Photochemical synthesis of phenanthridines: Exploring fluoro and protected catechol substitution

Article abstract of DOI:10.1002/ejoc.201300218

Substituted phenanthridines, such as the natural product trispheridine, have been accessed by the practical photochemical cyclization of N-benzylanilines. Functionalities, with a focus on fluoro substituents and protected catechols, are well tolerated on both the A and C rings. The phenanthridines were accessed in good to very good yields (up to 95 %) from iodinated substrates, whereas brominated substrates performed poorly in comparison (0-48 %). Substituted phenanthridines, such as the natural product trispheridine, can be accessed by the practical photochemical cyclization of N-benzylanilines, with functionalities tolerated on both the A and C rings. The phenanthridines are accessible in good to very good yields (up to 95 %) from iodinated substrates, whereas brominated substrates perform poorly in comparison (0-48 %). Copyright

Full text of DOI:10.1002/ejoc.201300218

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FULL PAPER
Phenanthridine Synthesis
Substituted phenanthridines, such as the
natural product trispheridine, can be
accessed by the practical photochemical
cyclization of N-benzylanilines, with func-
tionalities tolerated on both the A and C
rings. The phenanthridines are accessible in
good to very good yields (up to 95%) from
iodinated substrates, whereas brominated
substrates perform poorly in comparison
(0–48%).
A. M. Linsenmeier, C. M. Williams,*
S. Bräse* ......................................... 1–11
Photochemical Synthesis of Phenanthrid-
ines: Exploring Fluoro and Protected Cat-
echol Substitution
Keywords: Natural products / Fused hetero-
cycles / Photolysis / Cyclization
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A. M. Linsenmeier, C. M. Williams, S. Bräse
FULL PAPER
DOI: 10.1002/ejoc.201300218
Photochemical Synthesis of Phenanthridines: Exploring Fluoro and Protected
Catechol Substitution
Anna M. Linsenmeier,[a] Craig M. Williams,*[b] and Stefan Bräse*[a]
Keywords: Natural products / Fused heterocycles / Photolysis / Cyclization
Substituted phenanthridines, such as the natural product tris-
tolerated on both the A and C rings. The phenanthridines
pheridine, have been accessed by the practical photochemi- were accessed in good to very good yields (up to 95%) from
cal cyclization of N-benzylanilines. Functionalities, with a fo-
cus on fluoro substituents and protected catechols, are well
iodinated substrates, whereas brominated substrates per-
formed poorly in comparison (0–48%).
Introduction
A large number of natural products contain the phen-
anthridine ring system, ranging from relatively unsubsti-
tuted examples like trispheridine (1)[1,2] through to more
complex natural products such as sanguinarine (2)[3] and
chelerythrine (3; Figure 1).[4] Interest in these alkaloids has
been driven by a broad display of biological activity, for
example, antifungal, antitumor, antibacterial, nematodical,
and cytotoxic activities.[4,5]
Scheme 1. Photochemical conversion of halogenated N-benzylanil-
ines.[6]
Most phenanthridine natural products clearly possess, in
addition to A-ring substituents, substituents on the C ring.
However, most of the photochemical syntheses of phen-
anthridines reported so far only describe the introduction
of different functional groups on the A ring[7] with few re-
ports describing substitution of the C ring.[8]
In this work we investigated the scope and limitations
of our developed photolytic reaction for the synthesis of
phenanthridines by investigating aniline derivatives contain-
ing electron-deficient or -rich substituents on the C-ring
precursor (Figure 2). In particular, the focus of this study
was the novel introduction of fluorine atoms as molecules
containing this atom play a major role in modern pharma-
ceutical and agrochemical research in the prevention of
various biological metabolisms.[9] We also investigated the
dioxolane ring system because this opens access to the me-
tabolite-active catechol functional group. Lastly, we wanted
to explore the impact of the iodine atom on the cyclization
and whether substitution of that atom for bromine would
be possible to increase the scope of this method.
Figure 1. Examples of phenanthridine natural products.
Recently we reported a rapid, convenient, and practical
photolytic access to a variety of phenanthridine derivatives
in very good yields, with functionalities mainly located on
the A ring (Scheme 1).[6]
[a] Institute of Organic Chemistry, Karlsruhe Institute of
Technology (KIT),
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49-721-6084-8581
E-mail: Braese@kit.edu
Homepage: http://www.ioc.kit.edu/braese/
[b] School of Chemistry and Molecular Bioscience, University of
Queensland,
Brisbane 4072, Queensland, Australia
Fax: +61-7-3365-4299
E-mail: c.williams3@uq.edu.au
Homepage: http://scmb.uq.edu.au/staff/craig-williams
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300218.
Figure 2. C-ring substitution.
2
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Photochemical Synthesis of Phenanthridines
Table 1. N-Alkylation (e.g., 11) and subsequent photolysis cycliza-
tion products (e.g., 12).
Results and Discussion
Initially we prepared a variety of iodides (i.e., 11a) and
bromides (i.e., 11b) with meta-fluoro substitution of the C-
ring precursor. For the N-alkylation we used in both cases
the method of Romera et al.,[10] which gave rapid and easy
access to all alkylated anilines of type 11, in which numer-
ous functionalities are accommodated (halogens, free OH,
ester, CF3, and nitro groups).
Thus, excess of the corresponding aniline (9) was intro-
duced into the reaction vial together with the benzyl brom-
ide 10 and a catalytic amount of potassium iodide in aceto-
nitrile. The vial was sealed and the mixture then heated for
15 min in a microwave reactor at 170 °C to give the desired
products of type 11 in yields of 63–97% (Table 1, entries 1–
8). The alkylated anilines were irradiated at 254 nm in anhy-
drous acetonitrile in a Rayonet photochemical reactor to
give phenanthridine derivatives of type 12.
First, we investigated the iodinated derivatives and iso-
lated the cyclization products 21a–28a in yields of 46–95%
(Table 1, entries 1–8). The trifluoromethyl and phenyl deriv-
atives 25 and 26 were obtained in yields of 95% whereas
the ester 22, the chloride 24, and the nitro compound 27
were isolated in yields of 60, 79, and 64%, respectively. The
yields were generally lower in these cases than those ob-
tained for the products with an unsubstituted C ring (gen-
erally 95%).[6] In particular, in the case of the hydroxy de-
rivative 23, the fluorine atom on the C ring lowered the
yield significantly from 90 to 46%.
