Carbocycle synthesis via carbopalladation of nitriles [11]

Full text of DOI:10.1021/ja984086w

3238
J. Am. Chem. Soc. 1999, 121, 3238-3239
Scheme 1
Carbocycle Synthesis via Carbopalladation of Nitriles
Richard C. Larock,* Qingping Tian, and Alexandre A. Pletnev
Department of Chemistry, Iowa State UniVersity
Ames, Iowa 50011
ReceiVed NoVember 30, 1998
Et3N, and 9:1 DMF-water as the solvent at 130 °C for 24 h.
The extraordinary utility of palladium in organic synthesis in
recent years is due in large part to the unique ability of palladium
to form carbon-carbon bonds without protecting most important
functional groups.1 Thus, alcohols, amines, aldehydes, ketones,
carboxylic acids, and derivatives are generally readily accom-
modated by organopalladium intermediates under conditions
where carbon-carbon bond formation is facile. There are also a
number of examples of simple ortho- and para-substituted
aromatic nitriles readily undergoing palladium-catalyzed processes
without involvement of the nitrile functionality.2 In fact, palladium
chloride bis-acetonitrile and bis-benzonitrile are widely used
reagents and acetonitrile is one of the most commonly employed
solvents in organopalladium chemistry. In exploring the scope
of the hetero- and carboannulation of alkenes, dienes, and
alkynes,3 we have recently observed that simple nitrile groups
can actively participate in these annulation processes when the
carbopalladation step involved is intramolecular.4 We report here
our preliminary observations on the synthesis of carbocycles via
carbopalladation of nitriles.
This process appears to involve arylpalladium formation and
subsequent alkyne insertion to produce a vinylic palladium
intermediate, which then adds across the carbon-nitrogen triple
bond of the nitrile to produce a palladium imine intermediate,
which hydrolyzes to the corresponding ketone (Scheme 1).
Subsequent reduction of the palladium(II) salt produced is required
to afford a catalytic process. Presumably, the triethylamine
employed by us is effecting this reduction.
This chemistry appears to be quite general, since we have found
that the analogous chemistry of 2-o-iodophenyl-2-methyl-
propanenitrile and diphenylacetylene affords high yields of the
expected six-membered ring aromatic ketone (eq 2), by what is
assumed to be an analogous mechanism.
We have recently reported that the carboannulation of internal
alkynes by o-iodobenzaldehyde provides a useful new synthetic
approach to indenones.3c In exploring the palladium chemistry
of o-iodobenzonitrile, we have made the unusual observation that
this substrate will undergo facile carboannulation of diphenyl-
acetylene to afford high yields of the corresponding 2,3-
diphenylindenone (eq 1). The best reaction conditions thus far
observed employ 10% Pd(dba)2, 3 equiv of alkyne, 1 equiv of
When o-iodophenylacetonitrile was employed instead of 2-o-
iodophenyl-2-methylpropanenitrile, we were surprised to find that
high yields of â-naphthylamines were obtained instead (eq 3).
(1) (a) Tsuji, J. Palladium Reagents and Catalysts: InnoVations in Organic
Synthesis: InnoVations in Organic Synthesis; John Wiley & Sons: New York,
1995. (b) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: New York, 1985.
(2) (a) Sakampto, T.; Shiga, F.; Yasuhara, A.; Uchiyama, D.; Kondo, Y.;
Yamanaka, H. Synthesis 1992, 746. (b) Bumagin, N. A.; Sukhomlinova, L.
L.; Luzikova, E.; Tolstaya, T. P.; Beletskaya, I. P. Tetrahedron Lett. 1996,
37, 897. (c) Kanai, G.; Miyaura, N.; Suzuki, A. Chem. Lett. 1993, 845. (d)
Sakamoto, T.; Kondo, Y.; Yamanaka, H. Chem. Pharm. Bull. 1985, 33, 626.
