Dihydroaromatic boronic esters as building blocks for the synthesis of phenanthrenes and phenanthridines

Article abstract of DOI:10.1002/ejoc.200500025

Alkenyl-substituted dihydroaromatic boronic esters, generated by neutral cobalt(I)-catalysed Diels-Alder reactions, reacted under palladium catalysis conditions with diiodobenzene, bromoiodobenzene and iodoaniline derivatives for the synthesis of regioselectively substituted phenanthrene and phenanthridine derivatives. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200500025

FULL PAPER
Dihydroaromatic Boronic Esters as Building Blocks for the Synthesis of
Phenanthrenes and Phenanthridines
Gerhard Hilt,*[a] Wilfried Hess,[a] and Frank Schmidt[a]
Keywords: Boronic esters / Diazotisation / Heck reaction / Hydroamination / Suzuki coupling
Alkenyl-substituted dihydroaromatic boronic esters, gener-
the synthesis of regioselectively substituted phenanthrene
ated by neutral cobalt( )-catalysed Diels–Alder reactions, re- and phenanthridine derivatives.
I
acted under palladium catalysis conditions with diiodo-
benzene, bromoiodobenzene and iodoaniline derivatives for
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
also be possible through the use of dihydroaromatic boronic
ester 1 as starting material, so 1 was treated with ortho-
dihaloarenes under palladium(0) catalysis conditions. Ac-
cordingly, the dihydroaromatic pinacol boronic esters 1a
and 1b (Scheme 2) and 1,2-diiodobenzene (2) were used in
a domino Suzuki coupling/Heck reaction sequence with
subsequent DDQ oxidation. This procedure gave rise to the
desired compounds 3a and 3b in acceptable nonoptimised
yields, thus verifying our approach in principle.
Introduction
An increasing number of reports describe the use of bo-
ronic esters and their derivatives as nontoxic and easily han-
dled building blocks in organic synthesis.[1,2b] Subsequent
transition metal-catalysed reactions, such as the Suzuki
coupling reaction, generate a wide variety of products in
good yields and with defined regiochemistry.[2] We have re-
ported the successful application of alkynyl boronic esters
as dienophiles in the cobalt(i)-catalysed Diels–Alder reac-
tion for the synthesis of dihydroaromatic boronic esters of
type 1 (Scheme 1). These compounds can be used in Suzuki
coupling reactions for the synthesis of a wide variety of
biaryl, styrene and phenylacetylene derivatives and tricyclic
products.[3] Accordingly, diversity oriented synthetic ap-
proaches[4] for the synthesis of structurally more complex
products from simple starting materials can be envisaged.
By this strategy, the generation of regioselectively substi-
tuted biaryl, phenanthrene and phenanthridine deriva-
tives,[5] which are substructures in biologically active com-
pounds,[6] seems possible.
Scheme 2. Reaction conditions: 1) PdCl2(dppf) 10 mol%, THF, aq.
NaOH, 12 h, room temp. Ǟ 60 °C. 2) DDQ 1.2 equiv., toluene,
room temp., 0.5 h.
Surprisingly, under identical reaction conditions, the cor-
responding aromatic boronic ester 4 gave a 2:1 adduct (iso-
lated in 84% yield), the NMR spectroscopic data of which
suggest the formation of compound 5 (Scheme 3). Product
5 is presumably formed by the expected Suzuki reaction be-
tween 4 and 2 and the insertion of the double bond as ex-
pected in the Heck reaction. The β-hydride elimination nec-
essary for the completion of the Heck reaction of a palla-
dium–phenanthrene species seems to be slower than a sec-
ond Suzuki reaction of a palladium–fluorene species.[7]
Therefore, another molecule of 4 is incorporated and com-
pound 5 is obtained.[8]
Scheme 1.
Results and Discussion
We envisioned that the synthesis of other aromatic com-
pounds such as phenanthrenes and phenanthridines should
[a] Fachbereich Chemie, Philipps-Universität Marburg,
Hans-Meerwein-Straße, 35043 Marburg, Germany
Fax: +49-6421-2825677
E-mail: Hilt@chemie.uni-marburg.de
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200500025
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Building Blocks for the Synthesis of Phenanthrenes and Phenanthridines
FULL PAPER
To circumvent this limitation, we now focused our atten-
tion on an alternative reaction pathway involving iodoani-
line derivatives. Better molecular diversity should be obtain-
able in this approach if the intermediate biarylamine deriva-
tives 10 are used as a synthetic platform. Compounds 10
can be used as a precursors for the synthesis either of phen-
anthrene derivatives (by diazotisation) or of phenanthrid-
ines (by hydroamination). The synthesis of phenanthrenes
involves iodoanilines (9 in Scheme 5), which can easily be
synthesised from the corresponding anilines.[10] The palla-
dium-catalysed coupling reaction proceeds without any dif-
ficulty to deliver the desired biphenylamine products 10,
Scheme 3. Reaction conditions: PdCl2(dppf) 10 mol%, THF, aq.
NaOH, 12 h, room temp. Ǟ 60 °C.
The use of the less reactive dihydroaromatic boronic ester
1a is advantageous, since the Suzuki coupling reaction is
slower and allows the β-hydride elimination of the Heck
intermediate, thus significantly reducing the amount of the
2:1 adduct 5.
A general problem in this synthetic approach to substi-
tuted phenanthrene derivatives is that substituted ortho-di-
iodobenzene derivatives are relatively unstable, not com-
mercially available and quite tedious to synthesise. Besides
these disadvantages, regioselective coupling reactions with
substituted diiodobenzene derivatives such as 1,2-diiodo-4-
methylbenzene seem to be nontrivial to achieve. We there-
fore focused our attention on the use of 1-bromo-2-iodo-
benzene derivative 6, which should allow chemoselective
carbon-carbon bond formations in a domino process. Su-
zuki coupling with the more reactive iodo functionality of
6 should generate 7, and subsequent Heck-type carbon-car-
bon bond formation with the less reactive bromo function-
ality should yield the desired tricyclic compound 8
(Scheme 4).
Scheme 5. Reaction conditions: 1) PdCl2(dppf) 10 mol%, THF, aq.
NaOH, 12 h, room temp. Ǟ 60 °C. 2) DDQ 1.2 equiv., toluene,
room temp., 0.5 h.
Table 1. Suzuki coupling reaction of dihydroaromatic boronic
esters with iodoaniline derivatives.
Scheme 4. Reaction conditions: 1) PdCl2(dppf) 10 mol%, THF, aq.
NaOH, 12 h, room temp. Ǟ 60 °C. 2) DDQ 1.2 equiv., toluene,
room temp., 0.5 h.
While the Suzuki reaction to provide 7 with the Pd(dppf)
catalyst proceeded in good yield,[7] however, the desired
Heck cyclisation to afford the phenanthrene derivative 8 un-
fortunately could not be achieved. Several Pd0 catalysts[9]
tested under standard conditions described in the literature
or even under harsher reaction conditions yielded only
traces of the desired phenanthrene derivative. GCMS analy-
sis shows the reduced product formed by hydrodebromina-
tion (Br Ǟ H in 7) as main product in these cases.
[a] Besides 10e, about 20% of the originally desired dehydrated pro-
duct 2-(2-isopropenyl-5-methylphenyl)-4-methylaniline were also
found. This latter product, however, could not be obtained in ana-
lytically pure form.
