A novel Nickel(0)-mediated one-pot cascade reaction to cis-9,10- dihydroxy-9,10-dihydrophenanthrenes and 9-phenanthrones

Full text of DOI:10.1021/jo9817523

J . Org. Chem. 1999, 64, 655-658
655
A Novel Nick el(0)-Med ia ted On e-P ot
Ca sca d e Rea ction to cis-9,10-Dih yd r oxy-
9,10-d ih yd r op h en a n th r en es a n d
9-P h en a n th r on es
Helge A. Reisch, Volker Enkelmann, and Ullrich Scherf*
Max-Planck-Institut fu¨r Polymerforschung,
Ackermannweg 10, D-55128 Mainz, Germany
Received August 26, 1998
In tr od u ction
Ni(0)-mediated aryl-aryl homocouplings of haloaryl
compounds represent a highly potent, very efficient
method for the synthesis of biaryls and oligo- or polyaryls.
The method is applicable in the presence of a broad
variety of additional functional groups (e.g., ether, alde-
hyde, keto, amino, and nitro substituents) which remain
unreacted after the aryl-aryl coupling.1 The original
variant for this homocoupling of arylhalides, described
by Semmelhack et al., is based on stoichiometric amounts
of preformed Ni(0) reagents.2 This procedure was ex-
tended to Ni(0) reagents generated in situ3 and also
adapted to catalytic amounts of Ni(0) reagents in the
presence of an additional reducing agent.4 Yamamoto et
al. described the application of this efficient coupling
reaction on the synthesis of polyaryls starting from bihalo
monomers, by means of 1.2 equiv of the Ni(COD)2 reagent
per aryl-aryl bond formed.5
F igu r e 1. Poly(p-phenacene).
pinacolones 4 during an acidic workup procedure. Thus,
the phenanthrone derivatives 4a and 4b are available
in high yields starting from the corresponding 2-bro-
mobenzophenones 1a and 1b in a one-pot reaction.
Our experiments were part of a project dealing with
the synthesis of low-molecular-weight model compounds
of poly(p-phenacene) ladder polymers6 (Figure 1), fully
aromatic ribbon polymers which were synthesized in
1993 by Chmil and Scherf. The ladder polymers were
generated in a two-step reaction sequence involving an
aryl-aryl coupling according to Yamamoto5 followed by
a polymer-analogous olefination of the keto functions.
First, we have tried to synthesize the diketo model
compound 2a under the conditions of the polymer reac-
tion, using a slight excess of the transition-metal reagent
Ni(COD)2 (1.2 equiv per aryl-aryl bond), together with
2,2′-bipyridine and 1,5-cyclooctadiene as coreagents. For
this, a solution of the bromo compound 1a dissolved in
dry DMF was added to the purple solution of the nickel
complex in dry DMF at 60 °C. After acidic workup, the
expected aryl-aryl coupled diketone 2a was obtained in
78% yield. However, we could isolate a byproduct in about
20% yield, which was unambiguously identified as the
pinacolone 4a . This unexpected result implies that the
initial aryl-aryl coupling product can undergo a further
intramolecular cyclization to the pinacol 3a (Scheme 1)
under the reaction conditions of the Ni(0)-mediated aryl-
aryl coupling. The pinacolone 4a was then generated
during the acidic workup with 2 N HCl. To explore the
synthetic scope of this cascade reaction in more detail,
we have reacted the 2-bromobenzophenone derivatives
1a,b and 2-bromobenzaldehyde (1c) with varying amounts
of Ni(COD)2.
