A Novel Strategy for the Synthesis of Oxygenated Phenanthrenes Involving a Combination of Ullmann and McMurry Reactions

Article abstract of DOI:10.1021/jo982522r

A general synthetic procedure for the preparation of polyoxygenated phenanthrenes from substituted derivatives of benzaldehyde is described. The key compound is a 6,6′-biphenyl-1,1′-dicarboxaldehyde intermediate formed through an ambient temperature Ullmann coupling. The subsequent McMurry condensation gave rise to the phenanthrene in 45-57% yields.

Full text of DOI:10.1021/jo982522r

3650
J . Org. Chem. 1999, 64, 3650-3654
A Novel Str a tegy for th e Syn th esis of Oxygen a ted P h en a n th r en es
In volvin g a Com bin a tion of Ullm a n n a n d McMu r r y Rea ction s
Anne-Elisabeth Gies and Michel Pfeffer*
Laboratoire de Synthe`ses Me´tallo-Induites, UMR 7513 CNRS, Universite´ Louis Pasteur,
4 rue Blaise Pascal, 67070 Strasbourg, France
Received December 29, 1998
A general synthetic procedure for the preparation of polyoxygenated phenanthrenes from substituted
derivatives of benzaldehyde is described. The key compound is a 6,6′-biphenyl-1,1′-dicarboxaldehyde
intermediate formed through an ambient temperature Ullmann coupling. The subsequent McMurry
condensation gave rise to the phenanthrene in 45-57% yields.
Sch em e 1
In tr od u ction
For some years we have been interested in the pal-
ladium-induced synthesis of nitrogen heterocycles.1 In
this context, we recently studied the formation of com-
pounds which have structural analogy with the known
1c
Aporphine family of alkaloids.
Natural aporphines are phenanthrene-based hetero-
cycles with an original substitution pattern of hydroxyl,
methoxy, and methylenedioxy groups.2 Given their nu-
merous biological and therapeutic properties, many ef-
forts have focused on developing synthetic methods
toward this class of compounds.3 Our own strategy is
based on the insertion of a disubstituted alkyne in the
carbon-palladium bond of a 9-aminophenanthrene cy-
clopalladated complex.1c The extension of this methodol-
ogy to the preparation of natural product analogues
required a synthetically viable route to appropriately
substituted phenanthrene precursors, prior to the final
palladium-mediated step.
Despite the occurrence of the phenanthrene skeleton
in many natural products4a-c and the biological proper-
ties4d,e of these compounds, many of the reported syn-
thetic pathways to these polycylic aromatic hydrocarbons
are unsatisfactory.5 The classical obvious route utilizing
a Pschorr ring closure of stilbenes6a,b is usually poor
yielding (less than 10%). A more commonly used method
involves the oxidative photochemical ring closure of
stilbenes;6c-e however, it has many drawbacks such as a
limited success on a multigram scale and a lack of
selectivity, yielding mixtures of isomers. Pathways em-
ploying a precursor other than stilbene require harsh
conditions7a-c such as strong mineral acids and are often
restricted in terms of the substitution pattern.7d,e More-
over the requisite starting materials are often not readily
available.7f,g
In this paper, we propose an unprecedented retrosyn-
thetic approach toward the phenanthrene nucleus [Scheme
1]. It highlights the possibility of building the C(9)-C(10)
double bond during the last step of the process from a
suitably preformed biaryl. Formation of the latter was
achieved in a copper-mediated Ullmann aryl-aryl cou-
pling reaction. An obvious solution for the final step led
us to a novel application of the McMurry low valent
titanium (LVT) intramolecular condensation of 6,6′-
biphenyl-1,1′-dicarboxaldehydes (bisbenzaldehydes).
(1) (a) Pfeffer, M. Recl. Trav. Chem. Pays-Bas 1990, 109, 567-576.
(b) Pfeffer, M. Pure Appl. Chem. 1992, 64, 335-342. (c) Pfeffer, M.,
Beydoun, N. Synthesis 1990, 729-732. (c) Pfeffer, M.; Sutter-Beydoun,
N.; de Cian, A.; Fischer, J . J . Organomet. Chem. 1993, 453, 139-146.
(d) Spencer, J .; Pfeffer, M. Advances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; J AI Press: London, 1998; Vol. 6, pp 103-144.
(2) For general and updated information about the aporphines:
Guinaudeau, H.; Leboeuf, M.; Cave´, A. Lloydia 1975, 38, 275-338 and
references cited. (b) 1979, 42, 325-360; (c) 1983, 46, 761-835; (d) 1988,
51, 389-474; (e) 1994, 57, 1033-1135. See also, ref 3.