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G. Hilt, W. Hess, F. Schmidt
FULL PAPER
which can be isolated in good yields after DDQ oxidation Table 3. Intramolecular hydroamination for the synthesis of phen-
anthridines.
(Table 1).
R1, R2 in biphenylamine
(10)
Product
Yield
The oxidation of the para-toluidine derivative (Table 1;
No. 5) afforded the oxidised product in a single synthetic
step. Besides the desired dehydrogenation of the dihy-
droaromatic ring, the methyl group in a para relationship
to the amine was also oxidised to provide the corresponding
aldehyde functionality, while the other methyl groups pres-
ent in the molecule were untouched.[11]
No.
1
2
3
R1 = CH3
12a
12b
12c
72%
96%
44%
R2 = H
R1 = H
R2 = 5-F
R1 = H
R2 = 5-CH3
Intermediates 10 can be converted into the initially de-
sired phenanthrene derivatives 11 by diazotisation with ni-
trite esters and prolonged heating (3–5 d) in the presence of
borate esters (Scheme 6, Table 2).[12]
In addition to the described synthetic approaches to tri-
cyclic phenanthrene derivatives, we also envisioned dihy-
droaromatic boronic ester 1 as a starting point for another
short synthesis of polycyclic compounds.
Treatment of 1 with 2-iodobenzaldehyde and subsequent
DDQ oxidation provided the biphenyl aldehyde 13
(Scheme 8). Transformation of 13 into the corresponding
nitrone with phenyl hydroxylamine set the stage for an in-
tramolecular 1,3-dipolar cycloaddition (Huisgen reaction).
The nitrone was not isolated but cyclised directly under the
reaction conditions to afford the desired tetracyclic deriva-
tive 14.[15]
Scheme 6. Reaction conditions: tBuONO 2.0 equiv., B(OMe)3
2.0 equiv., toluene, 150 °C, sealed tube, 3–5 d.
Table 2. Synthesis of phenanthrenes by diazotisation of vinyl-sub-
stituted biarylamine compounds.
No.
R in biphenylamine (10)
Product
Yield
1
2
3
H
5-F
4-CO2Me
11a
11b
11c
85%
71%
69%
Scheme 8. Reaction conditions: PhNHOH 3.0 equiv., Et2O, 48 h,
room temp.
Use of BF3·Et2O as a stronger Lewis acid resulted in the
formation of a fluorinated biaryl side product by a Schie-
mann-type reaction.[13]
The synthetic value of the intermediates of type 10 is
exemplified by the use of the aniline derivatives in an intra-
molecular hydroamination reaction for the synthesis of re-
gioselectively substituted phenanthridine derivatives of type
12. This interconversion can easily be accomplished by an
acid-catalysed intramolecular hydroamination of the ole-
finic double bond (Scheme 7, Table 3).[14]
Conclusions
In summary, we have shown that dihydroaromatic alk-
enyl-substituted boronic esters of type 1 can serve as a plat-
form for the synthesis of various classes of polycyclic com-
pounds. The broadest synthetic use was achieved with easily
prepared iodoaniline derivatives, which could be used as
building blocks for the synthesis of a variety of substituted
phenanthrene and phenanthridine derivatives in short reac-
tion sequences.
Experimental Section
General Information: 1H NMR, 13C NMR and 19F NMR: Bruker
ARX 200, ARX 300 or ARX 400 spectrometers. Chemical shifts
for 1H NMR and 13C NMR are reported in ppm relative to tet-
ramethylsilane (TMS, δ = 0.0 ppm) or residual deuterated solvents
as internal standard. Chemical shifts for 19F NMR are reported in
ppm relative to BF3·OEt2 as external standard. GC/MS spectra
were recorded on an Agilent 6890 GC system with an Agilent 5973
Mass Selective Detector. Low resolution and high resolution mass
spectra were recorded on a Varian MAT CH7a, a Finnigan
MAT 95S, a Micromass VG 7070 or a Micromass VG AutoSpec
spectrometer. Thin layer chromatography was performed on pre-
Scheme 7. Reaction conditions: 0.2 equiv. CF3SO3H, toluene, 12 h,
100 °C.
In a control experiment, aniline and α-methylstyrene
were allowed to react under identical reaction conditions,
only trace amounts of the desired hydroamination product
being obtained in this case. However, the corresponding in-
tramolecular reaction produced the phenanthridine deriva-
tives in acceptable to good yields.
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Building Blocks for the Synthesis of Phenanthrenes and Phenanthridines
FULL PAPER
coated sheets obtained from Merck (60, F254). IR spectra were re-
corded on a Bruker IFS Interferometer as KBr pellets. Column
chromatography was performed on Merck silica grade 60 (40–
63 μm, 230–400 mesh). Commercially available chemicals were used
as purchased. Solvents were freshly distilled from drying agents
prior to use.
2×CH2), 4.58–4.72 (m, 2 H, 2×CH) ppm. 13C NMR (50 MHz,
CDCl3): δ = 18.0, 18.4, 21.7, 24.6 (4 C), 36.1, 36.5, 82.8 (2 C),
111.8, 122.3, 123.0, 148.4, 148.6 ppm. The carbon atom beside the
boron atom is not resolved. MS (EI, 70 eV): m/z (%) = 274 (5) [M]
+, 259 (9), 173 (27), 159 (44), 146 (100), 133 (25), 119 (13), 101 (21),
84 (58). HRMS: calcd. for C17H27BO2: 274.2104; found 274.2123.
General Procedure for the Cobalt(I)-Catalysed Diels–Alder Reaction
3,10-Dimethylphenanthrene (3a): This compound was prepared as
described in GP B; dihydroaromatic boronic ester 1a (100 mg,
0.38 mmol) was stirred with 1,2-diiodobenzene (125 mg,
0.38 mmol, 1.0 equiv.) and PdCl2(dppf) (27 mg, 38 μmol, 10 mol%)
in a mixture of THF (4.0 mL) and 10% aqueous NaOH (1.60 mL,
4.0 mmol, 10.5 equiv.) for 12 h. Oxidation of the crude dihydroaro-
matic product was performed with DDQ (104 mg, 0.46 mmol,
1.2 equiv.). Purification by FC (pentane, Rf = 0.23) afforded 3a
(20 mg, 96 μmol, 25%) as a colourless solid, m.p. 60–61 °C.
1H NMR (300 MHz, CDCl3): δ = 2.61 (s, 3 H, CH3), 2.72 (s, 3 H,
CH3), 7.40 (d, J = 8.1 Hz, 1 H, Har), 7.55 (s, 1 H, Har), 7.62–7.66
(m, 2 H, Har), 7.70 (d, J = 8.1 Hz, 2 H, Har), 8.02–8.06 (m, 1 H,
Har), 8.45 (s, 1 H, Har), 8.69–8.74 (1 H, Har) ppm. 13C NMR
(75 MHz, C6D6): δ = 19.9, 22.0, 122.8, 123.4, 125.0, 126.2, 126.6,
127.1, 128.1, 128.5, 130.4, 130.6, 130.8, 131.6, 132.8, 135.5 ppm.
MS (EI, 70 eV): m/z (%) = 206 (100) [M]+, 191 (56), 176 (7), 101 (8),
89 (15), 76 (7). HRMS calcd. for C16H14: 206.1096; found 206.1094.