In the next phase of this study we investigated whether
it was possible to exchange the iodine atom for a bromine
atom. The overall results were generally disappointing as
bromide retarded the photochemical cyclization consider-
ably with the best yields (27 and 24%) obtained for deriva-
tives 21 and 24 (Table 1, entries 1 and 4). Complete decom-
position was observed with the alkylated anilines 14 and 15
(Table 1, entries 2 and 3). Compounds 25 and 26, which
were obtained from the iodinated aniline derivatives in
yields of 95%, were obtained in yields of only 17 and 11%,
respectively, from the bromide derivatives. After 2 h reac-
tion time, in all cases no starting material could be re-iso-
lated and no alternative products were identified. Shorter
reaction times led to mixtures of starting material and prod-
uct, or decomposed starting material.
The reactions of the nitro compounds 19b and 30 like-
wise did not give rise to cyclized material. Instead, scission
of the N–CH2 bond was observed in preference and the
anilines 29 and 31 were isolated (Scheme 2). Although this
was unusual, such photochemical deprotection of nitro-sub-
stituted systems has been observed in the case of carb-
amates.[11]
The fluoro substituent was then replaced by the dioxol-
ane ring system; five bromide derivatives with varying func-
To confirm whether the position of the fluoro substituent tionalities on the A ring were synthesized (Table 3). The N-
had a direct influence on the reactions of the bromides, two alkylated products were obtained in good-to-excellent
anilines with para-fluoro substitution of the C-ring precur- yields, as has been the trend throughout the whole study.
sor, 35 and 36 (Table 2, entries 1 and 2), were synthesized. However, bromides 43 and 44 delivered the corresponding
In this case, the results of the photolysis were similar to photolysis products 46 and 47 in yields of only 16 and 17%,
those above with only the unsubstituted cyclized product 37 respectively (Table 3, entries 3 and 4), matching the per-
being obtained (24% yield).
formance seen in the bromide series above. The phenyl de-
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A. M. Linsenmeier, C. M. Williams, S. Bräse
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Table 3. N-Alkylation (e.g., 39) and subsequent photolysis cycliza-
tion products (e.g., 40).
Scheme 2. Scission of the N–CH2 bond in the N-alkylated com-
pounds 19b and 30.
Table 2. N-Alkylation (e.g., 33) and subsequent photolysis cycliza-
tion products (e.g. 34).
rivative 48 was only obtained in trace amounts (Table 3,
entry 5).
Photolysis of the first derivative in this series, 41b, led to
the natural product trispheridine (1) in 48% yield (Table 3,
entry 1). However, when the iodinated derivative 41a was
irradiated, the natural product was isolated in 82% yield. In
comparison with the best synthesis of this natural product
reported so far, our procedure provides an improvement in
yield of 58–75%[12] and a vastly improved atom economy.
Scheme 3. Proposed mechanism.
Beyond the synthetic chemist’s general rule of thumb that
Ar–I substrates outperform Ar–Br, it is not apparent as to
Mechanistically, the study herein offers no contradiction why the brominated substrates perform considerably worse
to that proposed in our communication,[6] that is, the pro- than the iodinated substrates in this system. Comparison of
cess follows a classical photochemical radical cleavage of the UV spectra of the starting materials (Br and I) showed
the C–I bond (i.e., 49) to generate 50, which then undergoes similar absorption properties with maxima at around
cyclization and subsequent ejection of a hydrogen atom 250 nm, which suggests they absorb similar amounts of
(i.e., 51) to afford the dehydrophenanthridine 52. It is pos- light. A survey of the literature covering related systems
sible that the hydrogen atom resulting from 51 could propa- show that yield outcome is very substrate-dependent, irre-
gate the reaction in starting material 49. Finally, oxidation spective of the halogen.[13] In other cases, aryl bromides
with iodine or bromine (arising from hydrogen iodide/ were simply ignored and the focus concentrated entirely on
bromide), or aerial oxidation on work up, provides the aryl iodides.[14] Perhaps this tendency arises from the
product (i.e., 52; Scheme 3).
knowledge that aryl iodides have excited states (e.g., nσ* or
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Photochemical Synthesis of Phenanthridines
sσ*) not available to aryl bromides or chlorides.[15] Lastly,
it is also possible that iodides deliver better results because
the stronger oxidation potential of bromine in comparison
with iodine may lead to decomposition of the starting mate-
rial and/or product.
Then the solution was dried (MgSO4) and the solvent evaporated.
The crude product was purified by flash chromatography.
N-(2-Iodo-4-fluorobenzyl)aniline (13a): The crude product was puri-
fied by flash chromatography (cyclohexane/EtOAc = 5:1) and the
product obtained as a colorless oil in 92% (120 mg, 0.367 mmol)
yield. Rf = 0.47 (Cy-Hex/EtOAc = 5:1). 1H NMR (CDCl3,
300 MHz): δ = 7.59 (dd, J = 7.9, 2.3 Hz, 1 H), 7.34 (dd, J = 8.5,
6.0 Hz, 1 H), 7.18 (t, J = 7.8 Hz, 2 H), 7.03 (dt, J = 8.3, 2.5 Hz, 1
H), 6.74 (t, J = 7.3 Hz, 1 H), 6.59 (d, J = 7.9 Hz, 2 H), 4.29 (s, 2
H), 4.22 (br. s, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.2
(d, J = 250.6 Hz), 147.3, 136.7 (d, J = 3.0 Hz), 129.3, 129.3 (2 CH),
126.2 (d, J = 23.8 Hz), 117.9, 115.3 (d, J = 20.7 Hz), 112.9 (2 CH),
Conclusions
A range of fluoro and catechol-protected (dioxolane)
substituted phenanthridine derivatives have been synthe-
sized in yields of 46–95%. We have shown that functionali-
zation of both the A and C rings is tolerated. Unfortunately,
substitution of the iodine atom by a bromine atom led to
poor yields of cyclized products with less tolerance of func-
tional groups. Finally, we have significantly improved the
efficiency and yield of the total synthesis of the natural
product trispheridine in comparison with previously re-
ported strategies.
97.3 (d, J = 8.1 Hz), 52.3 ppm. IR (film on KBr): ν = 3419 (m),
˜
3052 (w), 3020 (vw), 2918 (vw), 1920 (vw), 1603 (m), 1582 (m),
1506 (m), 1475 (m), 1430 (w) cm–1. UV/Vis (CH3CN): λmax (A) =
231 (1.1), 243 (1.0) nm. MS (EI): m/z (%) = 327 (100) [M]+, 234
(59), 198 (25). HRMS (EI): calcd. for C13H11NFI 326.9920 [M]+;
found 326.9919.
