Cobalt-Catalyzed Carbocyclization of o-Iodobenzaldehydes and o-Iodophenylketones with Alkynes

Article abstract of DOI:10.1021/ol035514s

(Equation Presented) Treatment of various o-iodobenzaldehydes and o-iodophenyl ketones with alkynes in the presence of Co(dppe)l₂ and Zn powder in acetonitrile at 80°C afforded the corresponding indenols in moderate to excellent yields with exceedingly high regioselectivity. For most unsymmetrical alkynes tested, the carbocyclization gave a single regioisomer.

Full text of DOI:10.1021/ol035514s

ORGANIC
LETTERS
2003
Vol. 5, No. 21
3963-3966
Cobalt-Catalyzed Carbocyclization of
o-Iodobenzaldehydes and
o-Iodophenylketones with Alkynes
Kuo-Jui Chang, Dinesh Kumar Rayabarapu, and Chien-Hong Cheng*
Department of Chemistry, Tsing Hua UniVersity, Hsinchu, Taiwan 300, ROC
chcheng@mx.nthu.edu.tw
Received August 11, 2003
ABSTRACT
Treatment of various o-iodobenzaldehydes and o-iodophenyl ketones with alkynes in the presence of Co(dppe)I2 and Zn powder in acetonitrile
at 80 °C afforded the corresponding indenols in moderate to excellent yields with exceedingly high regioselectivity. For most unsymmetrical
alkynes tested, the carbocyclization gave a single regioisomer.
Transition metal-mediated transformation of aryl halides into
various organic compounds has become an exceedingly
powerful method in organic synthesis.1,2 Palladium and nickel
complexes are generally the catalysts for these reactions due
to the facile oxidative addition of aryl halides to Pd and
Ni(0) metal complexes. On the other hand, cobalt complexes
are well-known catalysts for [2 + 2 + 2]3,4 and [2 + 2]5
cycloaddition reactions, Pauson-Khand reaction,6 hydro-
formylation,7 and en-yne reductive coupling.8 The use of the
cobalt complexes as catalysts for the activation of aryl and
alkyl halides has started to draw attention only very recently.9
Oshima et al. described a cobalt-catalyzed Heck-type reaction
of alkyl halides with styrenes via a single electron-transfer
mechanism.9a Cahiez and Knochel reported cobalt-catalyzed
coupling reactions of alkenyl halides with organozinc9b and
organomagnesium9c reagents. Gosmini et al. reported the
synthesis of arylzinc compounds from aryl bromides cata-
lyzed by CoBr2 (10-20 mol %) in the presence of ZnBr2
and zinc dust.9d Activation of zinc dust by CF3COOH was
needed, and a catalytic amount of ArBr (10 mol %) was
used to avoid the formation of ArH.
Indenols10-13 are an important class of organic compounds
known for several important biological activities such as
analgesic and insecticidal properties.14,15 Palladium com-
plexes were shown to catalyze the carbocyclization of
disubstituted alkynes with o-bromobenzaldehydes and o-
(1) (a) Tsuji, J. Transition Metal Reagents and Catalysts: InnoVations
in Organic Synthesis; Wiley: New York, 2002. (b) Hegedus, L. S. Transition
Metals in the Synthesis of Complex Organic Molecules, 2nd ed.; University
Science Books: Sausalito, CA, 1999.
(2) (a) Grotjahn, D. B. In ComprehensiVe Organometallic Chemistry II;
Hegedus, L. S., Ed.; Pergamon/Elsevier Science: Kidlington, 1995; Vol
12, pp 703, 741. (b) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996,
96, 49. (c) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem.
ReV. 1996, 96, 635. (d) Fruhauf, H. W. Chem. ReV. 1997, 97, 523.
(3) (a) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539.
(b) Grotjahn, D. B.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1986, 108, 2091.
(c) Butenschon, H.; Winkler, M.; Vollhardt, K. P. C. Chem. Commun. 1986,
388. (d) Johnson, E. P.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1991, 113,
381.
(7) (a) Zieglar, T.; Versluis, L. AdV. Chem. Ser. 1992, 230, 75. (b) Slaugh,
L. H.; Mullineaux, R. D. J. Organomet. Chem. 1968, 13, 469.
(8) Wang, C. C.; Lin, P. S.; Cheng, C. H. J. Am. Chem. Soc. 2002, 124,
9696.
(4) Wu, M. S.; Shanmugasundaram, M.; Cheng, C. H. Chem. Commun.
2003, 718.
(5) Chen, K. C.; Rayabarapu, D. K.; Wang, C. C.; Cheng, C. H. J. Org.
Chem. 2001, 66, 8804.
(6) (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman,
M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977. (b) Pauson, P. L.
Tetrahedron 1985, 41, 5855. (c) Khand, I. U.; Pauson, P. L. J. Chem. Soc,
Chem. Commun. 1974, 379.
(9) (a) Ikeda, Y.; Nakamura, T.; Yorimtsu, H.; Oshima, K. J. Am. Chem.
Soc. 2002, 124, 6514. (b) Cahiez, G.; Avedissian, H. Tetrahedron Lett.
1998, 39, 6159. (c) Avedissian, H.; Berillon, L.; Cahiez, G.; Knochel, P.
Tetrahedron Lett. 1998, 39, 6163. (d) Fillon, H.; Gosmini, C.; Perichon, J.
J. Am. Chem. Soc. 2003, 125, 3867. (e) Gomes, P.; Gosmini, C.; Perichon,
J. Org. Lett. 2003, 5, 1043.
10.1021/ol035514s CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/10/2003

