Structure and reactivity of (η3-indolylmethyl)palladium complexes generated by the reaction of organopalladium complexes with o-alkenylphenyl isocyanide

Article abstract of DOI:10.1021/om010897o

Structure and reactivity of (η³-Indolylmethyl)palladium complexes generated by the reaction of organopalladium complexes with o-alkenylphenyl isocyanide were analyzed. The reaction of methylpalladium complexes with o-alkenylphenyl isocyanides r

Full text of DOI:10.1021/om010897o

© Copyright 2002
Volume 21, Number 4, February 18, 2002
American Chemical Society
Communications
Str u ctu r e a n d Rea ctivity of (η3-In d olylm eth yl)p a lla d iu m
Com p lexes Gen er a ted by th e Rea ction of
Or ga n op a lla d iu m Com p lexes w ith o-Alk en ylp h en yl
Isocya n id e
Kiyotaka Onitsuka, Mari Yamamoto, Shinobu Suzuki, and
Shigetoshi Takahashi*
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki,
Osaka 567-0047, J apan
Received October 15, 2001
Summary: The reaction of methylpalladium complexes
with o-alkenylphenyl isocyanides results in the successive
intramolecular insertion of the alkenyl and isocyano
groups followed by the 1,3-migration of hydrogen to give
(η3-indolylmethyl)palladium complexes (4) in good yields.
Treatment of 4 with diethylamine causes nucleophilic
attack at the exo methylene carbon to give 2-methyl-3-
(aminomethyl)indole, whereas the reactions with HCl
produce 2,3-dimethylindole derivatives.
work.3,4 Despite the high reactivity of isocyanides
toward organometallic compounds,5 there have been few
reports on approaches to indole synthesis using transi-
tion-metal mediators.6 We recently showed that the
reactions of organopalladium complexes with o-ethynyl-
phenyl isocyanide produce (E)- and (Z)-(indolidene-
methyl)palladium complexes in good yields.7 We de-
scribe here the formation of novel (η3-indolylmethyl)-
palladium complexes from the reaction with o-alkenyl-
phenyl isocyanide and their reactivity, leading to 2,3-
disubstituted indole derivatives.
Cyclization via a tandem reaction of organic molecules
mediated by transition-metal complexes is a powerful
tool for the synthesis of heterocyclic compounds. Al-
though several methods have been developed for the
construction of an indole nucleus, indole derivatives are
still fascinating targets in these synthetic reactions, due
to their importance as basic units in a wide variety of
biologically active natural products.1,2 Ortho-function-
alized aryl isocyanides have attracted much attention
as a substrate for the synthesis of the indole frame-
Treatment of complex 1a with o-vinylphenyl isocya-
nide (2a )8 at room temperature resulted in the insertion
of the isocyano group of 2a to give an iminoacyl complex
(3) (a) Fukuyama, T.; Chen, X.; Peng, G. J . Am. Chem. Soc. 1994,
116, 3127. (b) Shinada, T.; Miyachi, M.; Itagaki, Y.; Naoki, H.;
Yoshihara, K.; Nakajima, T. Tetrahedron Lett. 1996, 37, 7099. (c)
Kobayashi, Y.; Fukuyama, T. J . Heterocycl. Chem. 1998, 35, 1043. (d)
Rainier, J . D.; Kennedy, A. R. J . Org. Chem. 2000, 65, 6213.
(4) (a) Ito, Y.; Inubushi, Y.; Sugaya, T.; Kobayashi, K.; Saegusa, T.
Bull. Chem. Soc. J pn. 1978, 51, 1186. (b) Ito, Y.; Kobayashi, K.; Seko,
N.; Saegusa, T. Bull. Chem. Soc. J pn. 1984, 57, 73. (c) Orita, A.;
Fukudome, M.; Ohe, K.; Murai, S. J . Org. Chem. 1994, 59, 477.
(5) For reviews, see: (a) Yamamoto, Y.; Yamazaki, H. Coord. Chem.
Rev. 1972, 8, 225. (b) Treichel, P. M. Adv. Organomet. Chem. 1973,
11, 21. (c) Shingleton, E.; Oosthuizen, H. E. Adv. Organomet. Chem.
1983, 22, 209.
(1) For reviews, see: (a) Hegedus, L. S. Angew. Chem., Int. Ed. Engl.
