Regioselective [2 + 2 + 2] cycloaddition of a nickel-benzyne complex with 1,3-diynes

Article abstract of DOI:10.1021/ol034720x

(Matrix presented) Reactions of nickel(0)-benzyne complexes with a range of symmetrically substituted 1,3-diynes in the presence of triethylphosphine lead to the regioselective formation of 2,3-dialkynyl naphthalenes. The regioselectivity can be reversed

Full text of DOI:10.1021/ol034720x

ORGANIC
LETTERS
2
003
Vol. 5, No. 14
477-2480
Regioselective [2 + 2 + 2]
Cycloaddition of a Nickel−Benzyne
Complex with 1,3-Diynes
2
Kimberly R. Deaton and Mary S. Gin*
Department of Chemistry, UniVersity of Illinois at Urbana-Champaign,
Urbana, Illinois 61801
mgin@scs.uiuc.edu
Received April 30, 2003
ABSTRACT
Reactions of nickel(0)−benzyne complexes with a range of symmetrically substituted 1,3-diynes in the presence of triethylphosphine lead to
the regioselective formation of 2,3-dialkynyl naphthalenes. The regioselectivity can be reversed when the diyne possesses substituents of
high steric bulk, allowing selective formation of either symmetric dialkynyl naphthalene.
6
The controlled synthesis of well-defined polyaromatic hydro-
carbons is an area of increasing interest due to the unique
electronic and materials properties of these compounds. Such
conjugated systems have found use as, inter alia, semi-
trimerization of alkynes, enynes, and/or diynes. Of these,
metal-catalyzed alkyne trimerization is particularly attractive
because of the ready availability of the alkyne precursors,
and the high degree of substitution obtained in the aromatic
products. An excellent example of this is the [2 + 2 + 2]
cycloaddition reaction developed by Bennett in which one
of the participating triple bonds is a nickel-benzyne complex
that reacts with 2 equiv of an alkyne to generate substituted
1
conductors in electronic devices, components of electronic
2
energy transfer systems, and fluorescent sensors of various
environmental changes.3
Given the diversity of materials that incorporate aromatic
rings, many methods exist for their construction from simpler
starting materials. These methods include functionalization
6
b,c
naphthalenes (eq 1).
3
4
of unsubstituted ring systems, cycloaromatization and
5
cyclocondensation reactions, as well as metal-catalyzed
(
1) (a) W u¨ rthner, F. Angew. Chem., Int. Ed. 2001, 40 (6), 1037.
(
b) Gundlach, D. J.; Nichols, J. A.; Zhou, L.; Jackson, T. N. Appl. Phys.
Lett. 2002, 80 (16), 2925. (c) Shtein, M.; Mapel, J.; Benziger, J. B.; Forrest,
S. R. Appl. Phys. Lett. 2002, 81 (2), 268.
(
2) (a) Tamura, M.; Gao, D.; Ueno, A. Chem. Eur. J. 2001, 7 (7), 1390.
(
2
b) Wang, X.; Levy, D. H.; Rubin, M. B.; Speiser, S. J. Phys. Chem. A
The extension of metal-mediated cycloaddition reactions
to include conjugated 1,3-diynes as substrates was historically
000, 104 (28), 6558.
3) (a) Isaev, R. N.; Ishkov, A. V.; Fisenko, O. V. J. Anal. Chem. 2001,
(
5
6 (12), 1095. (b) Hanhela, P. J.; Paul, D. B. Aust. J. Chem. 1981, 34,
1
687.
(5) (a) Qiao, X.; Padula, M. A.; Ho, D. M.; Vogelaar, N. J.; Schutt, C.
E.; Pascal, R. A., Jr. J. Am. Chem. Soc. 1996, 118 (4), 741. (b) Gribble, G.
W.; Sibi, M. P.; Kumar, S.; Kelly, W. J. Synthesis 1983, 502. (c) Oku, A.;
Kakihana, T.; Hart, H. J. Am. Chem. Soc. 1967, 89 (17), 4554.
(4) (a) Wenk, H. H.; Winkler, M.; Sander, W. Angew. Chem., Int. Ed.
2
003, 42 (5), 502. (b) Zimmermann, G. Eur. J. Org. Chem. 2001, 457.
(c) Bowles, D. M.; Anthony, J. E. Org. Lett. 2000, 2 (1), 85.
1
0.1021/ol034720x CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/12/2003