(GP A): The alkynyl boronate (1.0 equiv.) and the diene (1.0–
2.0 equiv.) were added under argon to a suspension of zinc iodide
(30 mol%), zinc powder (30 mol%) and CoBr2(dppe) (10 mol%)
in anhydrous dichloromethane (2.0–12.0 mL) and the mixture was
stirred for 3 h at room temperature. The solvent was removed under
vacuum, pentane was added, and the mixture was filtered through
a plug of silica. The filtrate was collected and freed from solvent
under vacuum. The crude product was purified by silica gel
chromatography (eluent: MTBE/pentane).
General Procedure for the Palladium(0)-Catalysed Suzuki Cross-
Coupling Reaction (GP B): An oxygen-free solution of tetra-
hydrofuran (4.0–20.0 mL) and aqueous NaOH (10%, 1.6–8.0 mL)
was prepared and the dihydroaromatic boronic ester and the
iodoarene were added, together with PdCl2(dppf) (10 mol%). The
resulting mixture was stirred overnight. Diethyl ether was added,
and the organic phase was separated. The aqueous phase was ex-
tracted twice with diethyl ether. The organic phases were combined
and dried over anhydrous MgSO4, and the solvent was removed
under vacuum. The crude product was purified by silica gel
chromatography (eluent: MTBE/pentane).
2,3,10-Trimethylphenanthrene (3b): This compound was prepared
as described in GP B; dihydroaromatic boronic ester 1b (125 mg,
0.46 mmol) was stirred with 1,2-diiodobenzene (150 mg,
0.46 mmol, 1.0 equiv.) and PdCl2(dppf) (27 mg, 38 μmol, 8 mol%)
in a mixture of THF (4.0 mL) and 10% aqueous NaOH (1.60 mL,
4.0 mmol, 10.5 equiv.) for 12 h. Oxidation of the crude dihydroaro-
matic product was performed with DDQ (124 mg, 0.55 mmol,
1.2 equiv.). Purification by FC (pentane, Rf = 0.21) afforded 3b
(40 mg, 0.18 mmol, 40%) as a colourless solid, m.p. 113–114 °C.
1H NMR (200 MHz, C6D6): δ = 2.30 (s, 3 H, CH3), 2.34 (s, 3 H,
CH3), 2.57 (d, J = 1.0 Hz, 3 H, CH3), 7.42–7.63 (m, 4 H, Har),
7.90–8.02 (m, 1 H, Har), 8.42 (s, 1 H, Har), 8.61–8.71 (m, 1 H,
Har) ppm. 13C NMR (50 MHz, CDCl3): δ = 19.9, 20.0, 20.4, 123.3,
123.4, 125.0, 126.2 (2 C), 126.8, 128.3, 128.8, 130.8, 131.2, 131.5,
General Procedure for the Synthesis of Phenanthrene Derivatives by
Diazotisation (GP C): The biarylamine (1.0 equiv.), tert-butyl ni-
trite (1.5–2.0 equiv.) and trimethylborate (2.0 equiv.) were heated in
toluene (2.5–3.0 mL) in a pressure-stable Pyrex tube at 100–150 °C
for 3–5 d. The solvent was removed under vacuum and the crude
product was purified by silica gel chromatography (eluent: MTBE/
pentane).
2-(2-Isopropenyl-5-methyl-1,4-cyclohexadien-1-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (1a): This compound was prepared as
described in GP A; 4,4,5,5-tetramethyl-2-(3-methylbut-3-en-1-
ynyl)[1,3,2]dioxoborolane (2.00 g, 10.4 mmol), isoprene (1.3 mL,
13 mmol, 1.3 equiv.), CoBr2(dppe) (617 mg, 1.0 mmol, 10 mol%),
zinc powder (195 mg, 3.0 mmol, 30 mol%) and zinc iodide (957 mg,
3.0 mmol, 30 mol%) in CH2Cl2 (12.0 mL) were stirred for 3 h at
room temperature. Purification by FC (MTBE/pentane, 1:99, Rf =
0.41) afforded 1a (2.10 g, 79%) as a colourless liquid. 1H NMR
(200 MHz, CDCl3): δ = 1.23 (s, 12 H, 4×CH3), 1.65 (s, 3 H, CH3),
1.85 (s, 3 H, CH3), 2.58–2.77 (m, 4 H, 2×CH2), 4.71–4.76 (m, 2 H,
CH2), 5.36–5.39 (m, 1 H, CH) ppm. 13C NMR (50 MHz, CDCl3): δ
= 21.7, 22.9, 24.6 (4 C), 30.7, 33.7, 82.9, 111.9, 117.8, 131.0, 147.9,
148.8 ppm. The carbon atom beside the boron atom is not resolved.
MS (EI, 70 eV): m/z (%) = 260 (25) [M]+, 245 (10), 159 (29), 145
(42), 132 (100), 117 (25), 101 (16), 84 (58). HRMS: calcd. for
C16H25BO2: 260.1948; found 260.1939.
132.4, 135.0, 135.8 ppm. IR (KBr): ν = 3080, 3012, 2961, 1604,
˜
1448, 1027, 888, 749 cm–1. MS (EI, 70 eV): m/z (%) = 220 (100)
[M]+, 205 (17). HRMS calcd. for C17H16: 220.1252; found 220.1252.
2-(2-Isopropenyl-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (4): The dihydroaromatic boronic ester 1a (1.29 g,
5.0 mmol) in toluene (20.0 mL) was treated with DDQ (1.32 g,
6.0 mmol, 1.2 equiv.) and stirred for one hour at room temperature.
The reaction mixture was washed twice with an aqueous solution
of 10% NaOH/10% Na2S2O3, the organic phase was dried over
MgSO4, and the solvent was removed under vacuum. Purification
by FC (MTBE/pentane, 1:99, Rf = 0.39) afforded 4 (922 mg,
3.57 mmol, 72%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ
= 1.32 (s, 12 H, 4×CH3), 2.09–2.13 (m, 3 H, CH3), 2.31–2.34 (m,
3 H, CH3), 4.83–4.88 (m, 1 H, =CH2), 5.01–5.05 (m, 1 H, =CH2),
7.09–7.45 (m, 3 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ =
20.9, 24.6, 24.7 (4 C), 83.6 (2 C), 113.8, 127.1, 128.3, 130.6, 134.9,
135.6, 146.8, 147.4 ppm. MS (EI, 70 eV): m/z (%) = 258 (36) [M]+,
200 (15), 185 (10), 175 (39), 158 (100), 142 (87), 131 (23), 115 (22).
HRMS: calcd. for C16H14: 258.1791; found 258.1802.
2-(2-Isopropenyl-4,5-dimethyl-1,4-cyclohexadien-1-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (1b): This compound was prepared as
described in GP A; 4,4,5,5-tetramethyl-2-(3-methylbut-3-en-1-
ynyl)-1,3,2-dioxoborolane (1.00 g, 5.2 mmol), 2,3-dimethyl-1,3-bu-
tadiene (425 mg, 5.2 mmol, 1.0 equiv.), CoBr2(dppe) (309 mg,
0.5 mmol, 10 mol%), zinc powder (98 mg, 1.5 mmol, 30 mol%) and
zinc iodide (478 mg, 1.5 mmol, 30 mol%) in CH2Cl2 (6.0 mL) were
stirred for 3 h at room temperature. Purification by FC (MTBE/
9-(2-Isopropenyl-5-methylbenzyl)-3,9-dimethyl-9H-fluorene (5): This
compound was prepared as described in GP B; dihydroaromatic
boronic ester 4 (98 mg, 0.38 mmol) was stirred with 1,2-diiodo-
pentane 1:99, Rf = 0.40) afforded 1b (767 mg, 54%) as a pale yellow benzene (125 mg, 0.38 mmol, 1.0 equiv.) and PdCl2(dppf) (27 mg,
1
liquid. H NMR (200 MHz, CDCl3): δ = 1.16 (s, 12 H, 4×CH3), 38 μmol, 10 mol%) in a mixture of THF (4.0 mL) and 10% aque-
1.56 (s, 6 H, 2×CH3), 1.81 (s, 3 H, CH3), 2.48–2.72 (m, 4 H, ous NaOH (1.60 mL, 4.0 mmol, 10.5 equiv.) for 12 h. The reaction
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G. Hilt, W. Hess, F. Schmidt
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mixture was extracted with diethyl ether, the organic phase was
dried over MgSO4, and the solvent was removed under vacuum.