Resu lts a n d Discu ssion
Some years ago a modified ambient temperature Ull-
mann-type protocol was disclosed8 which afforded good
yields of bisbenzaldehydes under very mild experimental
conditions.9 Moreover, the methodology was compatible
with polyoxygenated substrates10a leading for instance
to 2a . Following this procedure we obtained the com-
(3) Southon, I. W.; Buckingham, J . Dictionary of Alkaloids; Chap-
man and Hall: New York, 1989.
(4) (a) Leong, Y. W.; Kang, C. C.; Harrison, L. J .; Powell, A. D.
Phytochem. 1997, 44, 157-165. (b) Majumder, P. L.; Banerjee, S.; Sen,
S. Phytochem. 1996, 42, 847-852. (c) Adam, K. P.; Becker, H.
Phytochem. 1994, 35, 139-143. (d) Castedo, L.; Tojo, G. The Alkaloids,
Chemistry and Physiology, Vol. XXXIX, Chapter III (Phenanthrene
alkaloids); Academic Press: San Diego, 1990. (e) Kende, A. S.; Curran,
D. P. J . Am. Chem. Soc. 1979, 101, 1857-1864.
(7) (a) Rahman, A. U.; Vuano, B. M.; Rodriguez, N. M. Aust. J . Chem.
1972, 25, 1521-1527. (b) Kobayashi, H. Bull. Chem. Soc. J pn. 1962,
35, 1970-1973. (c) Buu-Hoi, N. P.; Saint-Ruf, G. C. R. Acad. Sci. C
1965, 260, 593-596. (d) Ramana, M. M. V.; Potnis, P. V. J . Chem.
Res., Synop. 1996, 4, 175; J . Chem. Res., Miniprint 1996, 0979-0994.
(e) Turner, R. B.; Nettleton, D. E., J r.; Ferebee, R. J . Am. Chem. Soc.
1956, 78, 5923-5927. (f) Katritzky, A. R.; Zhang, G. F.; Xie, L. H. J .
Org. Chem. 1997, 62, 721-725. (g) Koo, S. H.; Liebeskind, L. S. J . Am.
Chem. Soc. 1995, 117, 3389-3404.
(5) For a general review, see: Floyd, A. J .; Dyke, S. F.; Ward, S. E.
Chem. Rev. 1976, 76, 509-562.
(6) (a) Wassmundt, F. W.; Kiesman, W. F. J . Org. Chem. 1995, 60,
196-201 and cited references. (b) Roblot, F.; Hocquemiller, R.; Cave´,
A. Bull. Soc. Chim. Fr. 1990, 127, 258-267. (c) Mallory, F. B.; Mallory,
C. Org. React. 1984, 30, 1-456. (d) Liu, L.; Yang, B.; Katz, T. J .;
Poindexter, M. K. J . Org. Chem. 1991, 56, 3769-3775. (e) Grimme,
S.; Pischel, I.; Nieger, M.; Vogtle, F. J . Chem. Soc., Perkin Trans. 2
1996, 2771-2774.
(8) Ziegler, F. E.; Chliwner, I.; Fowler, K. W.; Kanfer, S. J .; Kuo, S.
J .; Sinha, N. D. J . Am. Chem. Soc. 1980, 102, 790-798.
10.1021/jo982522r CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/27/1999

Synthesis of Oxygenated Phenanthrenes
J . Org. Chem., Vol. 64, No. 10, 1999 3651
Ta ble 1a
pounds depicted in the eq 1. The yield of 2a was increased
from 44% to 60% by changing the metalation time,
namely the lithiation of 1a with n-BuLi (50 min reaction
at -78 °C10b vs 20 min previously) and the subsequent
transmetalation with CuI. In the same manner, three
new compounds (2b-2d ) were also prepared. The 1H
NMR spectra of these compounds showed the expected
diastereotopy of the dioxomethylene protons due to the
restricted rotation around the congested aryl-aryl bond.
Moreover the compounds all display a W-coupling be-
tween the formyl protons and the H meta to it.
(1)
The bisbenzaldehydes 2a -2d obtained above were
subsequently submitted to a McMurry condensation.11
For this purpose we chose TiCl3‚DME3/2/Zn(Cu)12a which
led to the expected phenanthrenes, 3a -3c, in 45-57%
yields (see Table 1). These somehow moderate yields of
the cyclization reaction of 2a -2d could be due either to
traces of water or oxygen in the reaction medium or to
an unexpected sensitivity of the substrates or of the
intermediates (see below) to the presence of acidic TiCl3
that was not entirely reduced during the condensation
reaction according to the Fu¨rstner instant method.12b
However, this cyclization procedure could not be ap-
plied to the cyclization of 2d as it led to a mixture of
untractable products most probably due to side reactions
induced by the O-debenzylation reaction. This result was
a priori surprising since it was shown in several instances
that intramolecular McMurry couplings could be achieved
in the presence of benzyl-protected alcohols.13a,b However,
debenzylation reactions were observed recently when
performing the McMurry reaction in the presence of TiCl3
together with reducing agents such as Li, Mg, or Zn.14
Compounds 3a -3c have already been reported in the
literature 15a-e but they were insufficiently characterized.
