Benzannulation from alkynes and allyl tosylates via a π-allylpalladium intermediate

Article abstract of DOI:10.1021/ol991406n

(Graph presented) Allyl tosylate is a good allyl source for a novel palladium-catalyzed benzannulation that affords polysubstituted benzenes from 1 mol of an allyl compound and 2 mol of internal alkynes. Using triphenyl phosphite as a ligand, the reaction with terminal alkynes gave trisubstituted benzenes regioselectively.

Full text of DOI:10.1021/ol991406n

ORGANIC
LETTERS
2000
Vol. 2, No. 5
655-657
Benzannulation from Alkynes and Allyl
Tosylates via a π-Allylpalladium
Intermediate
Naofumi Tsukada,* Shuichi Sugawara, and Yoshio Inoue
Department of Materials Chemistry, Graduate School of Engineering,
Tohoku UniVersity, Sendai 980-8579, Japan
tsukada@aporg.che.tohoku.ac.jp
Received December 28, 1999
ABSTRACT
Allyl tosylate is a good allyl source for a novel palladium-catalyzed benzannulation that affords polysubstituted benzenes from 1 mol of an
allyl compound and 2 mol of internal alkynes. Using triphenyl phosphite as a ligand, the reaction with terminal alkynes gave trisubstituted
benzenes regioselectively.
Remarkable progress has been made in the application of
π-allylpalladium chemistry to catalytic organic synthesis. A
π-allylpalladium intermediate reacts with varied reactants
including soft and hard nucleophiles, aldehydes, carbon
monoxide, and organometallics to give various allylated
organic compounds normally.1 However, insertion of an
alkyne, which is one of the simplest organic molecules, to a
π-allylpalladium species has not been reported except for a
dimerization-allylation reaction of terminal alkynes2 and
several intramolecular reactions followed by carbonylation.3
On the other hand, typical allyl metals are known to undergo
allylmetalation to alkynes to give 1,4-pentadienyl com-
pounds.4,5 Furthermore, allyl transition metal complexes show
a wider range of reactivities toward alkynes.6 For example,
five-membered6b,c or six- and seven-membered6d-f ring
systems are obtained by incorporation of 1 or 2 mol of
alkynes, respectively. However, a stoichiometric amount of
allylmetals is needed in these reactions, except for the
reaction of π-allylnickel, which is an intermediate on the
allylation of alkynes catalyzed by Ni(0).7,8 Herein we wish
to report a palladium-catalyzed synthesis of pentasubstituted
benzenes from 1 mol of allyl tosylates and 2 mol of alkynes
(4) Reviews: (a) Normant, J. F.; Alexakis, A. Synthesis 1981, 841. (b)
Negishi, E. Pure Appl. Chem. 1981, 53, 2333. (c) Oppolzer, W. Angew.
Chem., Int. Ed. Engl. 1989, 28, 38. (d) Knochel, P. In ComprehensiVe
Organometallic Chemistry II; Able, E. W., Stone, F. G. A., Wilkinson G.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 4, p 865. (e) Yamamoto, Y.;
Asao, N. Chem. ReV. 1993, 93, 2207.
(5) Transition metal or Lewis acid catalysts accelerate the reaction;,
see: (a) Miller, J. A.; Negishi, E. Tetrahedron Lett. 1984, 25, 5863. (b)
Asao, N.; Matsukawa, Y.; Yamamoto, Y. Chem. Commun. 1996, 1513. (c)
Asao, N.; Yoshikawa, E.; Yamamoto, Y. J. Org. Chem. 1996, 61, 1. 4874.
(d) Yoshikawa, E.; Gevorgyan, V.; Asao, N.; Yamamoto, Y. J. Am. Chem.
Soc. 1997, 119, 6781. See also ref 4b.
(6) (a) Betz, P.; Jolly, P. W.; Kruger, C.; Zakrzeuski, U. Organometallics
1991, 10, 3520. (b) Lutsenko, Z. L.; Aleksandrov, G. G.; Petrovskii, P. V.;
Shubina, E. S.; Andrianov, V. G.; Struchkov, Y. Y.; Ruvezhov, A. Z. J.
