Can agostic interaction affect regiochemistry of carbopalladation? Reverse regioselectivity in the palladium-catalyzed dimerization of aryl acetylenes [22]

Full text of DOI:10.1021/ja016934k

J. Am. Chem. Soc. 2001, 123, 11107-11108
11107
Table 1. Palladium-Catalyzed Head-to-Head Dimerization of
Can Agostic Interaction Affect Regiochemistry of
Carbopalladation? Reverse Regioselectivity in the
Palladium-Catalyzed Dimerization of Aryl Acetylenes
Terminal Aryl Acetylenesa
R
time, h
yield of 2, %b
1
2
3
4
5
6
7
8
9
Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
2
4
3
1.5
2
16
1.5
24c
20
70
86
57
91
93
80
79
13d
4-MeC6H4
4-MeOC6H4
4-NCC6H4
4-F3CC6H4
1-naphthyl
2-naphthyl
9-anthryl
n-nonyl
Marina Rubina and Vladimir Gevorgyan*
Department of Chemistry
UniVersity of Illinois at Chicago
845 West Taylor Street, Chicago, Illinois 60607-7061
3e,f
ReceiVed August 24, 2001
ReVised Manuscript ReceiVed September 28, 2001
a [(π-allyl)PdCl]2 5 mol %, TDMPP 10 mol %, Et2NH 1 equiv, rt,
THF (1 M). b Isolated yield unless specified otherwise. c Reaction was
carried out at 60 °C. d 13% of head-to-tail product was also formed.
e NMR yield. f 20% of head-to-tail product was also formed, 30% of
starting material left.
Dimerization of terminal alkynes is a very practical and
straightforward approach to conjugated enynes - important
building blocks for synthetic organic chemistry and key units
found in a variety of biologically active compounds.1,2 A number
of transition metal complexes effectively catalyze alkyne dimer-
ization;3 however, in most cases a mixture of regio- and stereo-
isomeric enynes 2-4 is obtained (eq 1). The factors that affect
Further optimization indicated that [(π-allyl)PdCl]2 efficiently
catalyzed formation of the head-to-head dimers.9 It was also found
that only electron-rich, bulky, hemi-labile ligands such as
TDMPP10 gave exclusively the head-to-head product 2a, whereas
use of other phosphines resulted in a dramatic drop of both product
regioselectivity and yield.11 Assuming excess TDMPP was
necessary for maintaining high basicity of the reaction media, a
number of amines as additives were tested. Indeed, the addition
of 1 equiv of Et2NH to the [(π-allyl)PdCl]2/TDMPP mixture
allowed for the reduction of the phosphine ligand amount down
to 8-10 mol % (to maintain the Pd:P ratio of 1:1), and shortened
the reaction time to 2 h. Finally, these optimized conditions were
tested for the dimerization reaction of different terminal alkynes
(Table 1).
It was found that most arylacetylenes tested smoothly under-
went the dimerization reaction to produce the head-to-head dimers
in good to very high yield (Table 1, entries 1-7). It is worth
noting that in all the above cases no other regio- or stereoisomeric
products were detected by GC/MS and NMR analyses of the crude
reaction mixtures. 9-Anthryl alkyne 1h reacted much more
sluggishly and unselectively (entry 8). Finally, aliphatic alkyne
1i did not produce the corresponding head-to-head dimer 2i at
all (entry 9).12 Analysis of the results summarized in the Table 1
revealed that both good yields and high selectivity were observed
only for the dimerization of aryl alkynes possessing ortho
hydrogen atoms.13 To test this proposal, a series of differently
ortho-substituted aryl alkynes 1j-n have been synthesized and
examined in the dimerization reaction (eq 2, Table 2). We found
regio- and stereoselectivity depend mainly on the electronic effects
and steric hindrance at the alkyne substituent and the coordination
sphere of the metal. Although a powerful method for selective
construction of head-to-tail enynes 3 in the presence of the Pd-
(OAc)2-TDMPP (TDMPP ) P[(2,6-OMe)2C6H3]3) system has
been developed by Trost,4 precedents on Pd-catalyzed head-to-
head dimerization of terminal alkynes are limited to the terminal
silyl acetylenes4,5 and nonselective dimerization of phenylacet-
ylene.6 Herein we wish to report an unusual, highly regio- and
stereoselective head-to-head dimerization of terminal aryl acet-
ylenes 1 (R ) Ar) in the presence of a palladium catalyst to give
E-enynes 2.