We provide here full spectroscopic data (1H NMR, 13C
NMR) for all the phenanthrenes prepared.
The mechanism of the McMurry reaction is still not
well understood, but it is generally accepted13a that it
proceeds through a pinacol intermediate which undergoes
deoxygenation to the corresponding olefin. In many cases
the pinacol can be isolated.
We could never observed such intermediates, but we
were faced with an unexpected result for the intra-
molecular cyclization of the nonsymmetrical 2b. In this
single case, performing the reaction for 19 h or less led
to the isolation of two additional products together with
the expected 3,4-(methylenedioxy)phenanthrene 3b (eq
2). The characterization of these two side products 4b
and 5b was difficult as they were rather unstable and
difficult to handle, especially 5b; nevertheless they were
identified through their NMR and mass spectra as the
bisphenanthrenol 4b and the 9- or 10-phenanthrenol
5b.16 Notable features in the NMR spectra of 3b, 4b, and
5b were the following: for 3b, H9 and H10 were identified
as doublets (7.64 and 7.55 ppm) with a large coupling
constant of 9.0 Hz. In 5b the substitution of the double
bond by an OH group induced the neighboring enol
proton to be shifted to higher field (s, 6.96 ppm)16a while
a broad singlet (5.12 ppm) is attributed to the OH
proton.16b In the bisphenanthrenol derivative 4b a singlet
(9) The initial Ullmann reaction was performed in the presence of
copper metal around 200 °C for several hours. Ullmann, F.; Bielecki,
J . Chem. Ber. 1901, 34, 2174-2185.
(10) (a) Ziegler, F. E.; Fowler, K. W.; Rodgers, W. B.; Wester, R. T.
Org. Synth. 1987, 65, 108-118. (b) Ziegler, F. E.; Fowler, K. W. J .
Org. Chem. 1976, 41, 1564-1566.
(11) To our knowledge the McMurry condensation as a step in the
formation of the phenanthrene nucleus was limited to the synthesis
of the stilbene which was then cyclized by means of a photochemical
coupling: Merz, A.; Karl, A.; Futterer, T.; Stacherdinger, N.; Schneider,
O.; Lex, J .; Luboch, E.; Biernat, J . F. Liebigs Ann. Chem. 1994, 12,
1199-1209. See also: Ben, I.; Castedo, L.; Saa, J . M.; Seijas, J . A.;
Suau, R.; Tojo, G. J . Org. Chem. 1985, 50, 2236-2240. Experiments
using a LVT strategy to form compounds related to phenanthrenes
may be found in the two following papers: (a) Kadam, S. M.; Nayak,
S. K.; Banerji, A. Synth. Commun. 1995, 25, 135-142. (b) Yamamoto,
K.; Harada, T.; Okamoto, Y.; Chikamatsu, H.; Nakazaki, M.; Kai, Y.;
Nakao, T.; Tanaka, M.; Harada, S.; Kasai, N. J . Am. Chem. Soc. 1988,
110, 3578-3584.
(15) (a) Barger, G.; Weitnauer, G. Helv. Chim. Acta 1939, 22, 1036-
1047. (b) Konovalova, R. A.; Yunussov, S.; Orekhov, A. Bull. Soc. Chim.
Fr. 1940, 7, 70-77; Chemical Abstracts 1940, 34, 4072. (c) Shirai, H.;
Oda, N. Yakugaku Zasshi 1959, 79, 241-244; Chemical Abstracts 1959,
53, 13123. (d) Shirai, H.; Oda, N. Chem. Pharm. Bull. 1960, 8, 727-
731. (e) Dallacker, F.; Sommer, M.-T. Chem.-Ztg. 1984, 108, 329-331.
(16) (a) Nashed, N., T.; Bax, A.; Loncharich, R., J .; Sayer, J ., M.;
J erina, D., M. J . Am. Chem. Soc. 1993, 115, 1711-1722. (b) Due to its
unstability in solution, we could not run a 13C NMR spectrum of 5b,
and thus the position of the hydroxyl substituent could not be
ascertained.
(12) (a) McMurry, J . E.; Lectka, T.; Rico, J . G. J . Org. Chem. 1989,
54, 3748-3749. (b) Fu¨rstner, A.; Hupperts, A.; Ptock, A.; J anssen, E.