(3) (a) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689. (b)
Larock, R. C.; Yum, E. K.; Doty, M. J.; Sham, K. K. C. J. Org. Chem. 1995,
60, 3270. (c) Larock, R. C.; Doty, M. J.; Cacchi, S. J. Org. Chem. 1993, 58,
4579. (d) Larock, R. C.; Fried, C. A. J. Am. Chem. Soc. 1990, 112, 5882. (e)
Larock, R. C.; Berrios-Pen˜a; N.; Narayanan, K. J. Org. Chem. 1990, 55, 3447.
(f) Larock, R. C.; Yum, E. K. Synlett 1990, 529. (g) Larock, R. C.; Berrios-
Pen˜a, N. G.; Fried, C. A. J. Org. Chem. 1991, 56, 2615. (h) Larock, R. C.;
Berrios-Pen˜a, N. G.; Fried, C. A.; Yum, E. K.; Tu, C.; Leong, W. J. Org.
Chem. 1993, 58, 4509. (i) Larock, R. C.; Zenner, J. M. J. Org. Chem. 1995,
60, 482. (j) Larock, R. C.; Guo, L. Synlett 1995, 465. (k) Larock, R. C.; Yum,
E. K.Tetrahedron 1996, 52, 2743. (l) Larock, R. C.; Doty, M. J.; Tian, Q.;
Zenner, J. M. J. Org. Chem. 1997, 62, 7536. (m) Larock, R. C.; Tian, Q. J.
Org. Chem. 1998, 63, 2002. (n) Larock, R. C.; He, Y.; Leong, W. W.; Han,
X.; Refvik, M. D.; Zenner, J. M. J. Org. Chem. 1998, 63, 2154. (o) Larock,
R. C.; Doty, M. J.; Han, X. Tetrahedron Lett. 1998, 39, 5143. (p) Larock, R.
C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39, 5713. (q) Roesch, K. R.;
Larock, R. C. J. Org. Chem. 1998, 63, 5306. (r) Larock, R. C.; Tu, C.; Pace,
P. J. Org. Chem. 1998, 63, 6859. (s) Larock, R. C.; Yum, E. K.; Refvik, M.
D. J. Org. Chem. 1998, 63, 7652. (t) English, D. S.; Das, K.; Zenner, J. M.;
Zhang, W.; Kraus, G. A.; Larock, R. C.; Petrich, J. W. J. Phys. Chem. 1997,
101, 3235.
Our best present reaction conditions for this process involve 5
mol % Pd(OAc)2, 3 equiv of alkyne, 2 equiv of Et3N, and 1 equiv
of n-Bu4NCl in DMF at 100 °C for 48 h. This afforded an 83%
yield of 2-amino-3,4-diphenylnaphthalene from diphenylacetylene.
1-Phenylpropyne and 3,3-dimethyl-2-butyne (5 equiv of alkyne
and 2 equiv of water were added) afforded 65 and 75% yields,
respectively, of the corresponding â-naphthylamines in which the
bulkier substituent of the alkyne resides exclusively in the
3-position, as noted in all of our previous annulation chemistry.3
This particularly convenient synthesis of hindered â-naphthyl-
amines affords readily available starting materials for the synthesis
of 2,2′-diamino-1,1′-binaphthyls, substrates proving increasingly
useful as ligands in organic chemistry (eq 4).5
(4) For prior examples of the arylpalladium of potentially chelating
R-aminonitriles leading to fragmentation or electrocyclization, see: (a) Yang,
C.-C.; Sun, P. J.; Fang, J.-M. J. Chem. Soc., Chem. Commun. 1994, 2629. (b)
Yang, C.-C.; Tai, H.-M.; Sun, P.-J. Synlett 1997, 812. (c) Yang, C.-C.; Tai,
H.-M., Sun, P.-J. J. Chem. Soc, Perkin Trans. 1 1997, 2843.
10.1021/ja984086w CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/19/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 13, 1999 3239
It appears that a similar alkyne/nitrile carbopalladation process
is involved in this synthesis of â-naphthylamines but that the
intermediate palladium imine is undergoing tautomerization before
hydrolysis, resulting in the amine products, rather than ketones.
