First intermolecular regiospecific palladium-catalyzed enyne-diyne [4 + 2] cross-benzannulation reaction

Full text of DOI:10.1021/ja971935r

J. Am. Chem. Soc. 1997, 119, 11313-11314
11313
Communications to the Editor
First Intermolecular Regiospecific
Palladium-Catalyzed Enyne-Diyne [4 + 2]
(2)
Cross-Benzannulation Reaction
Vladimir Gevorgyan, Akira Takeda, and
Yoshinori Yamamoto*
Various different ways of the orientation of acetylenes are
possible for assembling an intermediate i, since three new bonds
4
are formed in [2 + 2 + 2] cyclotrimerization (eq 1). It occurred
Department of Chemistry, Graduate School of Science
to us that in the case where a conjugated enyne 3 would react
Tohoku UniVersity, Sendai 980-77, Japan
1
0
with alkyne in a [4 + 2] cycloaddition manner, this reaction
could be more regioselective than the [2 + 2 + 2] mode of
cycloaddition since only the regioselectivity of two bond
formation remains questionable. After trying a number of
alkynes in a role of enyne partner in the [4 + 2] cycloaddition,
we discovered that conjugated diynes 4 underwent regiospecific
cross-cycloaddition with 3. The reaction of 2-methyl-1-buten-
ReceiVed June 12, 1997
Since the earliest example of thermal trimerization of
acetylene to benzene reported by Berthelot in 1866, and the
1
first transition-metal-catalyzed version of this reaction demon-
2
strated by Reppe in 1948, the [2 + 2 + 2] cycloaddition of
acetylenes was extensively studied by number of research groups
and became a vast field three decades ago. A large number of
3
-yne (3a) with dodeca-5,7-diyne (4a) in the presence of 5 mol
1
3
3
% Pd(PPh ) in THF gave 5a in 89% yield (entry 1, Table 1).
transition metal catalysts, as well as Ziegler-type catalysts, give
3 4
rise to this reaction.4 Although this approach becomes one of
No traces of 6 were detected by NMR and capillary GLC
the most powerful methods to assemble a benzene ring, it suffers
from serious chemo- and regioselectivity problems which
normally lead to complex mixtures of products, thus severely
limiting the synthetic utility of this reaction (eq 1).5 Vollhardt
analyses of crude reaction mixtures. The enyne-diyne cross-
annulation reaction of enynes 3b,c appeared to be much faster
than the corresponding enyne-enyne homo-dimerization,14 thus
an equimolar amount of hexyl- (3b) and benzyl- (3c) enyne
reacted with 4a,b not only in regio-, but also in chemoselective
manner affording the cross-annulation products 5d-f, exclu-
sively (entries 4-6). In contrast, a 2-5-fold excess of volatile
and less-reactive 3a (toward diynes 4) was needed to drive the
reaction to complete conversion of 4 (entries 1-3).16 Bulky
diyne 4c reacted with enynes rather slower than 4a,b, thus the
slow addition of the enynes 3a,c was employed in order to avoid
its dimerization (entries 3 and 7).
(1)
succeeded to solve these problems for several types of intramo-
lecular 6 or partially intramolecular modes of cyclotrimeriza-
tion: three new bonds were formed under the cobalt catalysis
7
Apparently, the fact of regiospecific two bonds formation
affording cyclophane-type aromatic products in chemo- and
Two complementary regiospecific
intermolecular methods for constructing benzene skeleton under
regioselective manner.6
,7
(6) (a) Lecker, S. H.; Nguen, N. H.; Vollhardt, K. P. C. J. Am. Chem.
Soc. 1986, 108, 856. (b) Negishi, E.; Harring, L. S.; Owczarczyk, Z.;
Mohamud, M. M.; Ay, M. Tetrahedron Lett. 1992, 33, 3253. (c) For earlier
works, see also ref 4a and references cited therein.
(7) See, for example: (a) Halterman, R. L.; Nguyen, N. H.; Vollhardt,
K. P. C. J. Am. Chem. Soc. 1985, 107, 1379. (b) Berris, B. C.; Hovakeemian,
G. H.; Lai, Y.-H; Mestdagh, H.; Vollhardt, K. P. C. J. Am. Chem. Soc.
palladium catalysis were reported recently: the formation of
1
,3,5-unsymmetrical benzenes 1 Via cyclotrimerization of
8
terminal diynes and the synthesis of 1,4-disubstituted benzenes
2
9
Via [4 + 2] homo-dimerization of conjugated enynes. We
1
985, 107, 5670. (c) Helson, H. E.; Vollhardt, K. P. C.; Yang, Z.-Y. Angew.