Purification by FC (MTBE/pentane, 1:9, Rf = 0.40) afforded 5
(54 mg, 0.16 mmol, 84%) as
(300 MHz, CDCl3): δ = 1.52 (s, 3 H, CH3), 1.72–1.77 (m, 3 H,
2Ј-Isopropenyl-4Ј,5Ј-dimethyl-1,1Ј-biphenyl-2-amine (10b): This
compound was prepared as described in GP B; dihydroaromatic
boronic ester 1b (300 mg, 1.09 mmol) was stirred with 2-iodoaniline
(249 mg, 1.14 mmol, 1.05 equiv.) and PdCl2(dppf) (81 mg,
0.11 mmol, 10 mol%) in a mixture of THF (12.0 mL) and 10%
a
colourless liquid. 1H NMR
CH3), 2.16 (s, 3 H, CH3), 2.41 (s, 3 H, CH3), 3.18 (s, 2 H, CH2), aqueous NaOH (4.8 mL, 12 mmol, 10.5 equiv.) for 12 h. The reac-
4.43–4.49 (m, 1 H, =CH2), 4.97–5.04 (m, 1 H, =CH2), 6.68 (s, 1 H, tion mixture was extracted with diethyl ether, the organic phase
Har), 6.99–6.91 (m, 2 H, Har), 7.02–7.05 (m, 2 H, Har), 7.06–7.34 was filtered through silica gel, and the solvent was removed under
(m, 4 H, Har), 7.48 (s, 1 H, Har), 7.61–7.67 (m, 1 H, Har) ppm. vacuum. The crude product was dissolved in toluene (20 mL) and
13C NMR (75 MHz, CDCl3): δ = 21.0, 21.5, 25.3, 25.9, 41.5, 51.0,
stirred with DDQ (324 mg, 1.4 mmol, 1.2 equiv.) for 2 h. Diethyl
115.4, 119.6, 120.3, 123.6, 123.9, 126.6 (2 C), 126.8, 127.6, 127.7, ether was added, the organic phase was separated, washed twice
131.3, 134.8, 135.0, 136.5, 139.7, 139.8, 141.8, 145.2, 149.2, with an aqueous solution of 10% NaOH/10% Na2S2O3 and dried
152.3 ppm. MS (EI, 70 eV): m/z (%) = 338 (5) [M]+, 323 (6), 193
over MgSO4, and the solvent was removed under vacuum. Purifica-
(100), 178 (34), 145 (25).
tion by FC (MTBE/pentane, 4:1) afforded 10b (187 mg, 0.79 mmol,
72%) as a yellow oil. H NMR (200 MHz, CDCl3): δ = 1.74 (m, 3
1
2-Bromo-2Ј-isopropenyl-4-methoxy-5Ј-methyl-1,1Ј-biphenyl (7): This
compound was prepared as described in GP B; dihydroaromatic
boronic ester 1a (1.27 g, 4.88 mmol) was stirred with 2-bromo-1-
iodo-4-methoxybenzene (1.56 g, 4.98 mmol, 1.0 equiv.) and
PdCl2(dppf) (350 mg, 0.5 mmol, 10 mol%) in a mixture of THF
(10.0 mL) and 10% aqueous NaOH (5.0 mL, 12.5 mmol,
2.5 equiv.) for 36 h. The reaction mixture was extracted with diethyl
ether, the organic phase was dried over MgSO4, and the solvent
was removed under vacuum. The crude product was dissolved in
toluene (40 mL) and stirred with DDQ (1.36 g, 6.0 mmol,
1.2 equiv.) for 2 h. Diethyl ether was added, the organic phase was
separated, washed twice with an aqueous solution of 10% NaOH/
H, CH3), 2.28 (s, 3 H, CH3), 2.31 (s, 3 H, CH3), 3.48 (br.s, 2 H,
NH2), 4.89–4.93 (m, 1 H, =CH2), 4.95–5.00 (m, 1 H, =CH2), 6.69–
6.82 (m, 2 H, Har), 7.00–7.10 (m, 2 H, Har), 7.12–7.18 (m, 2 H,
Har) ppm. 13C NMR (50 MHz, CDCl3): δ = 19.3, 19.4, 23.3, 115.0,
115.2, 118.2, 127.8, 128.1, 130.2, 130.7, 131.8, 134.1, 135.7, 135.8,
141.0, 143.7, 145.9 ppm. IR (KBr): ν = 3469, 3378, 3014, 2968,
˜
2918, 1614, 1485, 1451, 1297, 889, 749 cm–1. MS (EI, 70 eV): m/z
(%) = 237 (6) [M]+, 222 (100), 204 (4), 191 (2), 178 (3), 165 (7), 152
(4). HRMS calcd. for C17H19N: 237.1517; found 237.1515.
5-Fluoro-2Ј-isopropenyl-5Ј-methyl-1,1Ј-biphenyl-2-amine (10c): This
compound was prepared as described in GP B; dihydroaromatic
10% Na2S2O3 and dried over MgSO4, and the solvent was removed boronic ester 1a (100 mg, 0.38 mmol) was stirred with 5-fluoro-2-
under vacuum. Purification by FC (MTBE/pentane, 1:99, Rf iodoaniline (90 mg, 0.38 mmol, 1.0 equiv.) and PdCl2(dppf) (27 mg,
0.10) afforded 7 (1.15 g, 3.61 mmol, 74%) as a yellow oil. 1H NMR 40 μmol, 10 mol%) in a mixture of THF (4.0 mL) and 10% aque-
=
(300 MHz, CDCl3): δ = 1.78 (s, 3 H, CH3), 2.38 (s, 3 H, CH3), 3.83
(s, 3 H, OCH3), 4.81–4.84 (m, 1 H, =CH2), 4.96–4.99 (m, 1 H,
ous NaOH (1.60 mL, 4.0 mmol, 10.5 equiv.) for 12 h. The reaction
mixture was extracted with diethyl ether, the organic phase was
=CH2), 6.86 (dd, J = 8.5, 2.7 Hz, Har), 7.04 (br.s, 1 H, Har), 7.11– filtered through silica gel, and the solvent was removed under vac-
7.28 (m, 4 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0, uum. The crude product was dissolved in toluene (20.0 mL) and
23.5, 55.4, 113.0, 115.7, 117.5, 123.8, 128.1, 128.3, 131.5, 131.9,
stirred with DDQ (104 mg, 0.46 mmol, 1.2 equiv.) for 2 h. Diethyl
135.1, 136.1, 138.4, 140.3, 145.0, 159.0 ppm. MS (EI, 70 eV): m/z ether was added, the organic phase was separated, washed twice
(%) = 316 (1) [M]+, 301 (1), 237 (100), 222 (89), 207 (14), 193 (9),
178 (33), 152 (11), 111 (7). HRMS: calcd. for C16H14: 316.0463;
found 316.0466.