Methyl 2-(2-Iodo-4-fluorobenzylamino)benzoic Acid (14a): The
crude product was purified by flash chromatography (cyclohexane/
EtOAc = 10:1) and the product obtained as a yellow solid in 69%
(106 mg, 0.275 mmol) yield. Rf = 0.43 (Cy-Hex/EtOAc = 10:1),
m.p. 117–118 °C. 1H NMR (CDCl3, 400 MHz): δ = 8.29 (t, J =
5.9 Hz, 1 H), 7.93 (dd, J = 8.0, 1.6 Hz, 1 H), 7.58 (dd, J = 7.9,
2.6 Hz, 1 H), 7.30–7.22 (m, 2 H), 6.99 (dt, J = 8.3, 2.6 Hz, 1 H),
6.64–6.60 (m, 1 H), 6.44 (d, J = 8.5 Hz, 1 H), 4.37 (d, J = 5.9 Hz,
2 H), 3.87 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 169.1,
161.5 (d, J = 250.4 Hz), 150.4, 136.1 (d, J = 3.1 Hz), 134.7, 131.7,
128.8 (d, J = 8.0 Hz), 126.3 (d, J = 24.0 Hz), 115.4 (d, J = 20.7 Hz),
115.4, 111.6, 110.5, 97.2 (d, J = 8.1 Hz), 51.6, 51.3 ppm. IR (ATR):
Experimental Section
All reactions were performed in dried glassware under a positive
pressure of argon unless otherwise stated. All reagents and solvents
were dried, distilled or purified before use according to Chai and
Amarego.[16] Acetonitrile was purchased as extra dry solvent (H2O
Ͻ50 ppm). TLC was performed on E. Merck silica gel 60 F254 pre-
coated plates and column chromatography on silica gel (Flash silica
1
gel 230–400 mesh). H and 13C NMR spectra were recorded with
ν = 3360 (w), 2953 (vw), 1682 (w), 1606 (w), 1578 (m), 1516 (w),
˜
Bruker AV300 (300.13 MHz, 75.47 MHz), AM400 (400.13 MHz,
100.62 MHz), and DRX500 (500.13 MHz, 125.76 MHz) instru-
ments. Coupling constants are given in Hz and chemical shifts are
reported in δ values in ppm with the solvent resonance as the in-
ternal standard (1H NMR: CDCl3: δ = 7.26 ppm, CD3OD: δ =
3.31 ppm; 13C NMR: CDCl3: δ = 77.0 ppm, CD3OD: δ =
49.3 ppm). Data are reported as follows: chemical shift, multiplicity
(s = singlet, br. s = broad singlet, d = doublet, t = triplet, q =
quartet, sept. = septet, dd = double doublet, dt = double triplet,
ddd = double double doublet, m = multiplet), coupling constants
[Hz], and integration. High- and low-resolution electron impact ac-
curate mass spectra (HREIMS) were recorded with a Finnigan
Model MAT 900 spectrometer. Melting points were determined
with a Laboratory Devices Inc. Modell Mel-Temp II or a Stanford
Research System Modell Opti Melt SRS instrument. IR spectra
were recorded with a Bruker Alpha spectrophotometer as thin films
in KBr disks or by the ATR technique (ATR = attenuated total
reflection). Data are reported as followed: vs. = very strong (0–
20% T), s = strong (21–40% T), m = middle (41–60% T), w =
weak (61–80% T), vw = very weak (81–100% T). For microwave-
assisted reactions, the CEM discover microwave was used and for
UV photolysis reactions a Rayonet Photochemical RPR-100 reac-
tor at 254 nm was used.
1472 (w), 1461 (w), 1430 (m) cm–1. UV/Vis (CH3CN): λmax (A) =
256 (0.4), 348 (0.3) nm. MS (EI): m/z (%) = 385 (100) [M]+, 351
(26), 327 (33), 235 (39), 198 (33). HRMS (EI): calcd. for
C15H13IFNO2 384.9975 [M]+; found 384.9973.
3-(2-Iodo-4-fluorobenzylamino)phenol (15a): The crude product was
purified by flash chromatography (cyclohexane/EtOAc = 1:1) and
the product obtained as a yellow oil in 82% (112 mg, 0.327 mmol)
yield. Rf = 0.64 (Cy-Hex/EtOAc = 1:1). 1H NMR (CDCl3,
400 MHz): δ = 7.54 (dd, J = 7.9, 2.3 Hz, 1 H), 7.28–7.23 (m, 1 H),
7.01–6.95 (m, 2 H), 6.18–6.15 (m, 2 H), 6.03–6.02 (m, 1 H), 4.20
(s, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.2 (d, J =
250.8 Hz), 156.5, 149.0, 136.5 (d, J = 3.2 Hz), 130.3, 129.4 (d, J =
8.0 Hz), 126.3 (d, J = 23.8 Hz), 115.3 (d, J = 20.8 Hz), 106.1, 105.0,
99.9, 97.3 (d, J = 8.0 Hz), 52.3 ppm. IR (ATR): ν = 3405 (w), 1581
˜
(s), 1495 (m), 1474 (s) cm–1. UV/Vis (CH3CN): λmax (A) = 245 (0.3),
278 (0.1), 291 (0.1) nm. MS (EI): m/z (%) = 342 (100) [M]+, 234
(75), 216 (40). HRMS (EI): calcd. for C13H11IFNO 342.9869
[M]+; found 342.9866.