1988, 27, 1113. (b) Gilchrist, T. L. J . Chem. Soc., Perkin Trans. 1 1999,
2849. (c) Gribble, G. W. J . Chem. Soc., Perkin Trans. 1 2000, 1045.
(2) For recent leading references, see: (a) Cho, C. S.; Lim, H. K.;
Shim, S. C.; Kim, T. J .; Choi, H.-J . Chem. Commun. 1998, 995. (b)
Wagaw, S.; Yang, B. H.; Buchwald, S. L. J . Am. Chem. Soc. 1998, 120,
6621. (c) Tokuyama, H.; Yamashita, T.; Reding, M. T.; Kaburagi, Y.;
Fukuyama, T. J . Am. Chem. Soc. 1999, 121, 3791. (d) Takeda, A.;
Kamijo, S.; Yamamoto, Y. J . Am. Chem. Soc. 2000, 122, 5662. (e)
Roesch, K. R.; Larock, R. C. J . Org. Chem. 2001, 66, 412.
(6) (a) J ones, W. D.; Kosar, W. P. J . Am. Chem. Soc. 1986, 108, 5640.
(b) Hsu, G. C.; Kosar, W. P.; J ones, W. D. Organometallics 1994, 13,
385.
10.1021/om010897o CCC: $22.00 © 2002 American Chemical Society
Publication on Web 01/17/2002

582 Organometallics, Vol. 21, No. 4, 2002
Communications
Sch em e 1
F igu r e 1. ORTEP drawing of 3a . Hydrogen atoms are
omitted for clarity. Bond distances and angles are included
in the Supporting Information.
(3a ) in 86% yield (Scheme 1). Similar reaction with
o-((methoxycarbonyl)ethenyl)phenyl isocyanide (2b)3a,c
also produced an insertion product (3b) in 97% yield.
These complexes were fully characterized by spectral
analyses as well as by X-ray crystallography, as shown
in Figure 1.9
No intramolecular insertion of the vinyl group took
place upon heating a chloroform solution of 3a at 45 °C,
in contrast to the results with the acetylenic analogue.7
Elevation of the reaction temperature caused decompo-
sition of 3a to Pd(PEt3)2Cl2 and unidentified organic
compounds. However, treatment of 3a with AgPF6 at 0
°C quantitatively gave a new palladium complex (4a ),
which was isolated in 50% yield. The 31P NMR spectrum
of 4a showed two doublet signals at δ 7.1 and 29.8 with
the coupling constant J PP ) 29 Hz, which is character-
istic of a cis-bis(phosphine)palladium complex, along
with a septet signal at δ -143.3 (J PF ) 713 Hz) due to
F igu r e 2. ORTEP drawing of 4a . Hydrogen atoms and a
counteranion are omitted for clarity. Selected bond dis-
tances (Å) and angles (deg) are as follows: Pd(1)-P(1) )
2.239(2), Pd(1)-P(2) ) 2.277(3), Pd(1)-C(1) ) 2.105(9),
Pd(1)-C(2) ) 2.189(9), Pd(1)-C(3) ) 2.620(9), C(1)-C(2)
) 1.42(1), C(2)-C(3) ) 1.42(1); P(1)-Pd(1)-P(2) ) 104.97(9),
C(1)-C(2)-C(3) ) 126(1).
1
the counteranion PF6-. In the H NMR spectrum, the
signals due to the vinyl protons disappeared, and two
new signals assignable to those on the part derived from
the vinyl group in the range of δ 2-4 along with a broad
signal at δ 10.36 were observed. The IR spectrum
revealed an absorption at 3304 cm-1. These data are
consistent with the formation of an indole skeleton
produced by insertion of the vinyl group into the Pd-C
bond followed by a hydrogen shift to the nitrogen atom.
The structure of 4a was unequivocally determined by
an X-ray diffraction study, as shown in Figure 2, to be
an η3-indolylmethyl complex.10 The most striking struc-
tural feature is that the Pd(1)-C(3) bond is much longer
than Pd(1)-C(1) and Pd(1)-C(2). Although a similar
phenomenon has often been observed in η3-benzyl
complexes,11 the length of the Pd(1)-C(3) bond is
remarkable. This may be due to the contribution of an
Ch a r t 1
η2 structure (5a ) (Chart 1), in which the formal oxidation
state of the palladium atom is zero and the positive
charge is located on the nitrogen atom.12 The high
stability of the indole skeleton in 4a would be a driving
force for the 1,3-hydrogen shift in the intermediate (6a ),
which was produced by intramolecular olefin insertion
(7) Onitsuka, K.; Segawa, M.; Takahashi, S. Organometallics 1998,
17, 4335.