In the course of our investigation of sequential trimerization
reaction7 we found that the Pd(PPh3)4 and Pd2dba3‚CHCl3/(o-
Tol)3P (dba ) dibenzylideneacetone) systems efficiently catalyze
head-to-tail dimerization of terminal acetylenes to produce enynes
3. Surprisingly, we discovered that the Pd2dba3‚CHCl3/TDMPP
combination not only produced the head-to-tail enyne 3a (R )
Ph), but also an unexpected regioisomeric head-to-head enyne
2a. The best head-to-head selectivity was achieved with 1:5 Pd/P
ratio.8 However, other alkynes tested reacted in a less selective
fashion.
(8) It was a rather surprising finding, since it was demonstrated on the
Pd(II)-TDMPP series (Kurosawa, H.; Tsuboi, A.; Kawasaki, Y.; Wada, M.
Bull. Chem. Soc. Jpn. 1987, 60, 3563) and supported by our experiments on
Pd2dba3‚CHCl3/TDMPP system, that one Pd atom can accommodate no more
than one TDMPP ligand at a time. See Supporting Information for details.
(9) [(π-allyl)PdCl]2/TDMPP combination used in a ratio of 1:5 (Pd:P) gave
head-to-head dimer 2a exclusively in 93% NMR yield after stirring overnight
at room temperature.
(10) It is well-documented that TDMPP can serve as bidentate ligand with
hemilabile metal-O bond. See: Ma, J.-F.; Kojima, Y.; Yamamoto, Y. J.
Organomet. Chem. 2000, 616, 149.
(11) Employment of monodentate PCy3, which is almost as basic as
TDMPP, resulted in no reaction. On the other hand, use of the more basic,
hemilabile P[(2,4,6-OMe)3C6H2]3 gave the same result as the reaction with
TDMPP. For the discussion on basicity of the phosphines, see: Wang, D.;
Angelici, R. Inorg. Chem. 1996, 35, 1321.
(12) Analogously, attempts to dimerize non-aryl alkynes with functionalized
side chain under above-mentioned conditions resulted in total decomposition
of the reaction mixtures.
(13) It occurred to us that possible interaction between the metal center
and the ortho H of the aryl ring at some stage of the reaction may be
responsible for the observed reversal of the regiochemistry of dimerization.
For stabilization of transition metal complexes caused by agostic coordination
of o-C-H bond to a metal center see, for example: Crabtree, R. H. Angew.
Chem., Int. Ed. Engl. 1993, 32, 789.
(1) See, for example: (a) Trost, B. M. Science 1991, 254, 1471. (b)
Nicolaou, K. C.; Dai, W. M.; Tsay, S. C.; Estevez, V. A.; Wrasidlo, W. Science
1992, 256, 1172.
(2) Hubner, H.; Haubmann, C.; Utz, W.; Gmeiner, P. J. Med. Chem. 2000,
43, 756.