Chem., Int. Ed. Engl. 1985, 24, 114. (d) Grigg, R.; Scott, R.; Stevenson, P.
Tetrahedron Lett. 1982, 23, 2691.
(8) Takeda, A.; Ohno, A.; Kadota, I.; Gevorgyan, V.; Yamamoto, Y. J.
Am. Chem. Soc. 1997, 119, 4547.
9) Saito, S.; Salter, M. M.; Gevorgyan, V.; Tsuboya, N.; Tando, K.;
Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 3970.
10) Although scattered data on related processes such as thermal
(
1
1,12
(
or
11
Lewis acid mediated intramolecular enyne-yne [4 + 2] cycloaddition
reactions were recently reported, the more synthetically useful intermolecular
now report the first example of intermolecular enyne-diyne
4 + 2] cross-benzannulation reaction: the reaction of enynes
with diynes 4 affording regioselectively 1,2,4-trisubstituted
13
enyne-yne cross-benzannulation still remained unemployed.
[
(11) Danheiser, R. L.; Gould, A. E.; Fernandez de la Predilla, R.;
Helgason, A. L. J. Org. Chem. 1994, 59, 5514.
3
(
12) Burrell, R. C.; Daoust, K. J.; Bradley, A. Z.; DiRico, K. J.; Johnson,
benzenes 5 in high to quantitative yields with none of the
regioisomers 6 being produced (eq 2).
R. P. J. Am. Chem. Soc. 1996, 118, 4218.
(13) The structure of para-oriented 5 was unambiguously confirmed by
00 MHz NOE and COLOC NMR analyses. For details see the Supporting
5
(
1) Berthelot, M. C. R. Acad. Sci. 1866, 62, 905.
Information.
(
2) Reppe, W.; Schlichting, O.; Klager, K.; Toepel, T. Justus Liebigs
(14) The homo-dimerization of enynes has been recently reported, see
ref 9.
Ann. Chem. 1948, 560, 1.
(3) (a) Meriwether, L. S.; Clothup, E. C.; Kennerly, G. W.; Reusch, R.
(15) The preparation of 5a is representative. A mixtute of 3a (0.6 mmol),
4a (0.5 mmol), and Pd(PPh3)4 (5 mol %) in THF (2 mL) was refluxed
under an argon atmosphere. Reaction course was monitored by capillary
GLC analysis. After the reaction was complete (12 h for 5a), the mixture
was filtered through a short column (silica gel) and concentrated. Purification
by column chromatography (silica gel, hexane eluent) gave 101 mg of 5a
(89%) and 8 mg of 4a (10%). The good scalability of this reaction was
demonstrated with an essentially quantitative preparation of 5b (homoge-
N. J. Org. Chem. 1961, 26, 5155. (b) Reikhstel’d, V. O.; Makovetskii, K.
L. Russ. Chem. ReV. 1966, 35, 510.
(
4) For recent reviews, see: (a) Vollhardt, K. P. C. Angew. Chem., Int.
Ed. Engl. 1984, 23, 539-644. (b) Schore, N. E. Chem. ReV. 1988, 88, 1081-
119. (c) Trost, B. M. Science 1991, 254, 1471-1477. (d) Lautens, M.;
Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-92.
5) See, for example: (a) Colman, J. P.; Kang, J. W.; Little, W. F.;
1
(
1
Sullivan, M. F. Inorg. Chem. 1968, 7, 1298. (b) Ferreri, R. A.; Wolf, A. P.
J. Phys. Chem. 1984, 88, 2256. (c) Borrini, A.; Diversi, P.; Ingrosso, G.;
Lucherini, A.; Serra, G. J. Mol. Catal. 1985, 30, 181. (d) Yasuda, H.;
Nakamura, A. ReV. Chem. Intermed. 1986, 6, 365.
neous by H NMR and GLC analyses, isolated yield) in a 5 mmol scale
under the mentioned reaction conditions.
(16) The excess of enyne 3a underwent homo-dimerization, affording
2, see also footnote c of Table 1.