N-(2-Iodo-4-fluorobenzyl)-4-chloroaniline (16a): The crude product
was purified by flash chromatography (cyclohexane/EtOAc = 5:1)
and the product obtained as a yellow oil in 77% (110 mg,
0.304 mmol) yield. Rf = 0.37 (Cy-Hex/EtOAc = 5:1). 1H NMR
(CDCl3, 400 MHz): δ = 7.60 (dd, J = 7.9, 2.6 Hz, 1 H), 7.29 (dd,
J = 8.6, 5.9 Hz, 1 H), 7.14–7.10 (m, 2 H), 7.03 (dt, J = 8.4, 2.6 Hz,
1 H), 6.52–6.48 (m, 2 H), 4.26 (s, 2 H), 4.21 (br. s, 1 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 161.3 (d, J = 251.0 Hz), 145.9, 136.2
(d, J = 3.1 Hz), 129.3 (d, J = 8.0 Hz), 129.1 (2 CH), 126.4 (d, J =
23.9 Hz), 122.5, 115.4 (d, J = 21.0 Hz), 114.0 (2 CH), 97.4 (d, J =
General Procedure for the N-Alkylation of Iodine Compounds: A
mixture of 2-iodo-4-fluorobenzyl bromide[17] (1.00 equiv.,
0.397 mmol, 125 mg), amine (3.00 equiv., 1.19 mmol), and potas-
sium iodide (0.10 equiv., 0.0397 mmol, 6.6 mg) in acetonitrile
(1.00 mL) in a sealed vial was heated in a microwave reactor
(200 W, ramp time 5–10 min, 170 °C, 15 min hold time). After cool-
ing to room temperature, the reaction mixture was diluted with
dichloromethane (10 mL) and washed with an aqueous saturated
sodium hydrogen carbonate solution (10 mL) and brine (10 mL).
8.1 Hz), 52.4 ppm. IR (film on KBr): ν = 3431 (m), 3065 (vw), 3025
˜
(vw), 2852 (vw), 1862 (vw), 1726 (vw), 1596 (s), 1502 (s), 1476 (s),
1434 (w), 1401 (w) cm–1. UV/Vis (CH3CN): λmax (A) = 230 (0.6),
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254 (0.8), 305 (0.1) nm. MS (EI): m/z (%) = 360 (90) [M]+, 234 (d, J = 20.7 Hz), 114.9 (2 CH), 114.2 (2 CH), 97.4 (d, J = 8.3 Hz),
(100) [M – C6H5NCl]+. HRMS (EI): calcd. for C13H10NFClI
360.9531 [M]+; found 360.9528.
55.7, 53.2 ppm. IR (film on KBr): ν = 3416 (vw), 2932 (vw), 2831
˜
(vw), 1592 (w), 1513 (s), 1475 (m), 1408 (vw) cm–1. UV/Vis
(CH3CN): λmax (A) = 231 (1.6), 313 (0.3) nm. MS (EI): m/z (%) =
357 (100) [M]+, 122 (46). HRMS (EI): calcd. for C14H13IFNO
357.0026 [M]+; found 357.0025.
N-(2-Iodo-4-fluorobenzyl)-3,5-bis(trifluoromethyl)aniline (17a): The
crude product was purified by flash chromatography (cyclohexane/
EtOAc = 5:1) and the product obtained as a white solid in 85%
(156 mg, 0.337 mmol) yield. Rf = 0.5 (Cy-Hex/EtOAc = 5:1), m.p.
55–57 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.62 (dd, J = 7.9,
General Procedure for the N-Alkylation of Bromine Compounds: A
mixture of 2-bromo-4-fluorobenzyl bromide (1.00 equiv., 0.5 mmol,
2.6 Hz, 1 H), 7.31 (dd, J = 7.9, 5.8 Hz, 1 H), 7.21 (s, 1 H), 7.07 134 mg), amine (3.00 equiv., 1.5 mmol), and potassium iodide
(dt, J = 8.3, 2.6 Hz, 1 H), 6.96 (s, 2 H), 4.56 (t, J = 5.6 Hz, 1 H), (0.10 equiv., 0.05 mmol, 8 mg) in acetonitrile (1.50 mL) in a sealed
4.37 (d, J = 5.6 Hz, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = vial was heated in a microwave reactor (200 W, ramp time 5–
161.6 (d, J = 252.0 Hz), 148.0, 135.3 (d, J = 3.4 Hz), 132.6 (q, J = 10 min, 170 °C, 15 min hold time). After cooling to room tempera-
32.8 Hz, 2 Cquart.), 123.4 (d, J = 8.3 Hz), 127.5, 126.8 (d, J = ture the reaction mixture was diluted with dichloromethane
24.0 Hz), 124.8, 122.1, 119.4, 115.6 (d, J = 20.8 Hz), 112.1 (d, J = (10 mL) and washed with an aqueous saturated sodium hydrogen
3.3 Hz), 110.9 (sept., J = 3.8 Hz), 97.8 (d, J = 8.1 Hz), 51.9 ppm. carbonate solution (10 mL) and brine (10 mL). Then the solution
IR (ATR): ν = 3451 (vw), 1619 (w), 1583 (w), 1517 (w), 1473 (w),
was dried (MgSO4) and the solvent evaporated. The crude product
was purified by flash chromatography.
˜
1443 (vw), 1424 (w) cm–1. UV/Vis (CH3CN): λmax (A) = 229 (1.1),
259 (1.6), 318 (0.3) nm. MS (EI): m/z (%) = 463 (79) [M]+, 234
(100) [M – C8H4NF6]+. HRMS (EI): calcd. for C15H9NIF7
462.9668 [M]+; found 462.9669.
N-(2-Bromo-4-fluorobenzyl)aniline (13b): The crude product was
purified by flash chromatography (cyclohexane/EtOAc = 5:1) and
the product obtained as
a colorless oil in 92% (129 mg,
N-(2-Iodo-4-fluorobenzyl)biphenyl-2-amine (18a): The crude prod-
uct was purified by flash chromatography (cyclohexane/EtOAc =
5:1) and the product obtained as a white solid in 91% (146 mg,
0.460 mmol) yield. Rf = 0.48 (Cy-Hex/EtOAc = 5:1). 1H NMR
(CDCl3, 400 MHz): δ = 7.39 (dd, J = 6.1, 8.6 Hz, 1 H), 7.34 (dd,
J = 8.1, 2.6 Hz, 1 H), 7.22–7.16 (m, 2 H), 6.99 (dt, J = 8.3, 2.6 Hz,
1 H), 6.75 (tt, J = 7.3, 1.0 Hz, 1 H), 6.62–6.59 (m, 2 H), 4.38 (s, 2
0.362 mmol) yield. Rf = 0.28 (Cy-Hex/EtOAc = 5:1), m.p. 98–
1
99 °C. H NMR (CDCl3, 300 MHz): δ = 7.67 (dd, J = 7.9, 1.3 Hz, H), 4.19 (br. s, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.5
1 H), 7.61–7.52 (m, 4 H), 7.50–7.42 (m, 1 H), 7.39 (dd, J = 7.8, (d, J = 249.6 Hz), 147.5, 134.0 (d, J = 3.3 Hz), 130.0 (d, J =
6.5 Hz, 1 H), 7.32–7.23 (m, 2 H), 7.14–7.09 (m, 1 H), 6.91 (t, J =
7.3 Hz, 1 H), 6.60 (d, J = 8.1 Hz, 1 H), 4.63 (br. s, 1 H), 4.35 (s, 2
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.1 (d, J = 250.5 Hz),
144.1, 139.2, 136.6 (d, J = 2.7 Hz), 130.2, 129.4 (2 CH), 129.1,
128.9 (2 CH), 128.7, 127.8, 127.3, 126.2 (d, J = 23.8 Hz), 117.6,
115.2 (d, J = 20.7 Hz), 110.7, 97.1 (d, J = 8.1 Hz), 52.5 ppm. IR
8.5 Hz), 129.9, 122.9 (d, J = 9.6 Hz), 120.0 (d, J = 24.7 Hz), 117.9,
114.6 (d, J = 20.7 Hz), 112.9, 47.8 ppm. IR (film on KBr): ν = 3419
˜
(m), 3053 (w), 3022 (w), 2921 (w), 1603 (s), 1507 (s), 1482 (s) cm–1.