Organomet. Chem. 1985, 281, 349. (c) Nehl, H. Chem. Ber. 1993, 126,
1519. (d) Lutsenko, Z. L.; Petrovskii, P. V.; Bezrukova, A. A.; Ruvezhov,
A. Z. Bull. Acad. Sci. USSR. DiV. Chem. Sci. 1988, 37, 735. (e) Schwiebert,
K. E.; Stryker, J. M. J. Am. Chem. Soc. 1995, 117, 8275. (f) Etkin, N.;
Dzwiniel, T. L.; Schweibert, K. E.; Stryker, J. M. J. Am. Chem. Soc. 1998,
120, 9702. (g) Tang, J.; Shinokubo, H.; Oshima, K. Organometallics 1998,
17, 290. See also the citations contained within ref 6a-g.
(1) Reviews: (a) Godleski, S. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, p
585. (b) Tsuji, J.; In Palladium Reagents and Catalysts, InnoVations in
Organic Synthesis; Wiley: London, 1995; p 290. For reaction with
aldehydes, see also: (c) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am.
Chem. Soc. 1996, 118, 6641. (d) Nakamura, H,; Shim, J.-G.; Yamamoto,
Y. J. Am. Chem. Soc. 1997, 119, 8113.
(2) Inoue, Y.; Ohuchi, K.; Kawamata, T.; Ishiyama, J.; Imaizumi, S.
Chem. Lett. 1991, 835.
(3) (a) Oppolzer, W.; Keller, T. H.; Zurita, M. B.; Stone, C. Tetrahedron
Lett 1989, 30, 5883. (b) Oppolzer, W.; Xu, J. Z.; Stone, C. HelV. Chim.
Acta 1991, 74, 465. (c) Keese, R.; Guidetti-Grept, R.; Herzog, B.
Tetrahedron Lett. 1992, 33, 1207. (d) Ihle, N. C.; Heathcock, C. H. J. Org.
Chem. 1993, 58, 560. (e) Oppolzer, W.; Robyr, C. Tetrahedron 1994, 50,
415.
10.1021/ol991406n CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/12/2000

that proceeds via insertion of alkyne to a π-allylpalladium
intermediate.
Table 1. Palladium-Catalyzed Benzannulationa
During the investigation into the reactivity of cationic
π-allylpalladium complexes toward organic compounds, we
found that the acetonitrile-coordinated complex 1 reacted
with excess 4-octyne 2a at 80 °C in the presence of 1 equiv
of triphenylphosphine per palladium to afford 1-methyl-
2,3,4,5-tetrapropylbenzene 3a in 52% yield (eq 1).9 In
contrast, without addition of triphenylphosphine, only a trace
amount of 3a was obtained, and the reaction using 2 equiv
of triphenylphosphine or 1 equiv of bidentate phosphine
ligand like dppe did not yield 3a at all. (π-Allyl)chloro-
(triphenylphosphine)palladium 4 also gave no products under
the same conditions. These results imply that the present
benzannulation need the presence of 1 equiv of triphen-
ylphosphine and at least one weakly coodinating ligand on
palladium.10 More than two phosphorus atoms per palladium
or a firmly coodinating choride ligand would disturb the
benzannulation. On the basis of these findings in the
stoichiometric reactions, the catalytic benzannulation reaction
was then explored.
entry
alkyne
R
product
yieldb/%
1
2
3
4
5
6
2b
2c
2d
2e
2f
Me
Et
3b
3c
3d
3e
3f
41 (63)
93
82
(28)
32
41
n-Bu
Ph
CH2OMe
CO2Me
2g
3g
a Reaction conditions: allyl tosylate (0.5 mmol), 2 (2.0 mmol),
Pd2(dba)‚CHCl3 (0.025 mmol), PPh3 (0.05 mmol), 1,2-dichloroethane (3
mL) at 80 °C for 12 h. Isolated yields (NMR yield in parentheses).
b
Diphenylacetylene 2e also afforded the sterically crowded
product 3e in 28% yield (entry 4). In this reaction, allyl
tosylate was completely consumed, while unreacted 2e was
recovered. Ether group-containing alkyne 2f reacted with
allyl tosylate to give 3f in low yield (entry 5). Alkyne 2g
bearing electron-withdrawing groups exhibited decreased
reactivity to give the benzene derivative 3g in 41% yield
(entry 6).11
The reactions of several allyl tosylates were also inves-
tigated. Crotyl and (E)-2-hexenyl tosylates (5a and 5b) took
part in the reaction to produce the corresponding pentasub-
stituted benzenes 6a and 6b in 61% and 30% yield,
respectively, upon reaction with 2a (eq 4). Besides internal
alkynes, terminal alkynes 2h and 2i reacted as well (eq 5).
