the alkyne (R1) in the reaction with phenylzinc chloride
(entries 1-6). With respect to the nucleophilic component,
not only various arylzinc chlorides (entries 7-10) but also
methylzinc chloride (entry 11) provide the desired products
in high yield (75-80% yield).9
Table 1. Rhodium-Catalyzed Phenylation-Cross-Coupling
Reaction of 1a:Ligand Effect
With regard to the reaction mechanism, path A is generally
believed for the palladium-catalyzed analogous processes
(Scheme 1).5c Thus, initial oxidative addition of the iodoarene
entry
ligand
yield (%)a
1b
2
3
cod
17
13
13
87c
Scheme 1. Catalytic Cycle for the Palladium-Catalyzed
Formation of Compound 2 (path A) and Proposed Catalytic
Cycle for the Rhodium-Catalyzed Formation of Compound 2
(path B)
dppp
dppb
dppf
4
a Determined by 1H NMR against an internal standard (MeNO2).
b [RhCl(cod)]2 was used as a catalyst. c Isolated yield.
We subsequently discovered that the reaction progress is
highly dependent on the ligand employed. Thus, the use of
dppp or dppb as a ligand resulted in low yield of 2a (13%
yield; entries 2 and 3), but the employment of dppf (1,1′-
bis(diphenylphoshphino)ferrocene)6 dramatically improved
the reactivity, furnishing 2a in 87% yield (entry 4).7
Under these conditions with dppf as the ligand, the scope
of this reaction is illustrated in Table 2.8 The catalyst loading
Table 2. Rhodium-Catalyzed Arylation-Cross-Coupling
Reaction of 1: Scope
entry
product
yield (%)a
1
2b
3
4
5
6
7
8
9
R1 ) n-Bu, R2 ) Ph (2a)
87
78
84
94
57
85
77
80
78c
77
75
R1 ) n-Bu, R2 ) Ph (2a)
of substrate 1 to palladium(0) generates arylpalladium(II)
intermediate A1. Intramolecular insertion of the alkyne to
this carbon-palladium bond affords alkenylpalladium(II)
species A2. Subsequent transmetalation of the aryl group
gives bis(organo)palladium(II) A3, and reductive elimination
releases product 2 to regenerate the palladium(0) complex.
One can propose a similar mechanism for the present
rhodium catalysis just by changing Pd(0)/Pd(II) to Rh(I)/
R1 ) (CH2)3OMe, R2 ) Ph (2b)
R1 ) i-Bu, R2 ) Ph (2c)
R1 ) i-Pr, R2 ) Ph (2d)
R1 ) Ph, R2 ) Ph (2e)
R1 ) n-Bu, R2 ) 3-MeOC6H4 (2f)
R1 ) n-Bu, R2 ) 3-MeC6H4 (2g)
R1 ) n-Bu, R2 ) 3-ClC6H4 (2h)
R1 ) n-Bu, R2 ) 4-MeOC6H4 (2i)
R1 ) n-Bu, R2 ) Me (2j)
10
11
(4) For recent reviews, see: (a) Negishi, E., Ed. Handbook of Organo-
palladium Chemistry for Organic Synthesis; John Wiley & Sons: Hoboken,
NJ, 2002; Vol. 1. (b) Netherton, M. R.; Fu, G. C. In Topics in
Organometallic Chemistry: Palladium in Organic Synthesis; Tsuji, J., Ed.;
Springer: New York, 2005; p 85.
a Isolated yield. b The reaction was conducted with 3 mol % catalyst
loading. c Contaminated with ∼5% impurity.
(5) (a) Cheung, W. S.; Patch, R. J.; Player, M. R. J. Org. Chem. 2005,
70, 3741. (b) Yanada, R.; Obika, S.; Inokuma, T.; Yanada, K.; Yamashita,
M.; Ohta, S.; Takemoto, Y. J. Org. Chem. 2005, 70, 6972. (c) D’Souza, D.
M.; Rominger, F.; Mu¨ller, T. J. J. Angew. Chem., Int. Ed. 2005, 44, 153.
(d) Couty, S.; Lie´gault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511.
See also: (e) Yanada, R.; Obika, S.; Oyama, M.; Takemoto, Y. Org. Lett.
2004, 6, 2825.
(6) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158.
(7) The reaction can be conducted in other solvents with similar efficiency
(72% yield in THF, 86% yield in DME, 78% yield in toluene, and 75%
yield in dichloromethane).
can be lowered to 3 mol % with minimal decrease of the
yield (78% yield; entry 2). Primary and secondary alkyl
groups as well as aryl groups can be used as substituents on
(3) (a) Hossain, K. M.; Takagi, K. Chem. Lett. 1999, 1241. (b) Takahashi,
H.; Hossain, K. M.; Nishihara, Y.; Shibata, T.; Takagi, K. J. Org. Chem.
2006, 71, 671. (c) Takahashi, H.; Inagaki, S.; Nishihara, Y.; Shibata, T.;
Takagi, K. Org. Lett. 2006, 8, 3037. (d) Ueura, K.; Satoh, T.; Miura, M.
Org. Lett. 2005, 7, 2229. See also: (e) Yasui, H.; Mizutani, K.; Yorimitsu,
H.; Oshima, K. Tetrahedron 2006, 62, 1410.
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Org. Lett., Vol. 8, No. 21, 2006