1
bromophenyl ketones to give indenols.12 We also reported
that nickel complexes exhibit similar catalytic properties for
the carbocyclization of propiolates with o-iodophenyl ke-
tones.16 Our interest in cobalt-catalyzed reactions4,5,8 and the
recent attention of activation of aryl halides by complexes
of the cobalt family9 have prompted us to investigate the
catalytic activity of cobalt complexes for the carbocyclization
of o-iodobenzaldehydes and o-iodophenyl ketones with
alkynes. Herein, we report for the first time that cobalt
phosphine complexes successfully catalyze the reaction under
mild conditions to afford indenol derivatives with excellent
regioselectivity and in high yields. Surprisingly, the present
cobalt catalyst system is more competitive than the palladium
and nickel system for the synthesis of indenols. This result
opens a new direction for the activation of Ar-X bond with
cobalt complexes.
structure of 3a was established on the basis of its H and
13C NMR and mass data. Control experiments indicated that
in the absence of either Co(dppe)I2 or zinc metal, no desired
product was observed in the reaction.
Similarly, various iodobenzaldehydes (1a-c) and alkynes
(2a-e) undergo carbocyclization in the presence of
Co(dppe)I2 and zinc powder to give the corresponding
indenols 3a-h in 54∼85% yields. A small amount of
reduction products o-iodobenzyl alcohols was observed for
these reactions. The results are summarized in Table 1
(entries 1-8). For unsymmetrical alkynes, the regioselectivity
is generally excellent. Two regioisomers 3e and 3e′ with a
ratio of 88/12 were obtained for 1-phenyl-1-hexyne, but only
one regioisomer was detected for MeCtCTMS (2d, entry
6) and PhCtCTMS (2e, entries 7-8). The regiochemistry
of these products as shown in Table 1 was carefully assigned
on the basis of NOE experiments. The major isomer 3e from
1a and 2c has the phenyl group next to the hydroxy moiety,
while for products 3f-h, the TMS group is away from the
hydroxy moiety.
The reaction of 2-iodobenzaldehyde (1a) with diphenyl-
acetylene (2a) in the presence of Co(PPh3)2I2 and zinc metal
powder in acetonitrile at 80 °C for 3 h proceeded to give
indenol 3a in 22% yield (Scheme 1). The yield of 3a was
The carbocyclization of o-iodophenyl ketones with alkynes
also proceeds smoothly to furnish the corresponding indenols.
As shown in Table 1 (entires 9-19), the reaction of
2-iodoacetophenone (2d) with alkynes 2a-g afforded the
corresponding indenols 3i-p in excellent yields. The car-
bocyclization of 2d with unsymmerical alkynes is highly
regioselective. For alkyne 2c, regioisomers 3k/3k′ were
obtained in a 89/11 ratio, while for trimethylsilyl alkynes
2d and 2e, only one regioisomer was found. The regiochem-
istry of 3k-m is similar to that of o-iodobenzaldehyde
reaction. For propiolates 2g and 2h, the cyclization also
proceeds smoothly to afford single regioisomers 3o and 3p,
respectively (Table 1). Similarly, the reaction of substituted
iodophenyl ketones 1e-g with 2a produced substituted
indenol in good to excellent yields (entries 17-19).
Scheme 1
Scheme 2
greatly improved to 85%, when Co(dppe)I2 (dppe ) bis-
(diphenylphosphino)ethane) was used as the catalyst. The
(10) For other methods of indenol synthesis, see: (a) Liebeskind, L. S.;
Gasdaska, J. R.; MaCallum, J. S.; Tremont, S. J. J. Org. Chem. 1989, 54,
669. (b) Cambie, R. C.; Metzler, M. R.; Rutledge, P. S.; Woodgate, P. D.
J. Organomet. Chem. 1990, 381, C26. (c) Cambie, R. C.; Metzler, M. R.;
Rutledge, P. S.; Woodgate, P. D. J. Organomet. Chem. 1990, 398, C22.
(d) Robinson, N. P.; Main, L.; Nicholson, B. K. J. Organomet. Chem. 1989,
364, C37.
(11) (a) Vicente, J.; Abad, J.-A.; Gil-Rubio, J. J. Organomet. Chem. 1992,
436, C9. (b) Vicente, J.; Abad, J. A.; Rubio, J. G. Organometallics 1996,
15, 3509. (c) Vicente, J.; Abad, J. A.; Lopez-Pelaez, B.; Martinez-Pivente,
E. Organometallics 2002, 21, 58.
(12) (a) Quan, L. G.; Gevorgyan, V.; Yamamoto, Y. J. Am. Chem. Soc.
1999, 121, 3545. (b) Quan, L. G.; Gevorgyan, V.; Yamamoto, Y. J. Am.
Chem. Soc. 1999, 121, 9485. (c) Quan, L. G.; Gevorgyan, V.; Yamamoto,
Y. Tetrahedron Lett. 1999, 40, 4089.
(13) Larock, R. C.; Doty, M. J.; Cachi, S. C. J. Org. Chem. 1993, 58,
4579.
(14) (a) Kurakay Co., Ltd. Jpn. Kokai Tokkyo Koho JP 81, 113, 740
(C1.C07C69/017), Sept 7, 1981; Chem. Abstr. 1982, 96, 68724b. (b)
Kurakay Co., Ltd. Jpn. Kokai Tokkyo Koho JP 82 04,945 (C1. C07C69/
013), Jan 11, 1982; Chem. Abstr. 1982, 96, 199935u.
(15) Samula, K.; Cichy, B. Acta Pol. Pharm. 1985, 42, 256; Chem. Abstr.
1986, 105, 171931v.
(16) Rayabarapu, D. K.; Cheng, C.-H. Chem. Commun. 2002, 942.
3964
Org. Lett., Vol. 5, No. 21, 2003