(8) Brown, R. F. C.; Hooley, N.; Irvine, F. N. Aust. J . Chem. 1974,
27, 671.
(9) Crystallographic data for 3a : formula C22H40ClNP2Pd, fw )
522.37, monoclinic, space group P21/n (No. 14), a ) 10.8148(9) Å, b )
14.311(1) Å, c ) 16.6209(8) Å, â ) 98.873(5)°, V ) 2541.7(2) Å3, Z ) 4,
dcalcd ) 1.365 g cm-3, -70 °C, ω-2θ scan, 6° < 2θ < 55°, µ(Mo KR) )
9.69 cm-1, R (Rw) ) 0.027 (0.044) for 244 parameters against 5167
reflections with I > 3.0σ(I) out of 5833 unique reflections (Rint ) 0.020)
by full-matrix least-squares methods, GOF ) 1.24.
(10) Crystallographic data for 4a : formula C22H40F6NP3Pd, fw )
631.88, monoclinic, space group P21/c (No. 14), a ) 14.328(4) Å, b )
11.429(4) Å, c ) 17.842(3) Å, â ) 97.97(2)°, V ) 2893(1) Å3, Z ) 4,
dcalcd ) 1.450 g cm-3, 23 °C, ω-2θ scan, 6° < 2θ < 55°, µ(Mo KR) )
8.57 cm-1, R (Rw) ) 0.059 (0.081) for 298 parameters against 2982
reflections with I > 3.0σ(I) out of 6649 unique reflections (Rint ) 0.048)
by full-matrix least-squares methods, GOF ) 1.09.

Communications
Organometallics, Vol. 21, No. 4, 2002 583
Sch em e 2
F igu r e 3. ORTEP drawing of syn-4d . Hydrogen atoms,
solvent molecules, and a counteranion are omitted for
clarity. Selected bond distances (Å) and angles (deg) are
as follows: Pd(1)-P(1) ) 2.278(2), Pd(1)-P(2) ) 2.301(1),
Pd(1)-C(1) ) 2.118(4), Pd(1)-C(2) ) 2.184(4), Pd(1)-C(3)
) 2.713(4), C(1)-C(2) ) 1.436(6), C(2)-C(3) ) 1.408(6);
P(1)-Pd(1)-P(2) ) 94.41(4), C(1)-C(2)-C(3) ) 120.9(4).
Sch em e 3
from 3a . The η3 coordination mode in 4a is stable
compared to that in analogous (η3-benzyl)palladium
complexes. Thus, treatment of Et4NCl did not change
the coordination mode to η1, whereas (η3-benzyl)palla-
dium complexes are easily converted into η1-benzyl
complexes under similar conditions.13 Reaction of 3b
with AgPF6 also gave an η3-indolylmethyl complex (4b),
which consisted of two isomers, syn- and anti-4b, in a
ratio of 71:29 as determined by 1H and 31P NMR spectra.
Upon treatment of complex 1b, which has the ligand
bis(diphenylphosphino)ethane (dppe), with 2a at room
temperature, both the isocyano and olefinic groups of
2a smoothly inserted into the Pd-C bond in the absence
of AgPF6 to give an η3-indolylmethyl complex (4c) in
76% isolated yield (Scheme 2). Reaction of complex 1c,
which has the ligand bis(diphenylphosphino)propane
(dppp), also produced complex 4d , which was isolated
in 46% yield. Although a mixture of syn- and anti-4e
was produced in a ratio of 78:22 from the reaction of
complex 1c with 2b, the major product was isolated by
recrystallization from a CHCl3-CH2Cl2-hexane solu-
tion and was confirmed to be syn-4e by an X-ray
analysis (Figure 3).14 The Pd(1)-C(3) bond is slightly
longer than the corresponding bond in 4a , suggesting
that the η2-coordinated structure has a greater contri-
bution, since the electron-withdrawing nature of the
methoxycarbonyl group stabilizes the low oxidation
state of the palladium species. The reaction of complex
1d , which has 2,2′-bipyridine as a bidentate ligand, with
2a smoothly proceeded to give complex 4f in 77% yield.