Resu lts a n d Discu ssion
In this note, we describe homocoupling experiments of
2-carbonyl-substituted bromobenzenes 1 with an excess
(1.2-2.2 equiv per aryl-aryl bond formed) of the Ni(COD)2
reagent. For this variant of the coupling reaction, the 2,2′-
keto- or aldehyde-substituted biphenyls 2 generated in
the initial aryl-aryl coupling step do not represent the
final reaction products. The aryl-aryl coupled intermedi-
ates undergo a subsequent intramolecular pinacol-type
cyclization which leads stereoselectively to cis-9,10-
dihydroxy-9,10-dihydrophenanthrene derivatives 3. Both
reaction steps of this one-pot reaction cascade are effected
by the Ni(COD)2 reagent. The novel reaction sequence
provides the cyclic products 3 in excellent yields of up to
98%, representing, therefore, a very simple one-pot
method for the generation of cis-9,10-dihydroxy-9,10-
dihydrophenanthrenes 3. If the substituents R at the 9-
and 10-positions of the phenanthrene skeleton are char-
acterized by an additional tendency to undergo acid-
catalyzed cationic rearrangements, the resulting pinacols
3 can be completely converted into the corresponding
The results of this reaction series are listed in Table
1. To prevent the pinacol-pinacolone rearrangement of
3 to 4, we have applied a modified neutral, nonacidic
workup procedure (for details see Experimental Section).
Under these reaction conditions, the reaction mixtures
were composed only of the pinacols 3 and the diketones
2 as products (entries 1-3). The product ratio 3/2 was
in each case about 20:80 if 1.2 equiv of Ni(COD)2 per
aryl-aryl bond was used. When the amount of the
Ni(COD)2 reagent was increased to 2.2 equiv, formation
of the pinacol 3 becomes the dominant reaction. Hereby,
in a first variant, the bromo compounds 1a -c were added
in one portion to the solution of the nickel complex. The
* E-mail: scherf@mpip-mainz.mpg.de. Tel: +49-6131-379306.
Fax: +49-6131-379100.
(1) Wilke, G. The Organic Chemistry of Nickel; Academic Press: New
York, 1975; Vol. II, p 246.
(2) Semmelhack, M. F.; Helquist, P. M.; J ones, L. D. J . Am. Chem.
Soc. 1971, 93, 5908.
(3) Kende, A. S.; Liebeskind, L. S.; Braitsch, D. M. Tetrahedron Lett.
1975, 3375.
(4) Colon, I.; Kelsey, D. R. J . Org. Chem. 1986, 51, 2627.
(5) Yamamoto, T.; Morita, A.; Miyazaki, Y.; Maruyama, T.; Wakaya-
ma, H.; Zhou, Z.; Nakamura, Y.; Kanbara, T.; Sasaki, S.; Kubota, K.
Macromolecules 1992, 25, 1214-1223.
(6) Scherf, U.; Chmil, K. Acta Polym. 1997, 48, 208.
10.1021/jo9817523 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/29/1998

656 J . Org. Chem., Vol. 64, No. 2, 1999
Notes
Sch em e 1. Rea ction Sch em e of th e
Nick el(0)-Med ia ted Ca sca d e Rea ction
F igu r e 2. X-ray structure of cis-9,10-dihydroxy-9,10-dihy-
drophenanthrene (3b).
Sch em e 2. In tr a m olecu la r Cycliza tion of 2a -c to
th e cis-P in a cols 3a -c
Ta ble 1. Rea ction Da ta of th e Ca sca d e Rea ction of 1a -c
to 2a -c/3a -c
Ni(COD)2
(equiv)
total yield
2 and 3 (%)
entry no
R
ratio 2:3 (%)
1
2
3
4
5
6
7
8
9
a
b
c
a
b
c
a
b
c
1.2a
1.2a
1.2a
2.2a
2.2a
2.2a
2.2b
2.2b
2.2b
92
96
96
94
97
99
97
99
100
78:22
76:24
84:16
9:91
10:90
17:83
0:100
0:100
8:92
these shortcomings, we have crystallized 3b and verified
its structure by X-ray crystal structure analysis. As a
result, we could characterize compound 3b as the cis-
isomer (Figure 2). This cis-configuration of 3b is a clear
indication that the cyclization step of 2b to 3b should
involve a cyclic intermediate in which a Ni(0) center
coordinates two carbonyl functions. To prove this mecha-
nistic assumption, we have also reacted the preformed
2,2′-substituted biphenyls 2a -c with 1.2 equiv of
Ni(COD)2. In this case, we could isolate the intramolecu-
larly cyclized pinacols 3a -c in nearly quantitative yields,
as expected (Scheme 2).