J . Org. Chem. 1994, 59, 5215-5229.
(13) (a) McMurry, J . E. Chem. Rev. 1989, 89, 1513-1524 and
references cited. (b) Nicolaou, K. C.; Yang, Z.; Liu, J .-J .; Nantermet,
P. G.; Claiborne, C. F.; Renaud, J .; Guy, R. K.; Shibayama, K. J . Am.
Chem. Soc. 1995, 117, 645-652.
(14) Talukdar, S.; Nayak, S. K.; Banerji, A. J . Org. Chem. 1998, 63,
4925-4929 and references cited.

3652 J . Org. Chem., Vol. 64, No. 10, 1999
Gies and Pfeffer
due to the hydroxyl groups is found downfield at 5.42
ppm in CDCl3. Noteworthy in C6D6 the methylene
protons (5.51 and 5.48 ppm) of the dioxomethylene
substituent were found to be diastereotopic due to
hindered rotation around the central bond.17 A complete
assignment of the 13C NMR spectrum of 4b has been
carried out via 13C-1H shift-correlated 2D NMR and 13C-
1H multiple bond correlation.
tion allows a new insight in the application and the
knowledge of the reaction progress.
Exp er im en ta l Section
Gen er a l. All reactions were performed in a dry N2 atmo-
sphere using the Schlenk tube technique. Solutions were
transferred by means of oven-dried syringes or cannula
through rubber septa. Piperonal, vanillin, 2-bromobenzalde-
hyde, and 3-methoxybenzaldehyde are commercial reagents
and were used without further purifications. 2-Iodopiperonal
cyclohexylimine was obtained from piperonal cyclohexylimine
according to a known procedure10b as were the other imines
in this study. 6-Bromovanillin was prepared from O-acetyl-
vanillin20a by bromination in acetic acid20b (HOAc). TiCl3‚DME3/2
and Zn(Cu) were prepared according to the literature.12a
Anhydrous diethyl ether (Et2O), tetrahydrofuran (THF), and
dimethoxyethane (DME) were obtained from distillation on
sodium/benzophenone. Anhydrous alcohol (EtOH) was ob-
1
tained from distillation on sodium ethoxide. H NMR and 13C
NMR experiments were performed at 300 and 75 MHz,
respectively, except for those of 4b which were run at 500 MHz
(1H nucleus) and 125 MHz (13C nucleus) and for those of 5b
whose 1H NMR spectrum was performed at 200 MHz (1H
nucleus). The chemical shifts, δ, are given in ppm related to
TMS, and spectra are measured in CDCl3. The carbons were
identified through a Dept 135 experience. Microanalysis and
mass spectra were performed by the Service Commun de
Microanalise and the Laboratoire de Spectrome´trie de Masse
de Strasbourg. Spectroscopic data for 1a ,10b 2a ,8 and 2-iodo-
piperonal cyclohexylimine10b are in agreement with those of
the literature.
(2)
Such a result would appear to be unprecedented in the
literature dealing with LVT condensations, but it does
not necessarily distinguish this phenanthrene synthesis
from a standard McMurry reaction. Indeed, a recent
2-Br om o-5-m eth oxyben za ld eh yd e.4e To a suspension of
3-methoxybenzaldehyde (3.2 g, 23.4 mmol) in glacial HOAc (80
mL) was slowly added a solution of Br2 (27.2 mmol, 1.4 mL)
in HOAc (10 mL), and the reaction mixture was stirred at room
temperature for 36 h. Upon addition of water (50 mL) a white
suspension was formed, which was filtered and dried under
vacuum. This white powder was then purified by sublimation
(60 °C, 0.5 mmHg), leaving pearly crystals (3.9 g, 78%). 1H
NMR (200 MHz): 10.32 (s, 1H), 7.53 (d, J ) 8.8 Hz, 1H), 7.42
(d, J ) 3.2 Hz, 1H), 7.04 (dd, J ) 8.8, 3.2 Hz, 1H), 3.85 (s,
3H).
investigation18 of the mechanism, when TiCl3‚DME3/2
/
Zn(Cu) was used in the condensation, has shown, inter
alia, that the reflux time exerted an influence on the
amount of olefin formed in the deoxygenation step. We
reached the same conclusion noting that longer reflux
times (ca. 40 h) for the condensation of 2b led to increased
yield of 3b. In this latter case no 5b could be detected
whereas the amount of 4b remained unchanged. The
formation of this side product did not adversely affect our
strategy as this compound can be separated from 3b.