with an aqueous solution of 10% NaOH/10% Na2S2O3 and dried
over MgSO4, and the solvent was removed under vacuum. Purifica-
tion by FC (MTBE/pentane, 4:1) afforded 10c (62 mg, 0.26 mmol,
1
67%) as a yellow solid. H NMR (300 MHz, CDCl3): δ = 1.75 (s,
2Ј-Isopropenyl-5Ј-methyl-1,1Ј-biphenyl-2-amine (10a): This com-
pound was prepared as described in GP B; dihydroaromatic bo-
ronic ester 1a (500 mg, 1.9 mmol) was stirred with 2-iodoaniline
(416 mg, 1.9 mmol, 1.0 equiv.) and PdCl2(dppf) (135 mg,
0.19 mmol, 10 mol%) in a mixture of THF (20.0 mL) and 10%
aqueous NaOH (8.0 mL, 20 mmol, 10.5 equiv.) for 36 h. The reac-
tion mixture was extracted with diethyl ether, the organic phase
was filtered through silica gel, and the solvent was removed under
vacuum. The crude product was dissolved in toluene (20 mL) and
stirred with DDQ (517 mg, 2.28 mmol, 1.2 equiv.) for 2 h. Diethyl
ether was added, the organic phase was separated, washed twice
with an aqueous solution of 10% NaOH/10% Na2S2O3 and dried
over MgSO4, and the solvent was removed under vacuum. Purifica-
3 H, CH3), 2.37 (s, 3 H, CH3), 3.68 (br.s, 2 H, NH2), 4.88–4.93 (m,
1 H, =CH2), 4.97–5.02 (m, 1 H, =CH2), 6.93–6.51 (m, 2 H, Har),
6.96 (dd, J = 8.3, 6.3 Hz, 1 H), 7.04–7.09 (m, 1 H, Har), 7.12–7.19
(m, 2 H, Har), 7.26 (d, J = 7.8 Hz, 1 H, Har) ppm. 13C NMR
(75 MHz, CDCl3): δ = 20.1, 23.2, 101.6 (d, J = 24.3 Hz), 104.6 (d,
J = 21.5 Hz), 115.3, 123.6 (d, J = 2.8 Hz), 128.5, 129.0, 131.4, 131.6
(d, J = 21 Hz), 135.6, 137.1, 140.9, 145.2 (d, J = 10.7 Hz), 146.7,
163.0 (d, J = 243.0 Hz) ppm. IR (KBr): ν = 3479, 3389, 2969, 2920,
˜
1709, 1618, 1508, 974, 827 cm–1. 19F NMR (188 MHz, CDCl3): δ
= –115.4 ppm. MS (EI, 70 eV): m/z (%) = 242 (100) [M + H]+, 228
(78), 211 (34), 198 (23), 185 (19). HRMS (ESI) calcd. for C16H17FN
([M + H]+): 242.1345; found 242.1352.
tion by FC (MTBE/pentane 4:1, Rf = 0.40) afforded 10a (280 mg, Methyl 6-Amino-2Ј-isopropenyl-5Ј-methyl-1,1Ј-biphenyl-3-carboxyl-
1.26 mmol, 66%) as a pale yellow oil. 1H NMR (200 MHz,
ate (10d): This compound was prepared as described in GP B; dihy-
CDCl3): δ = 1.72 (m, 3 H, CH3), 2.35 (s, 3 H, CH3), 3.54 (br.s, 2 droaromatic boronic ester 1a (100 mg, 0.38 mmol) was stirred with
H, NH2), 4.87–4.91 (m, 1 H, =CH2), 4.94–4.98 (m, 1 H, =CH2), methyl 4-amino-3-iodobenzoate (105 mg, 0.38 mmol, 1.0 equiv.)
6.69–6.89 (m, 2 H, Har), 6.99–7.04 (m, 1 H, Har), 7.05–7.17 (m, 3 H,
Har), 7.21–7.27 (m, 1 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ
= 21.0, 23.2, 115.2, 115.3, 118.2, 127.9, 128.2, 128.3, 129.0, 130.6,
and PdCl2(dppf) (27 mg, 40 μmol, 10 mol%) in a mixture of THF
(4.0 mL) and 10% aqueous NaOH (1.60 mL, 4.0 mmol,
10.5 equiv.) for 12 h. The reaction mixture was extracted with di-
ethyl ether, the organic phase was filtered through silica gel, and
131.4, 136.6, 137.1, 140.6, 143.6, 145.9 ppm. IR (KBr): ν = 3470,
˜
3379, 3022, 2968, 2917, 1614, 1483, 1453, 1298, 896, 826, 749 cm–1. the solvent was removed under vacuum. The crude product was
MS (EI, 70 eV): m/z (%) = 223 (18) [M]+, 208 (100), 193 (32), 178
(6), 165 (11), 96 (9). HRMS: calcd. for C16H17N: 223.1361; found 0.46 mmol, 1.2 equiv.) for 2 h. Diethyl ether was added, the organic
dissolved in toluene (20 mL) and stirred with DDQ (104 mg,
223.1355.
phase was separated, washed twice with an aqueous solution of
2530
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 2526–2533

Building Blocks for the Synthesis of Phenanthrenes and Phenanthridines
FULL PAPER
10% NaOH/10% Na2S2O3 and dried over MgSO4, and the solvent
was removed under vacuum. Purification by FC (MTBE/pentane,
2:3, Rf = 0.32) afforded 10d (55 mg, 0.19 mmol, 51%) as a pale
3008, 2916, 1623, 1506, 1479, 1306, 1245, 893, 828, 813 cm–1. MS
(EI, 70 eV): m/z (%) = 237 (40) [M]+, 222 (100) [M – CH3]+, 207
(88), 189 (7), 178 (7), 165 (7), 152 (5), 103 (9). HRMS (EI) calcd.
for C17H19N: 237.1517; found 237.1512.
1
yellow solid. H NMR (200 MHz, CDCl3): δ = 1.75 (s, 3 H, CH3),
2.35 (s, 3 H, CH3), 3.83 (s, 3 H, OCH3), 4.02 (br.s, 2 H, NH2),
4.84–4.89 (m, 1 H, =CH2), 4.93–4.98 (m, 1 H, =CH2), 6.66 (d, J =
8.3 Hz, 1 H, Har), 7.05 (br.s, 1 H, Har), 7.10–7.19 (m, 1 H, Har),
7.22–7.27 (d, J = 8.0 Hz, 1 H, Har), 7.75 (d, J = 8.0 Hz, 1 H, Har),
7.82 (dd, J = 8.2, 2.0 Hz, 1 H, Har) ppm. 13C NMR (50 MHz,
CDCl3): δ = 20.9, 23.4, 51.5, 113.9, 115.5, 119.2, 126.7, 128.6,
128.9, 130.3, 131.3, 132.5, 135.3, 137.2, 140.6, 145.1, 148.2,
3,10-Dimethylphenanthrene (3a/11a): This compound was prepared
as described in GP C; 10a (25 mg, 0.11 mmol), tert-butyl nitrite
(20 μL, 0.17 mmol, 1.5 equiv.) and trimethylborate (24 μL,
0.22 mmol, 2.0 equiv.) were stirred in toluene (3.0 mL) at 100 °C
for 5 d. According to GCMS analysis the desired product was
achieved in quantitative yield. Workup of the reaction afforded 11a
in 85% yield. For detailed work-up procedure and the spectro-
scopic data see under 3a.