Although when [Pd2(dba)3]‚CHCl3-PPh3 was used as cata-
lyst the regioselectivity was not amenable to affording a
mixture of isomers of di-tert-butyl(or diphenyl)methylben-
zene, [Pd2(dba)3]‚CHCl3-P(OPh)3 showed high regioselec-
[Pd2(dba)3]‚CHCl3 combined with 1 equiv of triphen-
ylphosphine to palladium was used as a catalyst since
oxidative addition of an allyl ester or halide to Pd(0) can
generate a π-allylpalladium complex in situ. At first, the
reaction of 2a with a typical allylating agent, allyl bromide
or allyl acetate, was examined (eq 2). However, 3a was not
afforded at all. This result may be ascribed to the formation
of an inactive π-allyl complex bearing bromide or acetate
ligand, which coordinates to the palladium center firmly.
Therefore, we intended to incorporate a weakly ligating
anion. The reaction with allyl trifluoroacetate gave 3a,
although the yield was low. Allyl mesylate was more
reactive, giving 3a in 80% yield. Finally, we discovered that
allyl tosylate was a good allyl source for this benzannulation
to afford 3a in 91% yield.
(7) Reviews: (a) Billington, D. C. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, p
423. (b) Chiusoli, G. P. Acc. Chem. Res. 1973, 6, 422. (c) Casser, L.;
Chiusoli, G. P.; Guerrieri, F. Synthesis 1973, 509. (d) Llebaria, A.; Moreto´,
J. M. J. Organomet. Chem. 1993, 451, 1.
(8) (a) Ikeda, S.; Cui, D.-M.; Sato, Y. J. Org. Chem. 1994, 59, 6877. (b)
Cui, D.-M.; Tsuzuki, T.; Miyake, K.; Ikeda, S.; Sato, Y. Tetrahedron 1998,
54, 1063. (c) Ikede, S.; Miyashita, H.; Sato, Y. Organometallics 1998, 17,
4316.
(9) Without addition of PPh3, only a trace amount of 3a was obtained.
(10) (a) Kawataka, F.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn.
1995, 68, 654. (b) Kayaki, Y.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc.
Jpn. 1997, 70, 917.
(11) A conjugate addition product of p-toluenesulfonic acid to 2g was
obtained as a byproduct, whereas unreacted 2g was also recovered.
(12) See the Supporting Information.
(13) It is not clear at the present time how the insertion of alkynes to
the palladium-allyl bond occur. However, it is known that insertion reaction
of an intramolecular alkene to a π-allylpalladium proceeds via a cationic
π-allyl complex coordinated with the alkene: Go´mez-Bengoa, E.; Cuerva,
J. M.; Echavarren, A. M.; Matrorell, G. Angew. Chem., Int. Ed. Engl. 1997,
36, 767. See also; Meching, S.; Keim, W. Organometallics 1996, 15, 2650.
(14) Zhang, Y.; Negishi, E. J. Am. Chem. Soc. 1989, 111, 3454.
(15) Reductive elimination of HX from HPdX and protonation of Pd(0)
with HX may be reversible, see: Grushin, V. V. Chem. ReV. 1996, 96,
2011.
(16) (a) Suzuki, H.; Itoh, K.; Ishii, Y.; Simon, K.; Ibers, J. A. J. Am.
Chem. Soc. 1976, 98, 8494. (b) Brown, L. D.; Itoh, K.; Suzuki, H.; Hirai,
K.; Ibers, J. A. J. Am. Chem. Soc. 1978, 100, 8232. (c) Munz, C.; Stephan,
C.; tom Dieck, M. J. Organomet. Chem. 1991, 407, 413.