Despite the differences noted above, we felt that the
reaction pathway of our reaction could follow the mech-
anism proposed by Bogdanovic and Bolte.18 A rational
explanation for the formation of 5b would imply the
reaction of a pinacol intermediate with the acidic TiCl3
present as shown in the eq 3, the formation of 4b
resulting from the oxidation of 5b.19
4-Ben zyloxy-5-m eth oxy-2-br om oben za ld eh yd e.21 To a
solution of 4-hydroxy-5-methoxy-2-bromobenzaldehyde (4.0 g,
17.3 mmol) in anhydrous EtOH (25 mL) were added benzyl
chloride (2.6 g, 21 mmol) and K2CO3 (1.4 g, 10.4 mmol). The
resulting suspension was refluxed for 18 h, cooled to room
temperature, diluted with water, and extracted with ethyl
acetate. The bright yellow organic layer was washed with
brine, dried on MgSO4, and filtered, and the solvent was
removed in a vacuum, yielding yellow crystals (4.4 g, 79%)
which were transformed into the corresponding imine without
further purification. 1H NMR: 10.16 (s, 1H), 7.44 (s, 1H), 7.44-
7.33 (m, 5H), 7.09 (s, 1H), 5.18 (s, 2H), 3.89 (s, 3H).
2-Br om oben za ld eh yd e cycloh exylim in e (1b): 89% in
white crystals (n-hexane). H NMR: 8.65 (s, 1H), 8.00 (dd, J
(3)
1
) 7.7, 1.9 Hz, 1H), 7.54 (dd, J ) 7.9, 1.3 Hz, 1H), 7.31 (dd, J
) 7.5, 7.4 Hz, 1H), 7.22 (ddd, J ) 7.6, 7.6, 1.9 Hz, 1H), 3.33-
3.24 (m, 1H), 1.87-1.12 (m, 10H).
2-Br om o-5-m eth oxyben zaldeh yde cycloh exylim in e (1c):
1
76% off-white crystals (methanol). H NMR (200 MHz): 8.61
The process described in this paper, grouping Ullmann
and McMurry reactions, consists of an original and
unprecedented route to oxygenated phenanthrenes. Fur-
thermore, it is likely to be amenable to many different
substituted phenanthrenes starting from cheap com-
mercially and readily available chemicals. Alternatively,
the use of aromatic substrates in the McMurry condensa-
(s, 1H), 7.55 (d, J ) 3.1 Hz, 1H), 7.42 (d, J ) 8.8 Hz, 1H), 6.83
(dd, J ) 8.8, 3.3 Hz, 1H), 3.83 (s, 3H), 3.34-3.24 (m, 1H), 1.87-
1.22 (m, 10H).
4-Ben zyloxy-5-m eth oxy-2-br om oben za ld eh yd e cyclo-
h exylim in e (1d ): quantitative yield of white crystals (hot
CH2Cl2).1H NMR: 8.54 (s, 1H), 7.57 (s, 1H), 7.45-7.32 (m, 5H),
7.04 (s, 1H), 5.14 (s, 2H), 3.93 (s, 3H), 3.30-3.21 (m, 1H), 1.87-
1.20 (m, 10H).
(17) Pfeffer, M.; Sutter, J . P.; Rotteveel, M.; De Cian, A.; Fischer, J .
Tetrahedron 1992, 48, 2427-2432.
(20) (a) Illi, V. O. Tetrahedron lett. 1979, 26, 2431-2432. (b) Raiford,
L. C.; Stoesser, W. C. J . Am. Chem. Soc. 1927, 49, 1077-1080.
(21) Graf, E.; Hosseini, M. W.; Ruppert, R. Tetrahedron lett. 1994,
35, 7779-7782.
(18) Bogdanovic, B.; Bolte, A. J . Organomet. Chem. 1995, 502, 109-
121.
(19) We thank one of the reviewers for this suggestion.

Synthesis of Oxygenated Phenanthrenes
J . Org. Chem., Vol. 64, No. 10, 1999 3653
4,5:4′,5′-Bis(m et h ylen ed ioxy)-6,6′-b ip h en yl-1,1′-d ica r -
boxa ld eh yd e (2a ). This compound was obtained according
to the literature,10a with the following improvements: the
piperonal 1a was reacted with n-BuLi during 50 min, leading
to quantitative metalation. Subsequently, the transmetalation
sequence to the copper complex was extended to 45 min, also
resulting in a better yield for the bisbenzaldehyde 2a : 58% of
ivory crystals (hot CH2Cl2). 1H NMR: 9.75 (s, 2H), 7.64 (d, 2H),
7.01 (d, 2H), 6.06 (d, 2H), 6.04 (d, 2H). 13C NMR: 189.3 (CHO),
152.0, 146.5, 128.8, 114.8 (quaternary C), 127.1, 108.7 (CH),
102.3 (CH2).
the reflux time. An alternative catalytic path22 was tried that
only led to an untractable mixture likely to comprise the
phenanthrene.