(3) For most recent reviews on Ru-catalyzed dimerization, see: (a) Trost,
B. M.; Toste, D.; Pinkerton, A. Chem. ReV. 2001, 101, 2067. (b) Bruneau,
C.; Dixneuf, P. H. Acc. Chem. Res. 1999, 32, 311. On other transition metals,
see: (c) (M ) Y) Duchateau, R.; van Wee, C. T.; Teuben, J. H. Organome-
tallics 1996, 15, 2291. (d) (M ) Co, Rh) Field, L. D.; Ward, A. J.; Turner,
P. Aust. J. Chem. 1999, 52, 1085. (e) (M ) Ir) Ohmura, T.; Yorozuya, S.;
Yamamoto, Y.; Miyaura, N. Organometallics 2000, 19, 365. (f) (M ) Ti)
Akita, M.; Yasuda, H.; Nakamura, A. Bull. Chem. Soc. Jpn. 1984, 57, 480.
(4) Trost, B. M.; Sorum, M. T.; Chan, C.; Harms, A. E.; Ruhter, G. J. Am.
Chem. Soc. 1997, 119, 698.
(5) Ishikawa, M.; Ohshita, J.; Ito, Y.; Minato, A. J. Organomet. Chem.
1988, 346, C58.
(6) Herrmann, W.; Bohm, V.; Gstottmayr, C.; Grosche, M.; Reisinger, C.-
P.; Weskamp, T. J. Organomet. Chem. 2001, 617-618, 616.
(7) Gevorgyan, V.; Radhakrishnan, U.; Takeda, A.; Rubina, M.; Rubin,
M.; Yamamoto, Y. J. Org. Chem. 2001, 66, 2835.
10.1021/ja016934k CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/16/2001

11108 J. Am. Chem. Soc., Vol. 123, No. 44, 2001
Communications to the Editor
Table 2. Palladium-Catalyzed Dimerization of Differently
Ortho-Substituted Phenylacetylenes
Scheme 1
R1
R2
time, h
yield of 2, %a
1
2
3
4
5
6
H
H
H
Me
H
F
1a
1j
1k
1l
1m
1n
2
48
36
2
24
24
70b
Me
Me
F
F
OMe
50c,d
NRe
71
NRe
NRe
OMe
a Isolated yield. b Result from the Table 1. c NMR yield. d 17% of
head-to-tail product was also formed. e Formation of traces of isomeric
dimerization products were observed by GC/MS analyses.
that the introduction of one methyl group (1j) substantially
diminished the efficiency of the head-to-head dimerization
reaction (entry 2), whereas substitution of both ortho hydrogen
atoms with a methyl group completely inhibited this process (entry
3). In contrast to its methyl analogue, R-fluorophenylacetylene
1l easily underwent the dimerization affording the enyne 2l (entry
4) with an efficiency similar to that observed for phenyl-acetylene
(entry 1). As expected, R,R′-difluoroarylalkyne 1m did not
undergo dimerization at all (entry 5).14 Dimethoxy derivative 1n
did not undergo dimerization reaction either (entry 6). It became
obvious that indeed, at least one ortho hydrogen in the molecule
of aryl acetylene is needed for a selective head-to-head dimer-
ization reaction.