UV/Vis (CH3CN): λmax (A) = 245 (0.7), 274 (0.2), 292 (0.1) nm.
MS (EI): m/z (%) = 279/281 (86/84) [M]+, 187/189 (100/94) [M –
C6H5N]+. HRMS (EI): calcd. for C13H11NFBr 279.0059 [M]+;
(ATR): ν = 3412 (w), 3053 (vw), 2877 (vw), 1890 (vw), 1591 (w), found 279.0056.
˜
1578 (m), 1507 (m), 1488 (w), 1473 (m), 1438 (w), 1425 (w) cm–1.
UV/Vis (CH3CN): λmax (A) = 227 (1.4), 310 (0.2) nm. MS (EI): m/z
(%) = 403 (100) [M]+, 180 (47), 168 (37). HRMS (EI): calcd. for
C19H15IFN 403.0233 [M]+; found 403.0234.
Methyl 2-(2-Bromo-4-fluorobenzylamino)benzoic Acid (14b): The
crude product was purified by flash chromatography (cyclohexane/
EtOAc = 5:1) and the product obtained as a yellow solid in 85%
(144 mg, 0.425 mmol) yield. Rf = 0.49 (Cy-Hex/EtOAc = 5:1), m.p.
103–105 °C. 1H NMR (CDCl3, 400 MHz): δ = 8.25 (br. s, 1 H),
7.94 (dt, J = 8.0, 1.6 Hz, 1 H), 7.35–7.27 (m, 3 H), 6.96 (dt, J =
8.3, 2.6 Hz, 1 H), 6.65–6.61 (m, 1 H), 6.50 (d, J = 8.5 Hz, 1 H),
4.47 (d, J = 5.5 Hz, 2 H), 3.89 (s, 3 H) ppm. 13C NMR (CDCl3,
N-(2-Iodo-4-fluorobenzyl)-4-nitroaniline (19a): The crude product
was purified by flash chromatography (cyclohexane/EtOAc = 5:1)
and the product obtained as a yellow solid in 72% (107 mg,
0.288 mmol) yield. Rf = 0.29 (Cy-Hex/EtOAc = 5:1), m.p. 159–
161 °C. 1H NMR (CDCl3, 400 MHz): δ = 8.11–8.06 (m, 2 H), 7.62 100 MHz): δ = 169.1, 161.5 (d, J = 249.6 Hz), 150.5, 134.7, 133.5
(dd, J = 7.8, 2.5 Hz, 1 H), 7.28–7.24 (m, 1 H), 7.05 (dt, J = 8.2,
(d, J = 3.5 Hz), 131.7, 129.4 (d, J = 8.3 Hz), 122.8 (d, J = 9.6 Hz),
2.5 Hz, 1 H), 6.57–6.52 (m, 2 H), 4.94 (br. s, 1 H), 4.40 (d, J = 120.0 (d, J = 24.6 Hz), 115.4, 114.6 (d, J = 20.8 Hz), 111.6, 110.5,
5.8 Hz, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.5 (d, J
= 252.3 Hz), 152.5, 138.7, 135.0 (d, J = 3.4 Hz), 129.3 (d, J =
8.1 Hz), 126.8 (d, J = 23.7 Hz), 126.4 (2 CH), 115.6 (d, J =
21.1 Hz), 111.5 (2 CH), 97.6 (d, J = 8.3 Hz), 51.7 ppm. IR (ATR):
51.6, 46.5 ppm. IR (ATR): ν = 3361 (vw), 2958 (vw), 1682 (w),
˜
1581 (w), 1517 (w), 1478 (w), 1462 (w) cm–1. UV/Vis (CH3CN):
λmax (A) = 220 (1.8), 255 (0.5), 346 (0.3) nm. MS (EI): m/z (%) =
337/339 (100/97) [M]+, 304/306 (47/51), 276/278 (16/17), 187/189
ν = 3334 (w), 1593 (m), 1579 (m), 1531 (w), 1494 (w), 1472 (49/46). HRMS (EI): calcd. for C15H13BrFNO2 337.0114 [M]+;
˜
(m) cm–1. UV/Vis (CH3CN): λmax (A) = 228 (0.6), 227 (0.1), 374 found 337.0115.
(0.6) nm. MS (EI): m/z (%) = 371 (92) [M]+, 234 (100) [M –
3-(2-Bromo-4-fluorobenzylamino)phenol (15b): The crude product
C6H5N2O2]+. HRMS (EI): calcd. for C13H10IFN2O2 371.9771
was purified by flash chromatography (cyclohexane/EtOAc = 2:1)
[M]+; found 371.9770.