The proposed mechanism for the Ni(0)-mediated cy-
clization is shown in Scheme 3. On the basis of our
findings, the reaction sequence starting from 1a -c
involves two reaction steps: (1) formation of the 2,2′-
substituted biphenyl intermediates via aryl-aryl cou-
pling and (2) intramolecular cyclization to the corre-
sponding pinacols.
a
b
Addition of the bromo compound in one portion. Slow addi-
tion of the bromo compound over a time period of 20 min.
pinacols 3 were then obtained in rather high yields of
83-91% (entry 4-6). These yields could be further
improved in a slightly varied reaction methodology in
which the educts 1a -c are slowly added to the solution
of the Ni(0) reagent. For this special variant, the phenyl
substituted products 3a ,b could be isolated in nearly
quantitative yields, and the unsubstituted phenanthrene
pinacol 3c in almost 92% yield (entries 7-9). Monitoring
the progress of the reaction by HPLC, we have found that
the two-step reaction proceeds very fast and is almost
completed after 4-5 min.
We have also investigated whether the above-described
intramolecular Ni(0)-mediated pinacol cyclization can
also proceed as an intermolecular process starting from
aromatic ketones or benzaldehyde. Unfortunately, all
attempts to couple such carbonyl compounds failed, and
we always isolated the unreacted educts (Scheme 4).
Therefore, the Ni(0)-mediated pinacol cyclization seems
to be restricted to intramolecular cyclizations, e.g., that
of 2,2′-substituted biaryls.
The cyclization can lead, in principle, to the cis- or
trans-configured product 3. However, the 1H and 13C
spectra indicate that only one of the two possible isomers
is formed. The formation of the pinacols is, therefore,
highly stereoselective. Because both of the stereoisomeres
of pinacol 3c (R ) H) were described in the literature,
we have initially concentrated on the structural analysis
of 3c. However, the literature data for cis- and trans-3c
are not consistent, the melting points given for trans-3c
differ, for example, by more than 30 °C.7 To overcome
Con clu sion
The 2-bromobenzophenones 1a ,b and 2-bromobenzal-
dehyde (1c) can be transformed to the pinacols 3a -c in
(7) Platt, K. L.; Oesch, F. Synthesis 1982, 459. Miura, R.; Honmaru,
S.; Nakazaki, M. Tetrahedron Lett. 1968, 50, 5271.

Notes
J . Org. Chem., Vol. 64, No. 2, 1999 657
Sch em e 3. P r op osed Mech a n ism for th e F or m a tion of th e P in a cols 3 fr om th e Bip h en yl In ter m ed ia tes 2
Hz, 4J ) 1.8 Hz, 1H), 7.20 (d, 3J ) 8.0 Hz, 2H), 2.35 (s, 3H,
-CH3). 13C NMR (125 MHz, C2D2Cl4): δ ) 195.8, 145.3, 141.0,
133.8, 133.5, 131.5, 130.6, 129.7, 129.3, 127.5, 119.7, 22.2. FD-
MS: m/z ) 275.9. Anal. Calcd for C14H11BrO (275.1): C, 61.11;
H, 4.03; Br, 29.04. Found: C, 61.01; H, 4.03; Br, 28,73.
Sch em e 4. Rea ction of Ar om a tic Keton es a n d
Ben za ld eh yd e w ith Ni(COD)2
2-Br om o-3′,4′-d ih exyloxyben zop h en on e (1b). The reaction
of 2-bromobenzoyl chloride with 1,2-dihexyloxybenzene was
performed as described for 1b. Recrystallization from methanol
gave 1a in 82% yield. Mp: 48-49 °C. 1H NMR (500 MHz,
C2D2Cl4): δ ) 7.59 (dd, 3J ) 7.9 Hz, 4J ) 1.0 Hz, 1H), 7.42 (d,
3
4
4J ) 2.0 Hz, 1H), 7.36 (dt, J ) 7.5 Hz, J ) 1.0 Hz, 1H,), 7.30
(dd, 3J ) 7.8 Hz, 4J ) 1.8 Hz, 1H), 7.28 (dt, 3J ) 7.4 Hz, 4J )
a one-pot, nickel(0)-mediated cascade reaction in excel-
lent yields. The reaction occurs stereoselectively, and only
the cis-diol was isolated. The corresponding pinacolones
4a ,b have been obtained under acid workup conditions.