3,4:5,6-Bis(m eth ylen edioxy)ph en an th r en e (3a). A flame-
dried two necked 500-mL round-bottomed flask was charged
with TiCl3‚DME3/2 (6.6 g, 23 mmol) and Zn(Cu) (5.2 g, 80 mmol)
under a nitrogen atmosphere, and dry DME (250 mL) was
added. The slurry was heated to reflux for ca. 5 h under a weak
flow of N2 and appeared as a deep purple mixture. A solution
of 2a (0.833 g, 2.8 mmol) in DME (50 mL) was then added
over 3 h by means of a syringe pump. The reaction mixture
turned black. After 20 h of reflux, the residual solids were
removed by filtering twice over a pad of Celite and the solvent
was partialy removed under reduced pressure. The pad was
washed with Et2O, giving rise to a yellow-brown solution. The
combined organic washes were subjected to silica chromatog-
raphy (acetone:n-hexane, 40:60), affording 0.336 g of beige
crystals (45%) which were recrystallized from boiling MeOH.
1H NMR: 7.39 (s, 2H), 7.35 (d, J ) 8.2 Hz, 2H), 7.19 (d, J )
8.2 Hz, 2H), 6.16 (s, 4H). 13C NMR: 145.8,143.0, 128.9, 112.5
(quaternary C), 125.1, 122.1, 109.4 (CH), 100.5 (CH2). Anal.
Calcd for C16H10O4: C, 72.18; H, 3.79. Found: C, 72.22; H,
4.13. MS (EI) m/z: calcd 266.3, found 266.1 (M+).
4,5-(Meth ylen ed ioxy)-6,6′-bip h en yl-1,1′-d ica r boxa ld e-
h yd e (2b). To a solution of 1b (1.0 g, 3.6 mmol) in dry THF
(100 mL) at - 78 °C was added n-BuLi (2.5 mL of 1.6 M in
hexanes, 1.1 equiv), forming a deep orange solution. After the
mixture was stirred for 15-20 min, CuI‚P(OEt)3 (2 g, 5.4
mmol, 1.5 equiv) was added in one portion and the solution
was stirred for 30-45 min. The resulting deep red solution
was treated with 1e (1.3 g, 3.6 mmol). The bright orange
suspension was allowed to warm slowly to room temperature
over a 2-3 h period of time and stirred for an additional 15 h.
The reaction mixture was diluted with CH2Cl2 (100 mL) and
15% aqueous HOAc (60 mL) and stirred vigorously for 15 h.
The yellow solution was transferred to a 1-L separatory funnel,
and the layers were separated. The organic layer was dried
(MgSO4), filtered, and washed with 10% aqueous HCl (3 × 100
mL) and a saturated aqueous Na2CO3 solution (4 × 50 mL)
until the disappearance of the intense blue color of the solution.
The organic layer was finally washed with brine (2 × 50 mL)
and dried over MgSO4, filtered, and concentrated to provide
after crystallization in CH2Cl2 0.58 g (64%) of 2b as pearly
3,4-(Met h ylen ed ioxy)p h en a n t h r en e (3b ). In
a dry
Schlenck tube equipped with a magnetic stirrer, 2b (0.5 g, 1.97
mmol), TiCl3‚DME3/2 (4.67 g, 0.016 mol, 8 equiv), and Zn(Cu)
(4.0 g, 0.060 mol, 30 equiv) in dry DME (30 mL) were heated
to reflux for 40 h under a weak flow of nitrogen. The black
slurry was then cooled to room temperature and carefully
filtered over a pad of Celite to leave a light yellow solution.
The pad was washed twice with CH2Cl2. The solvent was
removed under reduced pressure, leaving a light brown solid
which in chloroform separated into a purple gel and a light
yellow solution. Both the fractions were analyzed by TLC (CH2-
Cl2:n-hexane, 50:50) and revealed the presence of 3b (Rf )
0.60) with a more polar compound (Rf ) 0.10). Flash chro-
matographic separation (acetone:n-hexane, 2:98; acetone was
the only solvent found to solubilize the purple residue) afforded
0.3 g of a very thick colorless oil from which the desired
phenanthrene was crystallized in hot EtOH, affording 3b as
white crystals (0.25 g, 57%). A bright yellow highly polar
fraction was then eluted with 100% acetone and was found to
be the side product 4b (yellow powder, 0.05 g (10%), turns
green in solution). Under the above conditions, no trace of 5b
was found. However, starting with the same amount of
reagents but after only 19 h reflux, elution of the crude mixture
(Et2O:n-hexane, 30:70) gave rise to 3b (19%, Rf ) 0.77), 4b
(10%, Rf ) 0.38), and 5b (8%, Rf ) 0.21).