167.3 ppm. IR (KBr): ν = 3484, 3382, 2948, 2917, 1699, 1620,
˜
1440 cm–1. MS (EI, 70 eV): m/z (%) = 282 (100) [M + H]+, 268
(49), 251 (30), 236 (42), 224 (52), 208 (41), 194 (44), 180 (19), 167
(23), 152 (11), 128 (11), 115 (14). HRMS calcd. for C18H19NO2:
281.1416; found 281.1397.
3-Fluoro-6,9-dimethylphenanthrene (11b): This compound was pre-
pared as described in GP C; 10c (62 mg, 0.26 mmol), tert-butyl ni-
trite (59 μL, 0.5 mmol, 2.0 equiv.) and trimethylborate (55 μL,
0.5 mmol, 2.0 equiv.) in toluene (2.5 mL) were stirred at 150 °C for
3 d. Purification by FC (MTBE/pentane, 1:4, Rf = 0.30) afforded
11b (41 mg, 0.18 mmol, 71%) as a pale yellow solid, m.p. 61–62 °C.
1H NMR (300 MHz, CDCl3): δ = 2.62 (s, 3 H, CH3), 2.70 (d, J =
1.0 Hz, 3 H, CH3), 7.25–7.50 (m, 4 H, Har), 7.93 (d, J = 8.6 Hz, 1
H, Har), 8.41 (s, 1 H, Har), 8.60 (dd, J = 9.3, 5.6 Hz, 1 H, Har) ppm.
13C NMR (75 MHz, CDCl3): δ = 20.0, 21.9, 111.7 (d, J = 20.3 Hz),
114.4 (d, J = 23.7 Hz), 122.6, 124.7, 124.8, 125.0 (d, J = 3.4 Hz),
126 (d, J = 1.7 Hz) 128.0, 129.5 (d, J = 1.3 Hz), 130.2, 133.5 (d, J
6-Amino-2Ј-isopropenyl-5Ј-methyl-1,1Ј-biphenyl-3-carbaldehyde
(10e): This compound was prepared as described in GP B; dihy-
droaromatic boronic ester 1a (100 mg, 0.38 mmol) was stirred with
2-iodotoluidine (89 mg, 0.38 mmol, 1.0 equiv.) and PdCl2(dppf)
(27 mg, 40 μmol, 10 mol%) in a mixture of THF (4.0 mL) and 10%
aqueous NaOH (1.60 mL, 4.0 mmol, 10.5 equiv.) for 12 h. The re-
action mixture was extracted with diethyl ether, the organic phase
was filtered through silica gel, and the solvent was removed under
vacuum. The crude product was dissolved in toluene (20 mL) and
stirred with DDQ (104 mg, 0.46 mmol, 1.2 equiv.) for 2 h. Diethyl
ether was added, the organic phase was separated, washed twice
with an aqueous solution of 10% NaOH/10% Na2S2O3 and dried
over MgSO4, and the solvent was removed under vacuum. Purifica-
tion by FC (MTBE/pentane, 3:7, Rf = 0.30) afforded 10e (18 mg,
= 8.8 Hz), 133.9, 136.2, 160.8 (J = 245.5 Hz) ppm. IR (KBr): ν =
˜
1619, 1504, 870, 815, 762 cm–1. 19F NMR (188 MHz, CDCl3):
δ = –116.1 ppm. MS (EI, 70 eV): m/z (%) = 224 (100) [M]+, 209
(48), 196 (6), 183 (7), 98 (9). HRMS (ESI) calcd. for C16H13F
([M + H]+): 224.1001; found 224.1007.
Methyl 6,9-Dimethyl-3-phenanthrenecarboxylate (11c): This com-
pound was prepared as described in GP C; 10d (62 mg, 0.22 mmol),
tert-butyl nitrite (59 μL, 0.5 mmol, 2.0 equiv.) and trimethylborate
(55 μL, 0.5 mmol, 2.0 equiv.) in toluene (3.0 mL) were stirred at
150 °C for 3 d. Purification by FC (MTBE/pentane, 1:4) afforded
11c (40 mg, 0.15 mmol, 69%) as a pale yellow solid, m.p. 111–
1
80 μmol, 20%) as a yellow oil. H NMR (300 MHz, CDCl3): δ =
1.75 (s, 3 H, CH3), 2.36 (s, 3H, CH3), 4.20 (br.s, 2 H, NH2), 4.84–
4.89 (m, 1 H, CHH), 4.94–4.99 (m, 1 H, CHH), 6.73 (d, J = 8.5 Hz,
1 H, Har), 6.99–7.40 (m, 3 H, Har), 7.53 (d, J = 2.0 Hz, 2 H, Har),
7.67 (dd, J = 8.3, 2.0 Hz, 1 H, Har) 9.73 (s, 1 H, CHO) ppm.
13C NMR (75 MHz, CDCl3): δ = 20.9, 23.4, 114.3, 115.8, 127.0,
127.3, 128.9, 129.1, 130.6, 131.2, 133.7, 134.8, 137.4, 140.7, 145.0,
1
112 °C. H NMR (300 MHz, CDCl3): δ = 2.64 (s, 3 H, CH3), 2.71
(s, 3 H, CH3), 4.02 (s, 3 H, OCH3), 7.47–7.52 (m, 2 H, Har), 7.79
(d, J = 8.3 Hz, 1 H, Har), 7.94 (d, J = 8.3 Hz, 1 H, Har), 7.14 (dd, J
= 8.3, 1.5 Hz, 1 H, Har), 8.58 (s, 1 H, Har), 9.35 (m, 1 H, Har) ppm.
13C NMR (75 MHz, CDCl3): δ = 20.1, 21.9, 52.2, 123.0, 124.6,
125.0, 125.3, 126.4, 126.8, 127.8, 128.7, 128.8, 130.1, 130.6, 135.1,
149.9, 190.6 ppm. IR (KBr): ν = 3475, 3360, 2918, 1672, 1617,
˜
1614, 825 cm–1. MS (EI, 70 eV): m/z (%) = 251 (21) [M]+, 236 (100),
207 (65), 193 (18), 165 (11), 96 (7), 77 (4). HRMS (ESI) calcd. for
C18H17NO ([M + H]+): 252.1388; found 252.1388.
2-(2-Isopropenyl-5-methylphenyl)-5-methylaniline (10f): This com-
pound was prepared as described in GP B; dihydroaromatic bo-
ronic ester 1a (200 mg, 0.76 mmol) was stirred with 2-iodo-5-meth-
ylaniline (178 mg, 0.76 mmol, 1.0 equiv.) and PdCl2(dppf) (54 mg,
80 μmol, 10 mol%) in a mixture of THF (8.0 mL) and 10% aque-
ous NaOH (3.20 mL, 8.0 mmol, 10.5 equiv.) for 12 h. The reaction
mixture was extracted with diethyl ether, the organic phase was
filtered through silica gel, and the solvent was removed under vac-
uum. The crude product was dissolved in toluene (40 mL) and
stirred with DDQ (204 mg, 0.9 mmol, 1.2 equiv.) for 3 h. Diethyl
ether was added, the organic phase was separated, washed twice
with an aqueous solution of 10% NaOH/10% Na2S2O3 and dried
over MgSO4, and the solvent was removed under vacuum. Purifica-
tion by FC (MTBE/pentane, 1:10) afforded 10f (193 mg,
0.81 mmol, 74%) as a yellow oil. Rf = 0.30 (MTBE/pentane, 1:2).