Table 1 summarizes the results of the benzannulation using
allyl tosylate and various internal symmetric alkynes. In all
cases, the cyclotrimerization of excess alkynes to hexasub-
stituted benzenes was sufficiently suppressed (yield <6%),
although some polymerization of the alkynes took place.
Dialkylethynes 2b-d provided the corresponding pentasub-
stituted benzenes 3b-d in good to high yields (entries 1-3).
656
Org. Lett., Vol. 2, No. 5, 2000

tivity to give only one isomer, 1,3-di-tert-butyl-5-methyl-
benzene (7a) or 1,3-diphenyl-5-methylbenzene (7b), in 47%
and 31% yield, respectively.
1-halo-1,4-pentadienes with alkynes afforded polysubstituted
benzenes, which might proceed via a similar intermediate
to 9.14 The consecutive insertion of the second alkyne and
the intramolecular carbon-carbon double bond would gener-
ate 11. The â-hydrogen elimination from 11 would give the
palladium hydride complex 13 and the cyclized product 12,
which isomerizes immediately to the benzene derivative 3
or 7. The elimination of HOTs from 13 would regenerate
Pd(0).15 Other possibilities are a [2 + 2 + 2] cycloaddition16
via 14 (Scheme 2, route A) and a similar mechanism to
Scheme 2
To ascertain whether a π-allylpalladium complex is an
intermediate in the catalytic benzannulation as well as the
stoichiometric one, an NMR experiment was carried out (eq
6). Oxidative addition of allyl tosylate to Pd(0) proceeded
smoothly in CDCl3 at room temperature even in the presence
of 2a. The π-allyl complex 8 was observed in the 1H NMR
spectrum of the reaction mixture, without any indication of
other complex formation.12 Further, this reaction mixture
gave 3a on heating at 80 °C.
Scheme 1 through 9′, which could be generated from 1517
by â-elimination of tosylate (route B). If the present
benzannulation proceeds through 14 or 9′, benzene deriva-
tives 16 should be produced. The reaction of 5a or 5b with
2a, however, does not produce 16 only the isomers 6a or
6b, respectively. These and the above-mentioned NMR
experiment indicate that the π-allylpalladium 8′ is more
reasonable as the reaction intermediate than 14 and 15,
although other mechanisms cannot be ruled out completely.
The following is a plausible mechanism of the reaction
(Scheme 1). Oxidative addition of allyl tosylate to Pd(0)
The transition metal mediated synthesis of aromatic rings
is mainly accomplished by cyclotrimerization of alkynes.
However, when two or three different alkynes were used to
prepare a penta- and a trisubstituted benzene, a mixture of
several benzene derivatives was obtained in most cases.18,19
The reaction reported here further develops the chemistry
of π-allylpalladium and is a convenient route to polysubsti-
tuted benzenes.
Scheme 1
Supporting Information Available: Experimental pro-
cedures and analytical and spectroscopic data of compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL991406N
(17) Trost, B. M.; Tanoury, G. J. J. Am. Chem. Soc. 1987, 109, 4753.
(18) Reviews: (a) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984,
23, 539. (b) Schore, N. E. Chem. ReV. 1988, 88, 1081. (c) Collman, J. P.;
Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications of
Organotransition Metal Chemistry; University Science Books: Mill Valley,
CA, 1987; p 870.
(19) For examples of recent progress in transition metal mediated
selective benzannulation, see: (a) Saito, S.; Salter, M. M.; Gevorgyan, V.;
Tsuboya, N.; Tando, K.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 3970.
(b) Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima, K.; Kotora,
M. J. Am. Chem. Soc. 1998, 120, 1672. (c) Mori, N.; Ikeda, S.; Sato, Y. J.
Am. Chem. Soc. 1999, 121, 2722.
generates the π-allylpalladium complex 8′. Insertion of an
alkyne to the Pd-allyl bond of 8′ would afford 9.13 Negishi
briefly reported that the palladium-catalyzed reactions of
Org. Lett., Vol. 2, No. 5, 2000
657