and the product obtained as a white solid in 74% (110 mg,
N-(2-Iodo-4-fluorobenzyl)-4-methoxyaniline (20): The crude product
was purified by flash chromatography (cyclohexane/EtOAc = 5:1)
and the product obtained as a yellow oil in 85% (120 mg, 0.336)
yield. Rf = 0.37 (Cy-Hex/EtOAc = 5:1). 1H NMR (CDCl3,
0.370 mmol) yield. Rf = 0.40 (Cy-Hex/EtOAc = 2:1), m.p. 89–
91 °C. H NMR (CDCl3, 400 MHz): δ = 7.35–7.30 (m, 2 H), 7.01
1
(d, J = 8.0 Hz, 1 H), 6.95 (dt, J = 8.3, 2.6 Hz, 1 H), 6.25–6.18 (m,
2 H), 6.09–6.06 (m, 1 H), 4.30 (s, 2 H) ppm. 13C NMR (CDCl3,
400 MHz): δ = 7.59 (dd, J = 8.0, 2.6 Hz, 1 H), 7.35 (dd, J = 8.6, 100 MHz): δ = 161.5 (d, J = 249.6 Hz), 156.5, 149.0, 133.7 (d, J =
6.0 Hz, 1 H), 7.03 (dt, J = 8.3, 2.6 Hz, 1 H), 6.81–6.78 (m, 2 H),
6.58–6.54 (m, 2 H), 4.24 (s, 2 H), 3.75 (s, 3 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 161.2 (d, J = 250.4 Hz), 152.4, 141.5, 137.0
(d, J = 3.3 Hz), 129.4 (d, J = 8.0 Hz), 126.2 (d, J = 23.9 Hz), 115.3
3.3 Hz), 130.3, 130.0 (d, J = 8.3 Hz), 122.9 (d, J = 9.6 Hz), 120.2
(d, J = 24.4 Hz), 114.5 (d, J = 20.8 Hz), 106.1, 105.1, 100.0,
47.7 ppm. IR (ATR): ν = 3414 (m), 3312 (w), 1623 (m), 1585 (m),
˜
1514 (m), 1495 (m), 1479 (m) cm–1. UV/Vis (CH3CN): λmax (A) =
6
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O30218
/KAP1
Date: 08-05-13 18:18:24
Pages: 11
Photochemical Synthesis of Phenanthridines
246 (0.5), 275 (0.1), 292 (0.1) nm. MS (EI): m/z (%) = 295/297 (83/
[M]+, 187/189 (100/95) [M – C6H5N2O2]+. HRMS (EI): calcd. for
83) [M]+, 214/216 (69/91), 187/189 (100/94) [M – C6H6NO]+, 108 C13H10BrFN2O2 323.9910 [M]+; found 323.9908.
(68). HRMS (EI): calcd. for C13H11BrFNO 295.0008 [M]+; found
295.0011.
N-(2-Bromo-4-fluorobenzyl)-2-methoxy-4-nitroaniline (30): The
crude product was purified by flash chromatography (cyclohexane/
EtOAc = 5:1) and the product obtained as a yellow solid in 82%
(146 mg, 0.410 mmol) yield. Rf = 0.21 (Cy-Hex/EtOAc = 5:1), m.p.
114–116 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.82 (dd, J = 8.8,
2.2 Hz, 1 H), 7.64 (d, J = 2.2 Hz, 1 H), 7.34 (dd, J = 8.0, 2.4 Hz,
1 H), 7.29–7.24 (m, 1 H), 6.99 (dt, J = 8.2, 2.5 Hz, 1 H), 6.39 (d,
J = 8.8 Hz, 1 H), 5.50 (br. s, 1 H), 4.49 (d, J = 5.9 Hz, 2 H), 3.95
(s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.8 (d, J =
250.9 Hz), 145.3, 143.3, 137.8, 132.3 (d, J = 3.4 Hz), 129.7 (d, J =
8.3 Hz), 123.2 (d, J = 9.6 Hz), 120.4 (d, J = 24.6 Hz), 119.5, 114.8
N-(2-Bromo-4-fluorobenzyl)-4-chloroaniline (16b): The crude prod-
uct was purified by flash chromatography (cyclohexane/EtOAc =
5:1) and the product obtained as a yellow oil in 94% (148 mg,
1
0.470) yield. Rf = 0.53 (Cy-Hex/EtOAc = 5:1). H NMR (CDCl3,
400 MHz): δ = 7.36–7.31 (m, 2 H), 7.13–7.10 (m, 2 H), 6.99 (dt, J
= 8.3, 2.6 Hz, 1 H), 6.53–6.49 (m, 2 H), 4.34 (s, 2 H), 4.20 (br. s, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.6 (d, J = 250.0 Hz),
146.0, 133.5 (d, J = 3.4 Hz), 129.9 (d, J = 8.5 Hz), 129.1 (2 CH),
123.0 (d, J = 9.6 Hz), 122.5, 120.1 (d, J = 24.4 Hz), 114.6 (d, J =
(d, J = 20.8 Hz), 107.1, 104.8, 55.9, 46.7 ppm. IR (KBr): ν = 3339
˜
20.8 Hz), 114.0 (2 CH), 47.8 ppm. IR (film on KBr): ν = 3433 (w),
˜
(w), 2928 (vw), 1594 (w), 1541 (w), 1484 (w) cm–1. UV/Vis
3070 (vw), 2923 (vw), 1599 (m), 1502 (m), 1482 (m) cm–1. UV/Vis
(CH3CN): λmax (A) = 254 (0.9), 306 (0.1) nm. MS (EI): m/z (%) =
313/315 (98/83) [M]+, 187/189 (100/96) [M – C6H5NCl]+. HRMS
(EI): calcd. for C13H10NFClBr 312.9669 [M]+; found 312.9670.
(CH3CN): λmax (A) = 262 (0.2), 382 (0.6), 393 (0.6) nm. MS (EI):
m/z (%)
= –
354/356 (72/73) [M]+, 187/189 (100/97) [M
C7H7N2O3]+. HRMS (EI): calcd. for C14H12FBrN2O3 354.0015
[M]+; found 354.0017.