limited by poor regioselectivity in the formation of benzene
products, accompanied by low yields due to polymerization
side reactions. Recent improvements in catalyst design have
Scheme 1. Mechanism of Nickel-Benzyne + Diyne
7
Cycloaddition
led to selective incorporation of 1,3-diynes into benzene
8
products, but such substrates have not been applied to the
cycloaddition with metal benzynes to form fused ring
products. Herein we report the first example of the regio-
selective reaction of nickel-benzynes 1 and 1,3-diynes 2 to
afford highly substituted dialkynyl naphthalenes (3, eq 2).
9
In our initial studies, nickel-benzyne 1a, prepared in situ
from nickel(II) complex 4, was reacted with 3,5-octadiyne
(2a) to give a mixture of two products (3a and 5, eq 3). The
diyne was quantitatively converted to the products, but
incorporation of the benzyne 1a was low (8% from 4). The
structures for 3a and 5 were assigned on the basis of the
1
presence or absence of symmetry evident in the H NMR
spectrum and the mass spectrometrically determined molec-
ular weights.
following reductive elimination of the zero-valent nickel
fragment NiL , affords the naphthalene product 3a. The
2
2
extruded nickel(0) (NiL ) is responsible for further trimer-
ization of the diyne to afford the benzene product 5.10
The low yield of naphthalene 3a isolated is attributed to
two factors: (1) the reduction of nickel(II) complex 4
proceeds in ca. 50% yield, affording the nickel-benzyne 1a
of variable purity, and (2) trimerization to form benzene 5
consumes the diyne at a faster rate than reaction with nickel-
benzyne 1a. To overcome these problems, we made two
changes. First, the more stable 4,5-difluorobenzyne nickel
The formation of these two products can be rationalized
6c
on the basis of the mechanism proposed for the nickel-
complex 1b was employed. In contrast to the nonfluorinated
complex 1a, complex 1b can be readily recrystallized and
even manipulated in air for brief periods of time. The second
improvement involved the addition of excess triethylphos-
phine to the reaction mixture to sequester the expelled
nickel(0), thus preventing the formation of the benzene
6
b,c
benzyne alkyne cycloaddition reaction (Scheme 1). Fol-
lowing coordination of the diyne 2a to give 6, alkyne
insertion into the benzyne-nickel bond gives nickelaindene
7
. Coordination to give 8 and insertion of a second equivalent
of diyne gives a seven-membered-ring metallacycle 9 that,
6b
product arising from diyne trimerization. Indeed, these two
changes led to the selective formation of 2,3-dialkynyl
naphthalene 3 as the major isolable product (Table 1).
(6) (a) Takahashi, T.; Li, Y.; Stepnicka, P.; Kitamura, M.; Liu, Y.;
Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 2002, 124 (4), 576. (b) Bennett,
M. A.; Wenger, E. Organometallics 1996, 15 (26), 5536. (c) Bennett, M.
A.; Wenger, E. Organometallics 1995, 14 (4), 1267. (d) Vollhardt, K. P.
C. Angew. Chem., Int. Ed. Engl. 1985, 23 (8), 539.
The reaction protocol involves adding freshly recrystallized
nickel benzyne 1b (1 equiv) to a solution of diyne 2
(
7) (a) H u¨ bel, W.; Mer e´ nyi, R. Chem. Ber. 1963, 96 (4), 930. (b) Hubert,
A. J.; Dale, J. J. Chem. Soc. 1965, 3160.
8) (a) Gevorgyan, V.; Radhakrishnan, U.; Takeda, A.; Rubina, M.;
(2.2 equiv) and triethylphosphine (5 equiv) in degassed
(
toluene under an atmosphere of argon. The solution is then
heated to 60 °C. Following removal of the solvent, the
Rubin, M.; Yamamoto, Y. J. Org. Chem. 2001, 66 (8), 2835. (b) Sugihara,
T.; Wakabayashi, A.; Nagai, Y.; Takao, H.; Imagawa, H.; Nishizawa, M.
Chem. Commun. 2002, 576.
(
9) Bennett, M. A.; Hambley, T. W.; Roberts, N. K.; Robertson, G. B.
Organometallics 1985, 4 (11), 1992.
(10) Chalk, A. J.; Jerussi, R. A. Tetrahedron Lett. 1972, 13 (1), 61.
Org. Lett., Vol. 5, No. 14, 2003
2
478