1H NMR (300 MHz, CDCl3): δ = 7.19 (d, J = 7.8 Hz, 1 H, HAr),
135.5, 136.7, 167.6 ppm. IR (KBr): ν = 2948, 1709, 1616, 1262,
˜
806, 763 cm–1. MS (EI, 70 eV): m/z (%) = 264 (100) [M]+, 233 (56),
202 (16), 189 (41), 116 (12), 101 (14). HRMS (ESI) calcd. for
C18H17O2 ([M + H]+): 265.1229; found 265.1229.
General Procedure for the Synthesis of Phenanthridine Derivatives
(GP D): The (2-isopropenyl-1,1Ј-biphenyl-2Ј-yl)amine was stirred
in a Pyrex tube in toluene with trifluoromethanesulfonic acid at
100 °C for 12 h. After evaporation of the solvent under vacuum the
crude product was purified by chromatography on silica (eluent:
MTBE/pentane).
6,6,8,9-Tetramethyl-5,6-dihydrophenanthridine (12a): This com-
pound was prepared as described in GP D; 10b (50 mg, 0.21 mmol)
and trifluoromethanesulfonic acid (4.0 μL, 45 μmol, 0.2 equiv.)
were stirred in toluene (2.0 mL) at 100 °C for 12 h. After evapora-
tion of the solvent under vacuum, purification by FC (MTBE/pen-
7.09 (dd, J = 7.8, 1.2 Hz, 1 H, HAr), 6.96–6.91 (m, 2 H, HAr), 6.59– tane, 1:4, Rf = 0.48) afforded 12a (36 mg, 0.14 mmol, 72%) as a
6.52 (m, 2 H, HAr), 4.92 (m, 1 H, =CH2), 4.83 (m, 1 H, =CH2), yellow oil. 1H NMR (300 MHz, CDCl3): δ = 1.52 (s, 6 H,
3.36 (br.s, 2 H, NH2), 2.34 (s, 3 H, CH3), 2.04 (s, 3 H, CH3), 1.55
(s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.3, 21.0,
23.3, 112.5, 115.1, 116.6, 127.4, 128.4, 130.8, 131.5, 132.8, 136.2,
C(CH3)2), 2.32 (s, 3 H, CH3), 2.33 (s, 3 H, CH3), 3.76 (br.s, 1 H,
NH), 6.32–7.20 (m, 4 H, Har), 7.55 (s, 1 H, Har), 7.71 (dd, J = 7.8,
1.3 Hz, 1 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.6, 19.7,
29.8 (2 C), 53.3, 115.1, 118.6, 122.9, 123.8, 124.5, 128.2, 129.3,
136.7, 139.3, 140.6, 144.7, 146.3 ppm. IR (film): ν = 3465, 3377,
˜
Eur. J. Org. Chem. 2005, 2526–2533
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2531

G. Hilt, W. Hess, F. Schmidt
FULL PAPER
135.0, 135.7, 138.5, 139.0, 143.3 ppm. IR (KBr): ν = 3357, 1607,
amine (54 mg, 0.5 mmol, 2.0 equiv.) were stirred in diethyl ether
(4.0 mL) at room temperature for 36 h. Another portion of N-
˜
1312, 1262, 872, 746, 726 cm–1. MS (EI, 70 eV): m/z (%) = 237 (7)
[M]+, 222 (100), 204 (5), 165 (7), 103 (7). HRMS: calcd. for phenylhydroxylamine (27 mg, 0.25 mmol, 1.0 equiv.) was added
C17H19N: 237.1517; found 237.1511.
and stirring was continued for 12 h. The solvent was removed un-
der vacuum. Purification by FC (MTBE/pentane, 1:9, Rf = 0.41)
afforded 14 (35 mg, 0.11 mmol, 42%) as a white solid, m.p. 125–
3-Fluoro-6,6,9-trimethyl-5,6-dihydrophenanthridine (12b): This com-
pound was prepared as described in GP D; 10c (78 mg, 0.32 mmol)
and trifluoromethanesulfonic acid (4 μL, 45 μmol, 0.1 equiv.) were
stirred in toluene (2.0 mL) at 100 °C for 12 h. After evaporation of
the solvent under vacuum and purification by FC (MTBE/pentane,
1:10, Rf = 0.36), 12b (75 mg, 0.3 mmol, 94%) was isolated as a
white solid. 1H NMR (300 MHz, CDCl3): δ = 1.60 (s, 6 H,
(CH3)2C), 2.49 (s, 3 H, CH3), 3.83 (br.s, 1 H, NH), 6.48–6.42 (m,
1 H, Har), 6.66–6.56 (m, 1 H, Har), 7.35–7.15 (m, 2 H, Har), 7.59 (m,
1 H, Har), 7.75 (m, 1 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ
= 21.2, 29.8, 53.7, 101.7 (d, J = 24.3 Hz), 105.54 (d, J = 22.0 Hz),
117.5 (d, J = 2.3 Hz), 122.9, 123.3, 124.7 (d, J = 10.2 Hz), 128.0,
129.7, 136.6, 137.3, 144.9 (d, J = 10.7 Hz), 163.4 (d, J =
1
126 °C (decomp.). H NMR (300 MHz, CDCl3): δ = 1.32 (s, 3 H,
CH3), 2.41 (s, 3 H, CH3), 4.11 (s, 1 H, CH), 4.32 (d, J = 7.6 Hz, 1
H, =CH2), 4.67 (d, J = 7.6 Hz, 1 H, =CH2), 6.92–7.09 (m, 4 H,
Har), 7.15–7.26 (m, 4 H, Har), 7.33 (d, J = 8.0 Hz, 1 H, Har), 7.43
(td, J = 7.6, 1.3 Hz, 1 H, Har), 7.75 (br.s, 1 H, Har), 7.91 (d, J =
8.0 Hz, 1 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3, 24.0,
50.0, 76.2, 78.8, 119.0 (2 C), 123.9, 123.9, 124.4, 126.4, 127.3, 128.4
(2 C), 129.2, 129.7, 130.4, 131.4, 131.9, 133.3, 136.4, 136.9,
151.2 ppm. IR (film): ν = 2956, 2918, 1594, 1483, 1449, 1000, 821,
˜
766, 701 cm–1. MS (EI, 70 eV): m/z (%) = 327 (5) [M]+, 206 (100),
192 (33), 178 (7), 165 (6), 93 (11), 77 (5). HRMS calcd. for
C23H21NO: 327.1623; found 327.1629.
245.3 Hz) ppm. IR (KBr): ν = 3362, 2958, 1721, 1618, 1499, 1474,
˜
1450, 1294, 1260, 1154, 1109, 1001, 840, 822, 576 cm–1. MS (EI,
70 eV): m/z (%) = 241 (5) [M]+, 226 (100) [M – CH3]+, 211 (4), 183
(6), 170 (3), 113 (5). HRMS (ESI) calcd. for C16H17FN
([M + H]+): 242.1345; found 242.1317.
Acknowledgments
Financial support from the Deutsche Forschungsgemeinschaft
(DFG) and the Fonds der Chemischen Industrie is gratefully ac-
knowledged.