N-(2-Bromo-4-fluorobenzyl)-3,5-bis(trifluoromethyl)aniline
(17b):
Synthesis of the N-Alkylated Bromo Derivatives 35 and 36: Com-
pounds 35 and 36 were synthesized by following the above general
procedure but by starting from 2-bromo-5-fluorobenzyl bromide
(1.00 equiv., 0.5 mmol, 134 mg), amine (3.00 equiv., 1.5 mmol), and
potassium iodide (0.10 equiv., 0.05 mmol, 8 mg) in acetonitrile
(1.50 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 5:1) and the product obtained as a white solid in
74% (154 mg, 0.370 mmol) yield. Rf = 0.42 (Cy-Hex/EtOAc = 5:1),
1
m.p. 71–73 °C. H NMR (CDCl3, 400 MHz): δ = 7.28–7.32 (m, 2
H), 7.19 (s, 1 H), 7.03 (dt, J = 8.2, 2.6 Hz, 1 H), 6.96 (s, 2 H), 4.56
(br. s, 1 H), 4.43 (s, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ =
161.8 (d, J = 251.3 Hz), 148.1, 132.6 (q, J = 32.8 Hz, 2 Cquart.),
132.4, 130.2 (d, J = 8.6 Hz), 123.4 (q, J = 272.7 Hz, 2 CF3), 123.4
(d, J = 9.6 Hz), 120.6 (d, J = 24.4 Hz), 114.9 (d, J = 21.0 Hz), 112.1
(d, J = 3.3 Hz, 2 CH), 110.9 (sept., J = 3.8 Hz), 47.5 ppm. IR
N-(2-Bromo-5-fluorobenzyl)aniline (35): The crude product was
purified by flash chromatography (cyclohexane/EtOAc = 5:1) and
the product obtained as
a colorless oil in 90% (198 mg,
0.450 mmol) yield. Rf = 0.65 (Cy-Hex/EtOAc = 5:1). 1H NMR
(CDCl3, 400 MHz): δ = 7.53 (dd, J = 5.2, 8.7 Hz, 1 H), 7.23–7.17
(m, 3 H), 6.87 (dt, J = 8.2, 3.1 Hz, 1 H), 6.77 (t, J = 7.3 Hz, 1 H),
6.62–6.58 (m, 2 H), 4.39 (t, J = 4.2 Hz, 2 H), 4.24 (br. s, 1 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 162.4 (d, J = 247.1 Hz), 147.3,
140.8 (d, J = 6.8 Hz), 133.9 (d, J = 7.9 Hz), 129.3 (2 CH), 118.0,
116.7 (d, J = 3.0 Hz), 116.0 (d, J = 23.8 Hz), 115.6 (d, J = 22.8 Hz),
(ATR): ν = 3454 (vw), 1620 (w), 1596 (w), 1518 (w), 1478 (w) cm–1.
˜
UV/Vis (CH3CN): λmax (A) = 258 (2.2), 318 (0.3) nm. MS (EI): m/z
(%) = 415/417 (19/20) [M]+, 187/189 (100/95). HRMS (EI): calcd.
for C15H9NBrF7 414.9807 [M]+; found 414.9810.
N-(2-Bromo-4-fluorobenzyl)biphenyl-2-amine (18b): The crude
product was purified by flash chromatography (cyclohexane/EtOAc
= 5:1) and the product obtained as a white solid in 97% (172 mg,
0.485 mmol) yield. Rf = 0.37 (Cy-Hex/EtOAc = 5:1), m.p. 118–
120 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.47–7.41 (m, 4 H), 7.35–
7.25 (m, 3 H), 7.17–7.09 (m, 2 H), 6.92 (dt, J = 8.3, 2.6 Hz, 1 H),
6.77 (dt, J = 7.4, 1.0 Hz, 1 H), 6.49 (d, J = 8.1 Hz, 1 H), 4.47 (br.
s, 1 H), 4.28 (s, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.4
(d, J = 249.6 Hz), 144.2, 139.2, 133.9 (d, J = 3.4 Hz), 130.2, 129.6
(d, J = 8.2 Hz), 129.3 (2 CH), 128.9 (2 CH), 128.7, 127.8, 127.3,
122.7 (d, J = 9.5 Hz), 119.9 (d, J = 24.6 Hz), 117.5, 114.5 (d, J =
112.9 (2 CH), 48.3 ppm. IR (film on KBr): ν = 3420 (w), 3052 (vw),
˜
2921 (vw), 1603 (m), 1580 (w), 1506 (m), 1463 (w) cm–1. UV/Vis
(CH3CN): λmax (A) = 245 (1.0), 276 (0.2), 293 (0.2) nm. MS (EI):
m/z (%) = 279/281 (68/68) [M]+, 198/200 (72/100) [M – C6H6]+,
187/189 (57/27). HRMS (EI): calcd. for C13H11NFBr 279.0059
[M]+; found 279.0060.
Methyl 2-(2-Bromo-5-fluorobenzylamino)benzoic Acid (36): The
crude product was purified by flash chromatography (cyclohexane/
EtOAc = 5:1) and the product obtained as a yellow solid in 72%
(121 mg, 0.358 mmol) yield. Rf = 0.65 (Cy-Hex/EtOAc = 5:1) M.p.
20.8 Hz), 110.7, 47.7 ppm. IR (ATR): ν = 3441 (vw), 3074 (vw),
˜
2923 (vw), 1885 (vw), 1593 (w), 1580 (w), 1509 (w), 1488 (w) cm–1.
UV/Vis (CH3CN): λmax (A) = 222 (1.0), 309 (0.2) nm. MS (EI): m/z
(%) = 355/357 (100/96) [M]+, 168 (71), 108 (52). HRMS (EI): calcd.
for C19H15BrFN 355.0372 [M]+; found 355.0374.
1
106–108 °C. H NMR (CDCl3, 400 MHz): δ = 8.32 (t, J = 5.7 Hz,
1 H), 7.96 (dd, J = 8.0, 1.6 Hz, 1 H), 7.52 (dd, J = 8.7, 5.2 Hz, 1
H), 7.33–7.27 (m, 1 H), 7.08 (dd, J = 9.5, 3.0 Hz, 1 H), 6.86 (dt, J
= 8.2, 3.1 Hz, 1 H), 6.67–6.62 (m, 1 H), 6.46 (d, J = 8.4 Hz, 1 H),
4.48 (d, J = 6.2 Hz, 2 H), 3.90 (s, 3 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 169.1, 162.4 (d, J = 249.6 Hz), 150.4, 140.2 (d, J =
6.7 Hz), 134.7, 133.9 (d, J = 7.8 Hz), 131.7, 116.6 (d, J = 3.1 Hz),
115.6 (d, J = 22.5 Hz), 115.5 (d, J = 24.1 Hz), 115.5, 111.5, 110.6,
N-(2-Bromo-4-fluorobenzyl)-4-nitroaniline (19b): The crude product
was purified by flash chromatography (cyclohexane/EtOAc = 5:1)
and the product obtained as a yellow solid in 63% (102 mg,
0.315 mmol) yield. Rf = 0.38 (Cy-Hex/EtOAc = 2:1), m.p. 165–
168 °C. 1H NMR (CDCl3, 400 MHz): δ = 8.10–8.06 (m, 2 H), 7.37
(dd, J = 8.0, 2.6 Hz, 1 H), 7.30 (dd, J = 8.6, 5.9 Hz, 1 H), 7.01 (dt,
J = 8.6, 2.6 Hz, 1 H), 6.58–6.54 (m, 2 H), 4.98 (br. s, 1 H), 4.47 (d,
J = 5.9 Hz, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.9 (d,
J = 251.4 Hz), 152.6, 138.7, 132.2 (d, J = 3.5 Hz), 129.9 (d, J =
8.3 Hz), 126.4 (2 CH), 123.2 (d, J = 9.6 Hz), 120.5 (d, J = 24.5 Hz),
51.6 (OCH ), 47.0 ppm. IR (ATR): ν = 3356 (w), 2953 (vw), 1679
˜
3
(m), 1603 (w), 1579 (m), 1517 (w), 1456 (w) cm–1. UV/Vis
(CH3CN): λmax (A) = 220 (1.4), 254 (0.5), 346 (0.3) nm. MS (EI):
m/z (%) = 337/339 (88/91) [M]+, 304/306 (49/49), 226 (100), 198
(92). HRMS (EI): calcd. for C15H13BrFNO2 337.0114 [M]+; found
337.0113.