1
5
crystals. H NMR (1H-1H COSY): 9.93 (d, J
) 0.6
CHO(1′)-H3′
Hz, CHO(1′)), 9.70 (d, 5J CHO(1)-H3 ) 0.6 Hz, CHO(1)), 8.07 (ddd,
3J H2′-H3′ ) 7.7 Hz, J H2′-H4′ ) 1.6 Hz, J H2′-H5′ ) 0.5 Hz, H2′),
4
5
3
4
7.69 (td, J
) 7.4 Hz, J
) 1.3 Hz, H4′), 7.67 (d,
H4′-H3′,5′
H4′-H2′
3J H2-H3 ) 8.2 Hz, H2), 7.60 (tdd, 3J H3′-H4′,2′ ) 7.6 Hz, 4J
H3′-H5′
) 1.4 Hz, 5J H3′-CHO(1′) ) 0.6 Hz, H3′), 7.36 (ddd, 3J H5′-H4′ ) 7.5
Hz, 4J
) 1.4 Hz, J H5′-H2′ ) 0.5 Hz, H5′), 7.01 (dd, 3J
5
H5′-H3′
) 8.0 Hz, 5J H3-CHO(1) ) 0.6 Hz, H3), 6.04 (d, J ) 1.1 Hz,
2
H3-H2
1H, OCH2O), 6.02 (d, 2J ) 1.2 Hz, 1H, OCH2O).13C NMR:
190.9, 189.2 (CHO), 151.7, 146.4, 134.7, 134.2, 129.2, 121.2
(quaternary C), 133.6, 132.0, 129.0, 128.6, 126.7, 108.5 (CH),
102.4 (CH2). Anal. Calcd for C15H10O4: C, 70.86; H, 3.96.
Found: C, 71.43; H, 4.08.
3′-Meth oxy-4,5-(m eth ylen ed ioxy)-6,6′-bip h en yl-1,1′-d i-
ca r boxa ld eh yd e (2c): 70% of white crystals (CH2Cl2 twice).
1H NMR: 9.86 (s, 1H), 9.70 (d, J ) 0.5 Hz, 1H), 7.66 (d, J )
8.2 Hz, 1H), 7.55 (d, J ) 2.6 Hz, 1H), 7.27 (dd, J ) 8.5, 0.5 Hz,
1H), 7.22 (dd, J ) 8.5, 2.6 Hz, 1H), 6.99 (d, J ) 8.0 Hz, 1H),
6.04 (d, J ) 1.0 Hz, 1H), 6.02 (d, J ) 1.1 Hz, 1H), 3.91 (s, 3H).
13C NMR: 190.6, 189.3 (CHO), 160.1, 151.6, 146.5, 135.3,
129.6, 127.1, 121.3 (quaternary C), 133.2, 123.7, 120.9, 111.4
108.5 (CH), 102.2 (CH2), 55.6 (CH3). Anal. Calcd for C16H12O5:
C, 67.60; H, 4.26. Found: C, 67.02; H, 4.36.
1
3b. H NMR: 9.06 (dd, J ) 8.5, 2.0 Hz, 1H), 7.86-7.82 (m,
1H), 7.64 (d, J ) 9.0 Hz, 1H), 7.63-7.58 (m, 2H), 7.55 (d, J )
9.0 Hz, 1H), 7.44 (d, J ) 8.5 Hz, 1H), 7.22 (d, J ) 8.2 Hz, 1H),
6.26 (s, 2H). 13C NMR: 145.4, 143.3, 132.3, 128.5, 128.2, 116.6
(quaternary C), 127.8, 127.2, 127.0, 126.7, 126.2, 124.9, 122.0,
109.0 (CH), 101.2 (CH2). Anal. Calcd for C15H10O2: C, 81.07;
H, 4.54. Found: C, 81.14; H, 4.96.
Bis(3,4-(m eth ylen ed ioxy)-9(10)-p h en a n th r en ol) (4b).
1H NMR: 9.20 (dd, J ) 8.0, 1.1 Hz, 1H), 8.41 (dd, J ) 7.8, 1.4
Hz, 1H), 7.81-7.69 (m, 2H), 6.97 (d, J ) 8.5 Hz, 1H), 6.83 (d,
J ) 8.5 Hz, 1H), 6.28 (s, 2H), 5.41 (broad s, OH). 13C NMR:
147.8 (C9), 144.5 (C3), 144.0 (C4), 129.9 (C5′), 128.0 (C5), 127.4
(C10′), 127.2 (C6), 127.0 (C7), 125.2 (C8′), 122.9 (C8), 118.4
(C1 or C2), 113.8 (C4′), 109.8 (C1 or C2), 107.5 (C10), 101.4
(CH2). MS (EI) m/z: calcd for C30H18O6 474.5, found 474.3 (M+).