The novel reaction sequence defines an efficient synthetic
method for the generation of cis-9,10-dihydroxy-9,10-
dihydrophenanthrenes and the corresponding 9-phenan-
thrones in a one-pot process. However, the Ni(0)-
mediated pinacol cyclization as second step of the reaction
sequence is restricted to intramolecular processes. Ben-
zaldehyde or aromatic ketones do not yield the corre-
sponding pinacols when reacted with Ni(COD)2. Further
studies are planned to carry out the novel cascade
reaction with catalytic amounts of the Ni(0) complex in
the presence of an additonal reducing agent (e.g., Zn).
3
4
3
1.8 Hz, 1H), 7.13 (dd, J ) 8.4 Hz, J ) 2.0 Hz, 1H), 6.76 (d, J
) 8.5 Hz), 3.97 (m, 4H), 1.76 (m, 4H), 1.29 (m, 8H), 0.85 (m,
6H). 13C NMR (125 MHz, C2D2Cl4): δ ) 194.8, 154.8, 149.4,
141.2, 133.4, 131.2, 129.2, 129.1, 127.5, 126.6, 119.8, 114.2, 112.1,
69.8, 69.4, 31.9, 31.8, 29.5, 29.3, 26.0, 22.9, 14.3. FD-MS: m/z )
461.4. Anal. Calcd for C25H33BrO3 (460.2): C, 65.07; H, 7.21; Br,
17.32. Found: C, 64.95; H, 7.08; Br, 16,85.
ci s-9,10-D ih y d r o x y -9,10-b is (4-m e t h y lp h e n y l)p h e n -
a n th r en e (3b) (Sta n d a r d P r oced u r e). Ni(COD)2 (1.59 g, 6.0
mmol), 1,5-cyclooctadiene (531 mg, 5.0 mmol), and bipyridine
(937 mg, 6.0 mmol) were dissolved in 20 mL of dry DMF in a
Schlenk tube under argon. 2-Bromo-4′-methylbenzophenone (1b)
(1.37 g, 5.0 mmol) was added to the solution at room tempera-
ture. The reaction mixture was stirred at 60 °C for 3 h. After
cooling to room temperature, the mixture was diluted with
methylene chloride, filtered through a small pad of silica gel,
and washed three times with a 10% aqueous solution of FeCl3.
The organic layer was separated and dried over MgSO4. The
solvent was removed in vacuo, and the crude product was
purified by column chromatography on silica gel (ethyl acetate/
hexane, 1/4) to yield 3b (0.97 g, 99%).8 Mp: 186-187 °C (decomp.
Exp er im en ta l Section
2-Bromobenzaldehyde and 2-bromobenzoyl chloride were
obtained from Aldrich and were used without further purifica-
tion. The melting points are not corrected.
X-r a y Cr ysta llogr a p h y. Data were collected on a diffracto-
meter with graphite monochromated Mo KR radiation (λ )
0.71069 Å) at 210 K. The structure was solved by direct methods
(SIR92) and refined by full-matrix least-squares analyses with
anisotropic temperature factors for C and O. The H atoms were
refined with fixed isotropic temperature factors in the riding
mode. No absorption correction was applied.
3
1H NMR (500 MHz, C6D4Cl2, 438 K): δ ) 7.92 (d, J ) 7.8 Hz,
2H), 7.39 (t, 3J ) 7.8 Hz, 2H, H-3), 7.33 (d, 3J ) 7.6 Hz, 2H),
3
3
7.21 (t, J ) 7.6 Hz, 2H), 6.80 (d, 3J ) 8.0 Hz, 4H), 6.74 (d, J )
7.9 Hz, 4H), 3.0 (s, 2H), 2.25 (s, 6H). FD-MS: m/z ) 392.4. Anal.
Calcd for C28H24O2 (392.5): C, 85.86; H, 6.16. Found: C, 85.62;
H, 6.03. Crystal data for 3b (crystallized from methanol):
C28H24O2, monoclinic, space group P21; a ) 10.2647(6), b )
9.7202(3), c ) 10.8440(6) Å; â ) 101.719(2)°, V ) 1059.4 Å3, Z )
2, Dx ) 1.230, m(MoKR) ) 0.707 cm-1. A crystal with dimensions
0.4 × 0.25 × 0.1 mm3 was used for the data collection. In
addition, 2429 unique reflections were measured, of which 1975
were observed (I > 3σ(I)). R ) 0.044, Rw ) 0.042 (unit weights).
