. P. Tetrahedron Lett. 1986, 27, 4679.
(13) (a) Brady, W. T. In The Chemistry of Ketenes, Allenes, and Related
Compounds; Patai, S., Ed.; Wiley: Chichester, 1980; p 298. (b) Coppola,
G. M.; Schuster, H. F. Allenes in Organic Synthesis; Wiley: New York,
1984; p 291. (c) Hopf, H. In The Chemistry of the Allenes; Landor, S. R.,
Ed.; Academic Press: London, 1982; p 525. (d) Runge, W. In The Chemistry
of the Allenes; Landor, S. R., Ed.; Academic Press: London, 1982; p 663.
(e) Tidwell, T. T. Ketenes, 2nd ed.; Wiley: NJ, 2006; p 492.
While the compounds 3a-d are excellent precursors to
the endocyclic allenes in the Pd-catalyzed reaction, the
smaller carbocycles 3e and 3f show different reactivity.
(14) (a) Weyler, W., Jr.; Byrd, L. R.; Caserio, M. C.; Moore, H. W.
J. Am. Chem. Soc. 1972, 94, 1027. (b) Bertrand, M.; Gras, J.-L.; Gore´, J.
Tetrahedron Lett. 1972, 13, 2499. (c) Duncan, W. G., Jr.; Moore, H. W.
Tetrahedron Lett. 1973, 14, 4391. (d) Brady, W. T.; Stockton, J. D.; Patel,
A. D. J. Org. Chem. 1974, 39, 236. (e) Bertrand, M.; Maurin, R.; Gras,
J. L.; Gil, G. Tetrahedron 1975, 31, 849.
(9) dpbp ) 2,2′-bis(diphenylphosphino)-1,1′-biphenyl. See: Ogasawara,
M.; Yoshida, K.; Hayashi, T. Organometallics 2000, 19, 1567.
(10) Ogasawara, M.; Okada, A.; Watanabe, S.; Fan, L.; Uetake, K.;
Nakajima, K.; Takahashi, T. Organometallics 2007, 26, 5025.
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