intriguing, as it indicates that the regioselectivity can be
controlled by judicious choice of diyne substitution.
Table 1. Nickel-Benzyne + 1,3-Diyne Cycloadditionsa
entry
diyne
R
product
% yield 3b
1
2b
2c
2d
2e
2f
2g
2h
2i
Ph
CO2Et
3b
3c
3d
3e
3f
3g
3h
3i
85
82
74
68
40
36
27
21
2c
3
4
5d
6
7
8
CH2CH2OTBS
n-Bu
CH2OMe
CH2CH2CO2Me
CH2OAc
The structural assignments of dialkynyl naphthalenes 3 and
1
SiMe3
10 were originally based primarily on the H NMR spectrum.
The number of signals revealed that symmetric products had
formed in both cases. Because of the proximity of the
a
Conditions: 1 equiv of 1b, 2.2 equiv of 2, 5 equiv of Et3P, toluene,
b
c
6
1
0 °C. Isolated yield. Reaction was performed at -78 to 23 °C with
0 equiv of 2c in the absence of Et3P. Et3P was omitted from the reaction.
d
1
,4-substituents to the 5,8-protons, the two constitutional
isomers can be distinguished by the different shielding effects
of an alkyl versus an alkynyl group. The observed chemical
shifts of δ 7.6-8.0 ppm for naphthalenes 3 are similar to
the shifts for H8 of 1-alkyl naphthalenes reported in the
products are purified by silica gel column chromatography
to give the dialkynyl naphthalenes 3 as yellow oils or white
solids. The highest yields of naphthalene were obtained using
diynes with relatively electroneutral phenyl (Table 1, entry
12
literature. In contrast, the δ 8.8 ppm shift observed for H8
13
in 10 is indicative of a 1,4-dialkynyl naphthalene.
1) or noncoordinating n-alkyl substituents (entries 3 and 4).
With the more reactive conjugated diester 2c, low yields were
initially obtained due to competitive decomposition of the
1
1
diyne. To circumvent this, the reaction was performed at
a lower temperature and the diyne was used in excess,
resulting in 82% yield of naphthalene 3c (entry 2). In some
cases (entries 2 and 5) triethylphosphine was not added, as
the diynes were reactive toward the phosphine.
We interpret the lower yields observed for entries 5-8 to
indicate restricted approach of diynes 2f-i to the metal
center. Of particular note is the lower yield for reaction of
diyne 2g (entry 6) when compared with the much higher
yield for 2d (entry 3), as the two diynes differ only in remote
To confirm our structural assignments further, we were
gratified to find that cycloadduct 3b formed a crystalline
product that could be analyzed by X-ray diffraction, which
confirmed our NMR structural analysis (Figure 1).
Because of its higher stability, the nickel-4,5-difluoro-
benzyne 1b could be isolated and purified, which enabled
the precise determination of the yield of the cycloaddition
reactions. However, the ability to access nonfluorinated
2 2 2 2 2
substituents (CH CH CO Me versus CH CH OTBS, respec-
tively). This suggests that the Lewis basic oxygens of the
esters in 2g coordinate to the metal center, preventing
productive reaction (vide supra, Scheme 1). Such side chain
coordination cannot occur with the sterically shielded oxygen
of 2d. This can also explain the lower yields observed for
the oxygen-containing methyl ether 2f (entry 5) and acetate
2h (entry 7). For trimethylsilyl-substituted diyne 2i, steric
2
,3-dialkynyl naphthalenes would constitute a more general
hindrance is likely the cause of the lower yield obtained
method. Knowing that 1,4-diphenylbutadiyne 2b gave the
highest yield of the cycloadduct, nickel-benzyne 1a, pre-
pared in situ from complex 4, was reacted with an excess of
(entry 8).
A further exploration of sterically demanding diyne
substituents led us to react 2,5-di-tert-butoxyhexadiyne 2j
with nickel-benzyne 1b. Although we were expecting little
or no yield of naphthalene product because of the steric
congestion at the terminal carbon of the diyne, we were
surprised to find that a 70% yield of the 1,4-dialkynyl
naphthalene 10 was formed (eq 4). This result is particularly
(12) (a) Rigaudy, J.; Lachgar, M.; Saad, M. M. A. Bull. Soc. Chim. Fr.
1994, 131 (2), 177. (b) Brown, R. F. C.; Browne, N. R.; Coulston, K. J.;
Eastwood, F. W. Aust. J. Chem. 1990, 43 (11), 1935. (c) Best, W. M.;
Collins, P. A.; McCulloch, R. K.; Wege, D. Aust. J. Chem. 1982, 35 (4),
8
43.
(13) (a) Pschirer, N. G.; Bunz, U. H. F. Tetrahedron Lett. 1999, 40 (13),
2
481. (b) John, J. A.; Tour, J. M. Tetrahedron 1997, 53 (45), 15515.
(
c) Butler, I. R.; Soucy-Breau, C. Can. J. Chem. 1991, 69 (7), 1117.
(11) Varela, J. A.; Castedo, L.; Maestro, M.; Mah ´ı a, J.; Sa a´ , C. Chem.
(d) Klusener, P. A. A.; Hanekamp, J. C.; Brandsma, L.; Schleyer, P. v. R.
Eur. J. 2001, 7 (23), 5203.
J. Org. Chem. 1990, 55 (4), 1311.
Org. Lett., Vol. 5, No. 14, 2003
2479