2,6,6,9-Tetramethyl-5,6-dihydrophenanthridine (12c): This com-
pound was prepared as described in GP D; 10f (37 mg, 0.16 mmol)
and trifluoromethanesulfonic acid (4 μL, 45 μmol, 0.3 equiv.) were
stirred in toluene (2.0 mL) at 100 °C for 12 h. After evaporation of
the solvent under vacuum and purification by FC (MTBE/pentane,
1:25), 12c (16 mg, 70 μmol, 44%) was isolated as a white solid.
1H NMR (300 MHz, CDCl3): δ = 1.59 (s, 6 H, (CH3)2C), 2.42 (s,
3 H, CH3), 2.48 (s, 3 H, CH3), 3.82 (br.s, 1 H, NH), 7.65–6.68 (m,
6 H, Har) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.9, 21.2, 29.4,
53.5, 114.7, 115,5, 123.16, 123.19, 123.7, 128.1, 129.4, 130.0, 136.4,
138.2, 139.0, 140.8 ppm. MS (EI, 70 eV): m/z (%) = 237 (8) [M]+,
222 (100) [M – CH3]+, 165 (7), 111(4), 102 (4). HRMS (ESI) calcd.
for C17H20N ([M + H]+): 238.1595; found 238.1614.
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Schreiber, Angew. Chem. 2004, 116, 49–60; Angew. Chem. Int.
Ed. 2004, 43, 46–58; D. R. Spring, Org. Biomol. Chem. 2003,
1, 3867–3870; S. L. Schreiber, Science 2000, 287, 1964–1969.
[5] V. Mamane, P. Hannen, A. Fürstner, Chem. Eur. J. 2004, 10,
4556–4575, and references cited therein; T. Ishikawa, H. Ishii,
Heterocycles 1999, 50, 627–639; A. J. Floyd, S. F. Dyke, S. E.
Ward, Chem. Rev. 1976, 76, 509–562.
[6] O. Baudoin, F. Gueritte, in: Studies in Natural Products Chem-
istry, 2003, 29 (Bioactive Natural Products, Part J), 355–417; V.
Kumar, Poonam, A. K. Prasad, V. S. Parmar, Nat. Prod. Re-
ports 2003, 20, 565–583; V. Simanek, R. Vespalec, A. Sedo, J.
Ulrichova, J. Vicar, in: NATO Science Series, II: Mathematics,
Physics and Chemistry 2003, 129 (Chemical Probes in Biology),
245–254; J. Dostal, J. Slavik, in: Studies in Natural Products
Chemistry 2002, 27 (Bioactive Natural Products, Part H), 155–
184.
[7] The NMR spectroscopic data suggest the formation of the flu-
orene derivative 5. If a similar intermediate is proposed for
the reactions of 1a or 1b with 2, an equilibrium between an
intermediately formed sp3-bonded palladium fluorene species
and a palladium phenanthrene species must be considered.
While the fast Suzuki coupling of the palladium fluorene inter-
mediate with 4 produced 5, the relatively slow coupling of the
palladium phenanthrene species with 1a or 1b favoured the β-
hydride elimination from a palladium phenanthrene species to
give 3a or 3b.
2Ј-Isopropenyl-5Ј-methyl-1,1Ј-biphenyl-2-carbaldehyde (13): This
compound was prepared as described in GP B; dihydroaromatic
boronic ester 1a (100 mg, 0.38 mmol) was stirred with 2-iodoben-
zaldehyde (88 mg, 0.38 mmol, 1.0 equiv.) and PdCl2(dppf) (27 mg,
40 μmol, 10 mol%) in a mixture of THF (4.0 mL) and 10% aque-
ous NaOH (1.60 mL, 4.4 mmol, 11.4 equiv.) for 12 h. The reaction
mixture was extracted with diethyl ether, the organic phase was
filtered through silica gel, and the solvent was removed under vac-
uum. The crude product was dissolved in toluene (20.0 mL) and
stirred with DDQ (324 mg, 1.4 mmol, 1.2 equiv.) for 2 h. Diethyl
ether was added, the organic phase was separated, washed twice
with an aqueous solution of 10% NaOH/10% Na2S2O3 and dried
over MgSO4, and the solvent was removed under vacuum. Purifica-
tion by FC (MTBE/pentane, 1:9, Rf = 0.49) afforded 13 (65 mg,
1
0.28 mmol, 73%) as a white solid. H NMR (300 MHz, CDCl3): δ
= 1.53 (dd, J = 1.5, 1.0 Hz, 3 H, CH3), 2.38 (s, 3 H, CH3), 4.81–
4.88 (m, 1 H, =CH2), 4.95–5.02 (m, 1 H, =CH2), 7.02–7.08 (m, 1
H, Har), 7.17–7.23 (m, 2 H, Har), 7.33–7.51 (m, 2 H, Har), 7.59 (td,
J = 7.5, 1.5 Hz, 1 H, Har), 7.93–8.02 (m, 1 H, Har) ppm. 13C NMR
(75 MHz, CDCl3): δ = 20.5, 23.0, 113.9, 115.3, 126.6, 126.9, 128.5,
128.7, 130.2, 130.7, 133.2, 134.4, 137.0, 140.3, 144.6, 149.4,
190.1 ppm. IR (film): ν = 3077, 2969, 2920, 2849, 1694, 1598, 900,
˜
825, 775 cm–1. MS (EI, 70 eV): m/z (%) = 236 (3) [M]+, 207 (100),
192 (65), 165 (20), 152 (13). HRMS calcd. for C17H16O: 236.1201;
found 236.1203.
3a,6-Dimethyl-1-phenyl-1,3,3a,11b-tetrahydrophenanthro[9,10-c]iso-
xazole (14): Biaryl 13 (60 mg, 0.25 mmol) and N-phenylhydroxyl-
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Building Blocks for the Synthesis of Phenanthrenes and Phenanthridines
FULL PAPER
[8] H. A. Wegner, L. T. Scott, A. de Meijere, J. Org. Chem. 2003,
68, 883–887; A. de Meijere, P. von Zezschwitz, H. Nuske, B.
Stulgies, J. Organomet. Chem. 2002, 653, 129–140.
[9] Catalyst systems tested were: a) Pd(OAc)2, PPh3, NEt3, b) (o-
TolylPPh2)Pd(OAc) dimer, NaOH, and c) Pd(CH3CN)2Cl2,
Na2CO3, Bu4NBF4. In all cases, even at elevated temperatures,
mostly the reduced hydrodebromination product was detect-
able by GCMS.
[10] Synthesis of iodoaniline derivatives by the adopted procedure:
W.-J. Xiao, H. Alper, J. Org. Chem. 1999, 64, 9646–9652.
[11] B. Lal, R. M. Gidwani, J. Reden, N. J. de Souza, Tetrahedron
Lett. 1984, 25, 2901–2904.
[12] Compare with: D. L. F. de Tar, C.-C. Chu, J. Am. Chem. Soc.
1960, 82, 4969–4974.
[13] C. M. Sharts, J. Chem. Edu. 1968, 45, 185–192.
[14] J. A. Seijas, M. P. Vázquez-Tato, M. M. Martínez, Synlett
2001, 875–877; M. Beller, C. Breindl, Tetrahedron 1998, 54,
6359–6368; T. Rische, P. Eilbracht, Synthesis 1997, 1331–1337.
[15] A. Padwa, K. F. Koehler, Heterocycles 1986, 24, 611–615; A.
Padwa, H. Ku, A. Mazzu, J. Org. Chem. 1978, 43, 381–387.
Received: January 12, 2005
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