Table 1. Optimization of Reaction Conditionsa
Scheme 1
entry
catalyst
solventb
3a yield
[%]
1
2
3
Ni(PPh3)2Cl2
Ni(PPh3)2Br2
Ni(PPh3)2I2
THF
THF
THF
trace
5
8
(a) arylnickel species undergoes intramolecular transmetal-
ation9a to form a nickelacyclobutabenzene,9b-d which would
undergo alkyne coordination10 and subsequent alkyne inser-
tion to afford indene; (b) arylnickel coordination to alkyne
and subsequent insertion4 of the alkyne would form a vinylic
nickel intermediate, which would undergo intramolecular
transmetalation and subsequent reductive elimination to give
an indene product. Thus both pathways a and b could be
regarded as interrupted INC reactions.
4
5
6
7
8
9
10
11
12
13
14
15
Ni(PPh3)2I2
Ni(PPh3)2I2
Ni(PPh3)2I2
Ni(PPh3)2I2
Ni(PPh3)2I2/2PPh3
Pd(PPh3)2Cl2
Ni(acac)2
Ni(dppe)I2
NiPy2Cl2
CH3CN
DMF
trace
trace
trace
82
17
3
4
2
6
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Since Ni(II) could be easily reduced to a Ni(0) species by
benzylzinc reagent,11 we initiated our efforts by employment
of air stable Ni(PPh3)2X2 (X ) Cl, Br, I).12 As shown in
Table 1, phenylacetylene 2a was used as the model substrate,
and various Ni species and solvents were investigated to
increase the yield (Table 1).
Ni{P(p-MeOC6H4)3}2Cl2
Ni(PPh3)4
Ni(PPh3)2I2/Zn
10
31
17
a The reaction was carried out by the addition of 3.5 equiv of Zinc reagent
to a solution of 1.0 equiv of alkyne and 0.1 equiv of Ni catalyst in different
solvents, and yield was calculated based on GC with acetophenone as an
internal standard. b All reactions were conducted at refluxing temperature
of solvents except DMF (at 80 °C) and toluene (at 80 °C).
Among various Ni(II) species and solvents investigated
(Table 1, entries 1-7, 10-13), Ni(PPh3)2I2 in CH2Cl213 was
found to be the most reactive (Table 1, entry 7). Ni(PPh3)2I2
is more effective than Ni(PPh3)2Cl2 and Ni(PPh3)2Cl2 prob-
ably because iodide coordination could stabilize either Ni-
(0) or Ni(II) species as Percec addressed.12d Although
solvents such as THF, DMF, and CH3CN are frequently used
in the intermolecular Negishi reaction, each of them is
ineffective toward this INC-type reaction. A bidentate ligand
(dppe) is not favorable for increasing the reactivity of the
Ni catalyst (Table 1, entry 11). The addition of 0.2 equiv of
PPh3 to the reaction disfavored the carboannulation reaction
(Table 1, entry 8).
The employment of Pd(PPh3)2Cl2 gave a low yield of 3a
(Table 1, entry 9). The Ni(0) species such as Ni(PPh3)4only
gave 3a in 31% yield (Table 1, entry 14). Other Ni(0) species
from the reduction of Ni(PPh3)2I2 by zinc dust also afforded
3a in low yield (Table 1, entry 15).
Control experiments indicated that no desired product was
observed in the absence of Ni(PPh3)2I2.
(9) (a) Bennett, M. A.; Hambley, T. W.; Roberts, N. K.; Robertson, G.
B. Organometallics 1985, 4, 1992. (b) Neidlein, R.; Rufinska, A.; Schwager,
H.; Wilke, G. Angew. Chem., Int. Ed. Engl. 1986, 25, 640. (c) Kru¨ger, C.;
Laakmann, K.; Schroth, G.; Schwager, H.; Wilke, G. Chem. Ber. 1987,
120, 471. (d) Schwager, H.; Benn, R.; Wilke, G. Angew. Chem., Int. Ed.