particular interest is the efficiency of fluorescence for phenyl-
susbtituted naphthalene 11. Whereas the majority of fluo-
rescence spectra were obtained at optical densities of 0.1,
naphthalene 11 required a 10-fold lower optical density in
order to stay within the limits of the detector, suggesting
that these may be useful fluorescent materials.
The observed regioselectivity for the nickel-benzyne +
diyne cycloaddition can be rationalized by considering the
electronic factors that influence the course of the reaction.
Because the benzyne carbon acts as the nucleophile toward
the electrophilic diyne, the regioselectivity of the reaction
is dictated by the relative sizes of the LUMO coefficients
on the diyne. For symmetric diynes, the electronic contribu-
tions of the conjugated bonds dominate over those of the
substitutents, placing the larger coefficient on the terminal
carbons of the diyne regardless of the substituents.14 Con-
sistent with this argument, we observe the same regioselec-
tivity with both electron-donating alkyl substituents (e.g.,
Table 1, entry 4) and electron-withdrawing ester groups
Figure 1. ORTEP diagram of 2,3-dialkynyl naphthalene 3b.
1,4-diphenylbutadiyne 2b, which afforded a 48% yield of
(Table 1, entry 2). The only exception occurs when the steric
1
1 for the two-step sequence (eq 5). As the reduction of
congestion at the more electrophilic site prohibits reaction
at that center (eq 4).
nickel(II) complex 4 to nickel(0)-benzyne 1a typically
proceeds in ca. 50% yield, this result indicates a high yield
for the cycloaddition reaction. Crystals of 11 were also
suitable for X-ray analysis, and the structure data obtained
was nearly identical to that of 3b (see Supporting Informa-
tion).
Although the electronic nature of the diyne substituents
does not affect the regioselectivity of the reaction, it does
influence the rate of reaction. This is most notable in the
case of diester 2c, which affords the naphthalene product 3c
after 4 h at -78 to 23 °C. In contrast, the more electron-
rich dibutyl diyne 2e yields naphthalene 3e after 4 h at
6
0 °C. Thus, not surprisingly, we observe that better
electrophiles react faster than less electrophilic diynes.
In conclusion, we have shown for the first time that
conjugated 1,3-diynes react regioselectively with nickel-
benzyne complexes in a formal [2 + 2 + 2] cycloaddition
reaction to give highly substituted dialkynyl naphthalenes.
The regiochemical course of the reaction is typically dictated
by the electronics of the diyne to afford 2,3-dialkynyl
naphthalenes; however, this electronic preference can be
overcome when the diyne substituents are particularly bulky,
resulting in the formation of 1,4-dialkynyl naphthalene. This
allows for the selective formation of either symmetric
dialkynyl naphthalene by simply choosing the appropriate
diyne substituent. The naphthalenes reported herein may find
utility as fluorescent materials, and further studies on their
photophysical properties are currently underway.
The dialkynyl naphthalene products are all chromophoric
and fluorescent, with absorption bands at 258-305 nm and
4
5
-1
-1
molar absorptivities of 3 × 10 -1.5 × 10 M cm (Figure
). The fluorescence emission bands appear at 363-407 nm
see Supporting Information for additional spectra). Of
2
(
Acknowledgment. Financial support from The donors of
the Petroleum Research Fund, administered by the American
Chemical Society (ACS-PRF # 36426-G1), and from the
University of Illinois is gratefully acknowledged.
Supporting Information Available: Experimental and
spectroscopic data for all new compounds and X-ray crystal-
lographic data for 3b and 11 (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
OL034720X
Figure 2. Absorption and emission spectra of 3e (-), 3c (- - -),
and 11 (‚‚‚) in chloroform.
(14) Varela, J. A.; Castedo, L.; Sa a´ , C. J. Am. Chem. Soc. 1998, 120
46), 12147.
(
2480
Org. Lett., Vol. 5, No. 14, 2003