The (η3-indolylmethyl)palladium complex 4 shows
reactivities similar to those of common (η3-allyl)palla-
dium complexes. Complexes 4d and 4e underwent the
quantitative cleavage of the Pd-C bond in an η3 fashion
by treatment with HCl to give 2,3-dimethylindole
derivatives (7) in quantitative yields15 (Scheme 3). On
the other hand, the η3-indolylmethyl group also under-
went nucleophilic attack.16 Treatment of complex 4d
with dialkylamine at room temperature selectively
produced 2-methyl-3-(aminomethyl)indole derivatives
(8) in good yields.
(11) (a) Bleeke, J . R.; Burch, R. R.; Coulman, C. L.; Schardt, B. C.
Inorg. Chem. 1981, 20, 1316. (b) Crascall, L. E.; Litster, S. A.;
Redhouse, A. D.; Spencer, J . L. J . Organomet. Chem. 1990, 394, C35.
(c) Gatti, G.; Lo´pez, J . A.; Mealli, C.; Musco, A. J . Organomet. Chem.
1994, 483, 77. (d) Werner, H.; Scha¨fer, M.; Nu¨rnberg, O.; Wolf, J . Chem.
Ber. 1994, 127, 27. (e) Djukic, J .-P.; Do¨tz, K. H.; Pfeffer, M.; De Cian,
A.; Fischer, J . Organometallics 1997, 16, 5171. (f) Wang, T.-F.; Hwu,
C.-C.; Tsai, C.-W.; Wen, Y.-S. J . Chem. Soc., Dalton Trans. 1998, 2091.
(12) Ogoshi, S.; Yoshida, T.; Nishida, T.; Morita, M.; Kurosawa, H.
J . Am. Chem. Soc. 2001, 123, 1944.
In summary, we have demonstrated the stoichiomet-
ric transformation of o-alkenylphenyl isocyanides into
2,3-disubstituted indole derivatives on a palladium atom
through η3-indolylmethyl intermediates. Further studies
focused on the application of the present finding to a
catalytic system are now in progress.
(13) (a) Becker, Y. Stille, J . K. J . Am. Chem. Soc. 1978, 100, 845.
(b) Lin, Y.-S.; Yamamoto, A. Bull. Chem. Soc. J pn. 1998, 71, 723.
(14) Crystallographic data for 4e‚CHCl3‚2H2O: formula C40H43Cl4-
NO4P2Pd, fw ) 911.94, monoclinic, space group P21/c (No. 14),
a ) 15.446(3) Å, b ) 21.114(2) Å, c ) 13.115(4) Å, â ) 106.37(1)°,
V ) 4105(1) Å3, Z ) 4, dcalcd ) 1.475 g cm-3, -50 °C, ω-2θ scan,
6° < 2θ < 55°, µ(Mo KR) ) 8.31 cm-1, R (Rw) ) 0.055 (0.092) for
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Science, Sports and Culture. We thank
The Material Analysis Center, ISIR, Osaka University,
for supporting our study with spectral measurements,
X-ray crystallography, and microanalyses.
469 parameters against 6823 reflections with
I > 3.0σ(I) out of
9410 unique reflections (Rint ) 0.043) by full-matrix least-squares
methods, GOF ) 1.22.
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental details and full characterization data for all new
complexes and X-ray crystallographic data for complexes 3a ,
4a , and 4e. This material is available free of charge via the
Internet at http://pubs.acs.org.
(15) A similar reaction of [(η3-allyl)Pd(dppp)]Cl with HCl resulted
in quantitative elimination of the allyl group to give Pd(dppp)Cl2. Rapid
Pd-allyl bond cleavage has been observed in the reaction of (η1-allyl)-
palladium complexes with an equimolar amount of electrophiles:
Kurosawa, H.; Urabe, A.; Miki, K. Kasai, N. Organometallics 1986, 5,
2002.
(16) Roberts, J . S.; Klabunde, K. J . J . Am. Chem. Soc. 1977, 99, 2509.
OM010897O