Taking into account the experimental evidence discussed above,
we suggest the following rationale for the mechanism of this
unusual transformation (Scheme 1). Initially, Pd(II) species 6 is
transformed into the catalytically active complex A. This step is
accomplished by reduction of 6 with diethylamine producing
allylamine 7 as a byproduct.15 Palladium(0) species A is stabilized
by TDMPP as an electron-rich chelating ligand and aryl acetylene
as a π-acceptor.16 Subsequent reversible17 oxidative addition of
the aryl acetylene provides a σ-complex B. Coordination of
another molecule of 1 with B produces complexes C and C′ in
which η2-coordinated alkyne is differently oriented toward the
σ-alkynyl palladium moiety. For the following carbopalladation
step, potentially, there are two regiochemistry-determining path-
ways, I and II. Dimerization of alkynes 1h and 1i (Table 1, entries
8, 9) partly proceeds via path I, a Markovnikov-type addition,
which is controlled by electronic factors and results in the
formation of the vinylpalladium species F leading to the head-
to-tail dimer 3.4,7 On the other hand, aryl alkynes possessing ortho
hydrogen atoms undergo carbopalladation via path II, producing
the σ-complex E which affords the head-to-head product 2. We
propose that transition state D is responsible for path II. Although
such a transition state should be electronically less favorable, the
contribution of an agostic interaction of the metal center with
the o-C-H bonds would decrease the energy barrier for the
reaction making this pathway possible for aromatic substrates
possessing ortho hydrogen atoms.18 Kinetic isotope effect studies
that may provide additional support for the involvement of agostic
interaction in the stabilization of the transition state were
performed.19 The substantial value of the isotope effect obtained,
kH/kD ) 3.0 ( 0.1, supports the above proposal.20 The observed
median kH/kD value indicates that the reaction may or may not
proceed through the reversible insertion of the metal into the
o-C-H bond of aryl alkyne.21 However, our test experiments with
phenyl-d5-acetylene and 1a demonstrated that H/D exchange at
the ortho position of aryl acetylenes does not occur during the
reaction, which would be unavoidable in the case if the reversible
insertion of metal into the o-C-H(D) bond takes place. Although
at this stage it is not entirely clear why the 1:1 Pd-TDMPP
complex should be particularly effective for the agostic interaction
with the o-C-H bond, we believe that the proposed mechanistic
rationale reasonably explains the unusual head-to-head regio-
chemistry observed in the dimerization of aryl alkynes.
In conclusion, a novel, highly regio- and stereoselective head-
to-head dimerization of aryl alkynes catalyzed by Pd(0) complexes
was found. It was proposed that an agostic interaction between
the transition metal and ortho protons of the aromatic ring in the
substrate is responsible for the observed unusual anti-Markovnikov
regioselectivity of the reaction. To the best of our knowledge,
there are no precedents on agostic interactions in the transition
state that affect the regiochemistry of the carbopalladation process.
Acknowledgment. The support of the National Science Foundation
(CHE-0096889) is gratefully acknowledged.
Supporting Information Available: Experimental details (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
JA016934K
(14) A control experiment with 1m under the head-to-tail dimerization
conditions described in the ref 4 proceeded smoothly affording a head-to-tail
dimer 3m in good yield.
(18) Heteroatoms at the ortho position could have also stabilized a complex
of type D via donation of a lone pair of electrons to the palladium center.
However, as it is obvious from the Table 2 (entry 6), it is not the case.
(19) Deuterium kinetic isotope effect was calculated as a ratio of kH/kD,
where kH and kD are observed rate constants measured for the reactions of
phenylacetylene and phenyl-d5-acetylene, respectively (See Supporting In-
formation for details).
(20) For the precedents of a substantial deuterium kinetic isotope effect
caused by agostic interaction (kH/kD ) 2.30-2.55) in the Zr-catalyzed R-olefin
polymerization, see: Krauledat, H.; Brintzinger, H.-H. Angew. Chem., Int.
Ed. Engl. 1990, 29, 1412.
(21) Yagyu, T.; Aizawa, S.; Funahashi, S. Bull. Chem. Soc. Jpn. 1998, 71,
619.
(15) Formation of allyldiethylamine was detected by GC/MS and NMR
analyses of reaction mixtures. For detailed mechanism of this known
transformation, see: (a) Bricout, H.; Carpentier, J.-F.; Montreux, A. Tetra-
hedron 1998, 54, 1073. (b) Canovese, L.; Visentin, F.; Uguagliati, P.; Chessa,
G.; Lucchini, V.; Bandoli, G. Inorg. Chim. Acta 1998, 275-276, 385.
(16) (a) For examples of analogous stabilization of Pd-TDMPP complex
with alkenes, see 15b. (b) The formation of some 1:1:1 Pd-TDMPP-arylalkyne
complex was observed by low-temperature NMR experiments. See Supporting
Information for details.
(17) Reversibility of the transformation A to B was supported by observed
rapid H/D scrambling between series of protio- and deuterio-phenylacetylenes
and diethylamine. See Supporting Information for details.