ci s-9,10-D ih y d r o x y -9,10-b is (3,4-d ih e x y lo x y p h e n y l)-
p h en a n th r en e (3a ). Using our standard procedure, the cou-
pling of 1a (1.04 g, 2.25 mmol) gave 3a (0.85 g, 97%),8 which
2-Br om o-4′-m eth ylben zop h en on e (1b). A solution of an-
hydrous AlCl3 (4.0 g, 30 mmol) in 50 mL of toluene at 0 °C was
treated with a solution of 2-bromobenzoyl chloride (5.0 g, 28
mmol) in 20 mL of methylene chloride. The resulting mixture
was stirred at 25 °C for 24 h, poured into 30 g of ice, and
extracted with CH2Cl2. The organic phase was washed several
times with diluted hydrochloric acid and H2O. After drying over
MgSO4, concentration in vacuo, and recrystallization from
hexane, 1b was obtained (5.76 g, 92%). Mp: 91 °C. 1H NMR
(8) The products 3a and 3b exhibit complex 13C NMR spectra at
ambient temperature, suggesting that the rotation of the aryl rings in
the 9- and 10-positions of the phenanthrene skeleton is restricted. Even
at 165 °C in 1,4-C6D4Cl2, we could not obtain well-resolved 13C NMR
spectra.
3
3
(500 MHz, C2D2Cl4): δ ) 7.61 (d, J ) 8.0 Hz, 2H), 7.58 (dd, J
4
3
4
) 7.6 Hz, J ) 1.0 Hz, 1H,), 7.35 (dt, J ) 7.6 Hz, J ) 1.0 Hz,
1H), 7.29 (dt, 3J ) 7.6 Hz, 4J ) 1.8 Hz, 1H), 7.25 (dd, 3J ) 7.6

658 J . Org. Chem., Vol. 64, No. 2, 1999
Notes
was purifed by column chromatography (ethyl acetate/hexane,
1H), 7.89 (d, 3J ) 7.8 Hz, 1H), 7.86 (d, 3J ) 8.0 Hz, 1H), 7.53
(dd, 3J ) 8.0 Hz, 3J ) 7.6 Hz, 1H), 7.37 (dd, 3J ) 8.0 Hz, 3J )
7.2 Hz, 1H), 7.31 (dd, 3J ) 7.8 Hz, 3J ) 7.6 Hz, 1H), 7.22 (dd, 3J
) 7.8 Hz, 3J ) 7.2 Hz, 1H), 6.84 (d, 3J ) 7.8 Hz, 1H), 6.71 (d, 3J
1
1/10). Mp: 74-76 °C. H NMR (500 MHz, p-C6D4Cl2, 438 K): δ
) 7.85 (d, 3J ) 6.3 Hz, 1H), 7.74 (d, 3J ) 6.1 Hz, 1H), 7.60 (d, 3J
) 7.3 Hz, 1H), 7.19-7.14 (m, 2H), 7.03 (m, 1H), 6.94 (m, 2H),
3
6.67 (s, 2H), 6.62 (d, J ) 7.9 Hz, 2H), 6.51 (d, 3J ) 7.9 Hz, 2H),
4
3
) 8.5 Hz, 2H), 6.55 (d, J ) 2.0 Hz, 2H), 6.44 (dd, J ) 8.5 Hz,
3
3
4J ) 2.0 Hz, 2H), 3.95 (t, J ) 6.5 Hz, 4H), 3.80 (t, J ) 6.5 Hz,
4H), 1.74 (m, 4H), 1.62 (m, 4H), 1.37-1.28 (m, 24H), 0.92-0.87
(m, 12H). 13C NMR (125 MHz, C2D2Cl4, 135 °C): δ ) 200.1,
149.6, 149.5, 142.4, 137.1, 135.3, 133.8, 132.3, 131.8, 131.2, 128.6,
128.4, 128.2, 127.9, 124.2, 123.9, 122.9, 119.3, 115.2, 70.6, 70.1,
67.8, 31.8, 29.9, 29.8, 26.0, 25.9, 22.7, 22.6, 13.9. FD-MS: m/z )
746.5. Anal. Calcd for C50H66O5 (747.1): C, 80.39; H, 8.90.
Found: C, 80.26; H, 8.62.