Engl. 1987, 26, 67.
(10) (a) Campora, J.; Llebaria, A.; Moreto, J. M.; Poveda, M. L.;
Carmona, E. Organometallics 1993, 12, 4032. (b) Carmona, E.; Gutierrez-
Puebla, E.; Marh, J. M.; Monge, A.; Paneque, M.; Poveda, M. L.; Ruiz, C.
J. Am. Chem. Soc. 1989, 111, 2883. (c) Carmona, E.; Palma, P.; Paneque,
M.; Poveda, M. L.; Gutierrez-Puebla, E.; Monge, A. J. Am. Chem. Soc.
1986, 108, 6424. (d) Campora, J.; Gutierrez-Puebla, E.; Monge, A.; Palma,
P.; Poveda, M. L.; Ruiz, C.; Carmona, E. Organometallics 1994, 13, 1728.
(e) Campora, J.; Carmona, E.; Gutierrez-Puebla, E.; Poveda, M. L.; Ruiz,
C. Organometallics 1988, 7, 2577.
(11) (a) Wu, J.; Yang, Z. J. Org. Chem. 2001, 66, 7875. (b) Srogl, J.;
Liu, W.; Marshall, D.; Liebeskind, L. S. J. Am. Chem. Soc. 1999, 121,
9449. (c) Wu, J.; Sun, X.; Zhang, L. Chem. Lett. 2005, 34, 796. (d) Krapcho,
A. P.; Gilmor, T. R. J. Heterocycl. Chem. 1999, 36, 445.
(12) (a) Venanzi, L. M. J. Chem. Soc. 1958, 719. (b) Kanai, H.; Sakaki,
S.; Sakatani, T. Bull. Chem. Soc. Jpn. 1987, 60, 1589. (c) Dunstan, P. O.
Thermochim. Acta 2005, 437, 100. (d) Percec, V.; Bae, J.; Zhao, M.; Hill,
D. H. J. Org. Chem. 1995, 60, 176.
With optimized reaction conditions in hand, we explored
the scope and limitation of this method (Table 2). All
1-arylacetylenes underwent carboannulation reaction with 1
to give 2-arylindene products in high regioselectivities and
good yield regardless of the nature and the position of the
substituents (Table 2, entries 1-6). 1-Naphthyl acetylene
could also react with 1 to afford indene 3g in good
regioselectivities (Table 2, entry 7). As entry 8 demonstrates,
this transformation tolerates internal alkenes. 1-Alkyl acety-
lenes gave the desired 2-alkyl indene products under identical
reaction conditions (Table 2, entries 9, 10). The reaction of
1 with symmetrical alkynes such as diphenylacetylene
afforded the desired product in 76% yield (Table 2, entry
11). The annulation process is regioselective for internal
alkynes containing TMS, yielding the regioisomers with the
more sterically demanding TMS group in the 2 position of
the indene ring (Table 2, entries 13, 14). In the reaction of
2l, two regioisomers 3l and 3l′ were obtained in the ratio of
3/1, and the major isomer 3l again has the more bulky phenyl
group in the 2-position of the indene ring (Table 2, entry
12). In the case of 2o, product 3o has the COOMe in the
(13) (a) After 1 was prepared in THF as in ref 8, the THF was removed
by concentration in vacuo. The remaining gray solid was dissolved in dry
CH2CI2. See: Yanagisawa, A.; Habaue, S.; Yamamoto, H. J. Am. Chem.
Soc. 1989, 111, 366. (b) On the basis of GC and NMR analysis, 62% of 1
in entry 7 (Table 1) was converted to 9,10-dihydroanthracene via intermo-
lecular Negishi coupling reaction and 4% of 1 was converted to 9,10-
dihydrophenanthrene.
5208
Org. Lett., Vol. 9, No. 25, 2007