Presumably, tautomerization and reduction of the palladium(II)
salt are again being effected by the triethylamine present in the
reaction. It is noteworthy, however, that the yields of â-naph-
thylamines are substantially lower if the solvent DMF is replaced
by other polar solvents, such as DMA, DMSO, or acetonitrile.
Thus, the solvent may also be playing a key role in reducing the
palladium.
Scheme 2
When 4-octyne (5 equiv) was employed as the acetylene, the
yield of product dropped substantially, but to our surprise, the
major product obtained in 30% yield was 2-amino-3-(1-propenyl)-
4-n-propylnaphthalene (eq 5). The precise mechanism by which
of the palladium and the bridgehead hydrogen to align in a cis
fashion and, if elimination were to occur, would produce a very
strained bridgehead olefin.
this product is formed remains uncertain, but it appears that some
kind of allene intermediate may be involved as shown in Scheme
2. This process may be related mechanistically to Trost’s
palladium-catalyzed cyclization of 1,6-enynes.5
In our preliminary studies of the scope of this nitrile annulation
chemistry, we have found that bicyclic alkenes also undergo facile
carboannulation by o-iodobenzonitrile. For example, norbornene
affords a 93% yield of the bicyclic aryl ketone, and bicyclo[2.2.2]-
oct-2-ene produces the anticipated product in 82% yield (eq 6).
This is the first example of this type of carboannulation of a
bicyclic alkene. In this case, palladium hydride elimination in
the bicyclic palladium intermediate is prevented by the inability
In conclusion, the carbon-nitrogen triple bond of simple aryl
nitriles has been observed to readily participate in organopalladium
annulation reactions. 2-Iodobenzonitrile and 2-iodophenylaceto-
nitriles react with internal alkynes and bicyclic alkenes to form
indenones, naphthenones, 2-aminonaphthalenes, and bicyclic aryl
ketones in good yields. This chemistry suggests that there may
be many other organopalladium processes which will occur
intramolecularly that normally will not occur by intermolecular
processes.
(5) (a) Smrcina, M.; Vyskocil, S.; Ma´ca, B.; Pola´sek, M.; Claxton, T. A.;
Abbott, A. P.; Kocovsky, P. J. Org. Chem. 1994, 59, 2156. (b) Smrcina, M.;
Lorenc, M.; Hanus, V.; Sedmera, P.; Kocovsky, P. J. Org. Chem. 1992, 57,
1917. (c) Smrcina, M.; Lorenc, M.; Hanus, V.; Kocovsky, P. Synlett 1991,
231. (d) Kabuto, K.; Yoshida, T.; Yamaguchi, S.; Miyano, S.; Hashimoto, H.
J. Org. Chem. 1985, 50, 3013. (e) Miyano, S.; Nawa, M.; Mori, A.; Hashimoto,
H. Bull. Chem. Soc. Jpn. 1984, 57, 2171. (f) Kawakami, Y.; Hiratake, J.;
Yamamoto, Y.; Oda, J. J. Chem. Soc., Chem. Commun. 1984, 779. (g)
Sakamoto, A.; Yamamoto, Y.; Oda, J. J. Am. Chem. Soc. 1987, 109, 7188.
(h) Lin, J.-H.; Che, C.-M.; Lai, T.-F.; Poon, C.-K.; Cui, Y. X. J. Chem. Soc.,
Chem. Commun. 1991, 468.
Acknowledgment. We thank the donors of the Petroleum Research
Fund, administered by the American Chemical Society, for partial support
of this research. Thanks are also extended to Johnson Matthey, Inc., and
Kawaken Fine Chemicals Co., Ltd., for donating the palladium acetate.
Supporting Information Available: General experimental procedures
and spectroscopic characterization of all new products (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
(6) (a) For a review, see: Trost, B. M. Acc. Chem. Res. 1990, 23, 34. (b)
Trost, B. M.; Lee, D. C. J. Am. Chem. Soc. 1988, 110, 7255. (c) Trost, B. M.;
Lee, D. C.; Rise, F. Tetrahedron Lett. 1989, 30, 651. (d) Mandai, T.; Tsuji,
J.; Tsujiguchi, Y. J. Am. Chem. Soc. 1993, 115, 5865.
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