3.76 (m, 8H), 1.55 (m, 8H), 1.31-1.14 (m, 24H), 0.73 (m, 12H).
FD-MS: m/z ) 764.2. Anal. Calcd for C50H68O6 (765.1): C, 78.49;
H, 8.92. Found: C, 78.32; H, 8.86.
cis-9,10-Dih yd r oxy-9,10-d ih yd r op h en a n th r en e (3c). Us-
ing our standard procedure, 2-bromobenzaldehyde (1.50 g, 8.11
mmol) was coupled to 3c (0.85 g, 100%), which was purifed by
column chromatography (ethyl acetate/hexane, 1/10). Mp: 180-
181 °C (decomp) (lit. 178-179 °C)9. 1H NMR (500 MHz,
CD2Cl2): δ ) 7.77 (d, 3J ) 7.7 Hz, 2H), 7.65 (d, 3J ) 7.7 Hz,
2H), 7.42-7.36 (m, 4H), 4.71 (s, 2H), 2.65 (s, 2H). 13C NMR (125
MHz, CD2Cl2): δ ) 136.8, 132.8, 128.7, 128.6, 125.6, 124.0, 74.3.
FD-MS: m/z ) 212.2. Anal. Calcd for C14H12O6 (210.2): C, 79.22;
H, 5.70. Found: C, 79.10; H, 5.76.
Acid ic Wor k u p for th e P r ep a r a tion of th e 9-P h en a n -
th r on es 4a /b. The reaction mixture, after the coupling of 1a or
1b, was poured into methanolic HCl, stirred for 24 h at 25 °C,
and extracted twice with methylene chloride. The organic phase
was washed with water and dried over MgSO4. Concentration
in vacuo, followed by recrystallization or column chromatography
gave the 9-phenanthrones 4a or 4b.
10,10-Bis(4-m eth ylp h en yl)-9-p h en a n th r on e (4b). Apply-
ing the acidic workup, followed by recrystallization from metha-
nol, we obtained 4b (0.90 g, 96%). Mp: 208-209 °C. 1H NMR
(500 MHz, C2D2Cl4): δ ) 7.93 (d, 3J ) 7.9 Hz, 1H), 7.85 (d, 3J )
7.9 Hz, 2H), 7.53 (m, 1H), 7.35 (m, 1H), 7.29 (m, 1H), 7.19 (m,
1H), 6.97 (d, 3J ) 8.2 Hz, 4H), 6.74 (d, 3J ) 8.2 Hz, 4H), 6.72 (d,
1H), 2.24 (s, 6H). 13C NMR (125 MHz, C2D2Cl4): δ ) 201.0, 141.8,
138.9, 137.2, 136.9, 134.3, 132.4, 131.2, 130.4, 130.3, 129.0, 128.8,
128.5, 128.2, 128.0, 124.4, 123.2, 67.8, 21.3. FD-MS: m/z ) 375.3.
Anal. Calcd for C28H22O0 (374.5): C, 89.81; H, 5.92. Found: C,
89.74; H, 5.88.
10,10-Bis(3,4-d ih exyloxyp h en yl)-9-p h en a n th r on e (4a ).
The acidic workup, followed by column chromatography (ethyl
acetate/hexane, 1/10), yielded 4a (1.0 g, 93%) as a viscous oil.
Ack n ow led gm en t. The authors would like to thank
Prof. Dr. Klaus Mu¨llen for generous support of this
study. Financial support for H.A.R. was given by the
Deutsche Forschungsgemeinschaft (DFG).
3
1H NMR (500 MHz, C2D2Cl4, 135 °C): δ ) 7.94 (d, J ) 8.0 Hz,
(9) Criegee, R.; Marchand, B.; Wannowius, A. Liebigs Ann. Chem.
1942, 550, 99.
J O9817523