S0002-7863(97)01935-5 CCC: $14.00 © 1997 American Chemical Society

11314 J. Am. Chem. Soc., Vol. 119, No. 46, 1997
Communications to the Editor
Table 1. Palladium Catalyzed Enyne-Diyne
regiospecific formation of para-oriented regioisomer 5, encour-
aged us to propose the following mechanistic rationale for this
reaction (eq 5). The reversible coordination of palladium with
1
5
Cross-Benzannulation
(5)
enyne and diyne 7 would produce palladacycle 8,18 stabilized
3
by coordination of Pd atom with neighboring η -propargyl
19
moiety. The reductive elimination of palladium from 8 would
2
0
form strained cyclic cumulene 9, which Via sigmatropic
rearrangement would be transformed into cross-annulation
product 5h.
As a final remark on our investigation, we disclose our initial
experiments on palladium-catalyzed enyne-triyne cross-ben-
zannulation (eq 6). We found that 3c reacted selectively with
terminal triple bond of bis-silyl-triyne 10 producing synthetically
21
useful silylated diyne 11 as a sole product in excellent chemical
yield (eq 4).
(6)
Although further investigation to settle a precise reaction
mechanism is needed, the present procedure provides a new
regiospecific and synthetically useful route to 1,2,4-trisubstituted
benzenes.
a
Isolated yields based on diyne 4, except for where otherwise
b
c
indicated. Two equivalents of 3a were utilized. Excess of 3a
underwent homodimerization affording the byproduct 2.
of 4 (%). Five equivalents of 3a were utilized. Compound 3 was
added in five portions. NMR yield. One-half equivalents of 3c were
added in 10 portions. Two and a half equivalents of 3c were added
during 14 h with syringe pump.
9
d
Recovery
e
f
Supporting Information Available: Spectroscopic and analytical
data for compounds 5a-k and 11 (21 pages). See any current masthead
page for ordering and Internet access instructions.
g
h
i
JA971935R
1
7
observed in all cases of enyne-diyne cycloaddition reactions
eq 2, Table 1) eliminated involvement of the traditional
transition-metal-assisted mechanism of alkynes trimerization (eq
).4 Indeed, if the mentioned mechanism is operative, the
(17) The reaction of 3a with terminal unsymmetric diyne 4d produced
(
5j in 50% yield (NMR) along with a minor product 5k (28% by NMR).
This indicates that both triple bonds of 4d could act as an enynophile and
thus the regioselectivity in this case is not perfect.
1
formation of the two regioisomers 5 and 6 is unavoidable. As
a part of mechanistic study of this palladium-catalyzed enyne-
diyne cross-benzannulation, the deuterium analogues 3d,e were
employed in the reaction with diyne 4a. Accordingly, the cross-
benzannulation of 3d afforded 5h in 64% yield with a deuterium
atom attached to the C-6 position of benzene ring (eq 3), and
cycloaddition of 3e gave 5i (eq 4) in 61% yield with deuterium
atoms at C-3 and C-5 positions of ring, exclusively. The results
(
18) π-Propargyl palladium complexes have been recently isolated and
fully characterized. See: (a) Ogoshi, S.; Tsutsumi, K.; Kurosawa, H. J.
Organomet. Chem. 1995, 493, C19. (b) Ogoshi, S.; Tsutsumi, K.; Ooi, M.;
Kurosawa, H. J. Am. Chem. Soc. 1995, 117, 10415.
(
19) The coordination of palladium to propargyl group in the intermediate
8
is supported not only by the exclusive formation of a sole regioisomer 5
but also by the fact that simple alkynes, such as acetylene and its alkyl-,
aryl-, halo-, and cyanoderivatives, which do not posses such an additional
alkynyl group, do not act as enynophiles in the mentioned reaction at all.
Accordingly, an alternative explanation of remarkable reactivity of diynes
in terms of steric effects was discounted by the observation that acetylene
itself did not act as an enynophile in that reaction.
(3)
(
20) This type of 6-membered strained cyclic cumulene has been recently
proposed as an intermediate in the dehydro Diels-Alder cycloadditions.
a) For a review, see: Johnson, R. P. Chem. ReV. 1989, 89, 1111. (b) See
(
also ref 12.
(21) Silyl-substituted aromatic alkynes and diynes are very useful building
(4)
blocks for assembling of conjugated oligo- and polyarylene ethynylenes.
For reviews, see: (a) Tour, J. M. Chem. ReV. 1996, 96, 537. (b) Harriman,
A.; Ziessel, R. J. Chem. Soc., Chem. Commun. 1996, 1707. See also: (c)
Ziessel, R.; Suffert, J. Tetrahedron Lett. 1996, 37, 2011. (d) Kitamura, T.;
Lee, C. H.; Taniguchi, Y.; Fujiwara, Y. J. Am. Chem. Soc. 1997, 119, 619.
on deuterium labeling experiments, taken together with the factof