3,4-(Met h ylen ed ioxy)-9-(10)p h en a n t h r en ol (5b ). 1H
NMR: 9.09-9.03 (m, 1H), 8.28-8.23 (m, 1H), 7.70-7.61 (m,
2H), 7.24 (d, J ) 8.3 Hz, 1H), 7.16 (d, J ) 8.3 Hz, 1H), 6.96 (s,
1H), 6.24 (s, 2H), 5.12 (broad s, OH). MS (EI) m/z: calcd for
4′-Ben zyloxy-3′-m eth oxy-4,5-(m eth ylen ed ioxy)-6,6′-bi-
p h en yl-1,1′-d ica r boxa ld eh yd e (2d ): 44% of light yellow
crystals (CH2Cl2). H NMR: 9.71 (s, 1H), 9.59 (d, J ) 0.5 Hz,
1
1H), 7.63 (d, J ) 8.2 Hz, 1H), 7.57 (s, 1H), 7.40-7.25 (m, 5H),
6.96 (dd, J ) 8.2, 0.5 Hz, 1H), 6.82 (s, 1H), 6.00 (d, J ) 1.0
Hz, 1H), 5.97 (d, J ) 1.3 Hz, 1H), 5.17 (s, 2H), 3.96 (s, 3H).
13C NMR: 189.5, 189.0 (CHO), 152.6, 151.6, 150.0, 146.5,
135.5, 129.6, 129.2, 127.9, 121.1 (quaternary C), 128.6, 128.6,
128.2, 127.3, 127.3, 125.9, 115.6, 109.5, 108.6 (CH), 102.3, 70.9
(CH2); 56.0 (CH3). Anal. Calcd for C23H18O6: C, 70.76; H, 4.65.
Found: C, 70.21; H, 5.31.
McMu r r y Con den sation . The classical McMurry process12a
was employed for the preparation of 3a whereas in the other
cases the so-called “instant method” described by Fu¨rstner and
co-workers12b was preferred. These two routes only differed in
the experimental conditions since in the latter case no reflux
was required to activate the LVT reagent prior to the addition
of the substrate. In our case the yield of phenanthrene was
barely different in the two methodologies depending only on
C
15H10O3 238.2, found 238.0 (M+).
2-Meth oxy-5,6-(m eth ylen ed ioxy)p h en a n th r en e (3c). In
a dry Schlenck tube equipped with a magnetic stirrer, 2c (0.52
g, 0.0018 mol), TiCl3‚DME3/2 (4.70 g, 0.016 mol, 8.9 equiv), and
(22) Fu¨rstner, A.; Hupperts, A. J . Am. Chem. Soc. 1995, 117, 4468-
4475.

3654 J . Org. Chem., Vol. 64, No. 10, 1999
Gies and Pfeffer
Zn(Cu) (5.1 g, 0.076 mol, 42 equiv) in dry DME (30 mL) were
heated to reflux for 40 h under a weak flow of nitrogen. The
black slurry was cooled to room temperature and carefully
filtered over a pad of Celite to leave a light yellow solution.
The pad was washed twice with CH2Cl2. The solvent was
removed under reduced pressure, spontaneously yielding an
off-white solid (0.25 g, 45%) which was further purified by
preparative TLC on silica with Et2O:n-hexane, 70:30 (Rf )
108.2 (CH), 101.1 (CH2), 55.2 (CH3). Anal. Calcd for C16H12O3:
C, 76.18; H, 4.79. Found: C, 75.56; H, 5.12.
Ack n ow led gm en t. We thank Dr. Roland Graff for
his help in performing and elucidating the 2D NMR
experiments.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra of compounds 2a -d , 3a -c, 4b, and 5b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
0.68). H NMR: 8.95 (d, J ) 9.9 Hz, 1H), 7.62 (d, J ) 8.9 Hz,
1H), 7.48 (d, J ) 8.9 Hz, 1H), 7.42 (d, J ) 8.2 Hz, 1H), 7.26-
7.22 (m, 2H), 7.16 (d, J ) 8.4 Hz, 1H), 6.25 (s, 2H), 3.96 (s,
3H). 13C NMR: 158.1, 145.3, 142.5 (C-O), 133.8, 128.6, 122.3,
116.6 (quaternary C), 128.7, 127.6, 124.5, 122.1, 116.0, 108.4,
J O982522R