Table 1. Results of Cobalt-Catalyzed Carbocyclization of o-Iodobenzaldehydes and Iodophenyl Ketone (1) with Alkynes (2)a
a Reaction conditions: o-iodobenzaldehyde or o-iodophenyl ketone (1.00 mmol), alkyne (1.50 mmol), Co(dppe)I2 (0.050 mmol; 5.0 mol %), Zn (2.75
mmol), CH3CN (3.0 mL) at 80 °C for 3 h. b Isolated yields; isomeric ratios are in parentheses.
Compared with the corresponding palladium- and nickel-
catalyzed reactions, the present cobalt-catalyzed carbo-
cyclization shows several advantages. The reactions condi-
tions are mild, and a very short reaction time (only 3 h) is
needed for completion. Moreover, the yields are generally
excellent (entries 9-19) and obtained with very high
regioselectivity for the unsymmetrical alkynes used.
The exact mechanism for the present catalytic reaction is
not yet clear, but on the basis of the known cobalt chemistry,
the following pathway (Scheme 2) is proposed. Reduction
of Co(II) to Co(I) by zinc dust initiates the catalysis.
Oxidative addition of o-iodobenzaldehyde to Co(I) species
affords an o-metalated benzaldehyde cobalt complex 4 with
both the o-carbon and the aldehyde oxygen bonded to the
cobalt(III) center. Intermediate 4 undergoes insertion with
an alkyne to generate a seven-membered cobaltacycle 5.
Intramolecular nucleophilic addition of the cobalt-carbon
bond in 5 to the aldehyde group leads to the formation of
cobalt alkoxide 6. Reduction of the latter by zinc powder
affords a Co(I) alkoxide 7. Transmetalation of 7 with ZnI2
generates the active Co(I) species and the corresponding zinc
alkoxide 8, which is converted to the final product 3 after
hydrolysis. Oxidative addition of aryl halides to cobalt(I) has
been proposed in a cobalt-mediated reaction,9d although no
such oxidative additon product has been isolated previously.
An alternative pathway involving the reduction of Co(III)
species 4 by zinc metal to Co(I) intermediate 9, followed
by insertion of an alkyne to give 10, cannot be totally
excluded.
In summary, we have demonstrated that the Co(dppe)I2/
Zn system successfully catalyzed the carbocyclization reac-
tion of o-iodobenzaldehydes and o-iodophenyl ketones with
Org. Lett., Vol. 5, No. 21, 2003
3965

alkynes to afford indenols in high regioselectivity and
excellent yields. The cobalt system appears to be more
efficient than the palladium and nickel catalysts for this
carbocyclization reaction. The success of this cobalt-
catalyzed carbocyclization certainly will encourage more
research on the reaction of aryl or alkenyl halides with
unsaturated carbon-carbon bonds using complexes of the
cobalt family as the catalyst. Further work in this direction
is underway.
Acknowledgment. We thank the National Science Coun-
cil of Republic of China (NSC 91-2113-M-007-053) for the
support of this research.
Supporting Information Available: Preparation details,
characterization data, and 1H NMR spectra of all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL035514S
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Org. Lett., Vol. 5, No. 21, 2003