114.9 (d, J = 21.1 Hz), 111.5 (2 CH), 47.2 ppm. IR (ATR): ν =
N-[(6-Iodobenzo[d][1,3]dioxol-5-yl)methyl]aniline (41a): A mixture
˜
3332 (w), 1597 (m), 1538 (w), 1473 (m) cm–1. UV/Vis (CH3CN): of 5-(bromomethyl)-6-iodobenzo[d][1,3]dioxole[18] (1.00 equiv.,
λmax (A) = 373 (0.5) nm. MS (EI): m/z (%) = 324/326 (16/15)
0.324 mmol, 110 mg), aniline (3.00 equiv., 0.971 mmol), and potas-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O30218
/KAP1
Date: 08-05-13 18:18:24
Pages: 11
A. M. Linsenmeier, C. M. Williams, S. Bräse
FULL PAPER
sium iodide (0.10 equiv., 0.0324 mmol, 5.38 mg) in acetonitrile
(1.00 mL) in a sealed vial was heated in a microwave reactor
(200 W, ramp time 5–10 min, 170 °C, 15 min hold time). After cool-
ing to room temperature the reaction mixture was diluted with
dichloromethane (10 mL) and washed with an aqueous saturated
sodium hydrogen carbonate solution (10 mL) and brine (10 mL).
Then the solution was dried (MgSO4) and the solvent evaporated.
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 5:1) and the product obtained as a white solid in
77% (88.0 mg, 0.249 mmol) yield. Rf = 0.42 (Cy-Hex/EtOAc = 5:1),
m.p. 85–87 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.27 (s, 1 H),
7.21–7.17 (m, 2 H), 6.94 (s, 1 H), 6.76–6.72 (m, 1 H), 6.60–6.58 (m,
2 H), 5.95 (s, 2 H), 4.24 (s, 2 H), 4.16 (br. s, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 148.6, 147.6, 147.5, 134.5, 129.3 (2 CH),
118.6, 117.8, 112.9 (2 CH), 109.0, 101.6, 85.8, 53.1 ppm. IR (ATR):
(s, 2 H), 4.27 (s, 2 H), 4.18 (br. s, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 147.6 (2 Cquart.), 146.1, 131.0, 129.1 (2 CH), 122.4,
114.0 (2 CH), 113.3, 112.9, 109.0, 101.7, 48.3 ppm. IR (ATR): ν =
˜
3435 (w), 2903 (w), 1852 (vw), 1596 (w), 1496 (m), 1476 (m) cm–1.
UV/Vis (CH3CN): λmax (A) = 254 (1.5), 295 (0.5) nm. MS (EI): m/z
(%) = 339/341 (33/41) [M]+, 213/215 (100/100) [M – C6H4NCl]+.
HRMS (EI): calcd. for C14H11NClBrO2 338.9662 [M]+; found
338.9660.
N-[(6-Bromobenzo[d][1,3]dioxol-5-yl)methyl]-2-fluoroaniline
(44):
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 5:1) and the product obtained as a white solid in
82% (133 mg, 0.0410 mmol) yield. Rf = 0.47 (Cy-Hex/EtOAc =
1
5:1), m.p. 103–105 °C. H NMR (CDCl3, 400 MHz): δ = 7.04 (s, 1
H), 7.02–6.95 (m, 2 H), 6.91 (s, 1 H), 6.68–6.58 (m, 2 H), 5.95 (s,
2 H), 4.46 (br. s, 1 H), 4.35 (d, J = 5.9 Hz, 2 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 151.5 (d, J = 238.5 Hz), 147.6, 147.5, 136.0
(d, J = 11.3 Hz), 131.0, 124.6 (d, J = 3.4 Hz), 117.1 (d, J =
10.9 Hz), 114.4 (d, J = 24.6 Hz), 113.2, 112.8, 112.4 (d, J = 3.4 Hz),
ν = 3423 (w), 3018 (vw), 2897 (vw), 1598 (m), 1512 (w), 1499 (w),
˜
1469 (m), 1438 (w), 1405 (w) cm–1. UV/Vis (CH3CN): λmax (A) =
245 (1.3), 294 (0.4) nm. MS (EI): m/z (%) = 352 (28) [M]+, 260 (49),
135 (34), 43 (100). HRMS (EI): calcd. for C14H12INO2 352.9913
[M]+; found 352.9916.
108.8, 101.7, 47.8 ppm. IR (ATR): ν = 3420 (w), 2914 (vw), 1621
˜
(m), 1516 (m), 1502 (m), 1476 (m) cm–1. UV/Vis (CH3CN): λmax
(A) = 201 (2.2), 242 (0.7), 288 (0.3) nm. MS (EI): m/z (%) = 323/
Synthesis of the N-Alkylated Bromo Derivatives 41a and 42–45:
Compounds 41a and 42–45 were synthesized by following the
above general procedure but by starting from 5-bromo-6-
325 (53/56) [M]+, 244/246 (13/18), 215/213 (100/95) [M
–
C6H4NF]+. HRMS (EI): calcd. for C14H11BrFNO2 322.9957 [M]+;
found 322.9957.
(bromomethyl)benzo[d][1,3]dioxole
(1.00 equiv.,
0.5 mmol,
147 mg), amine (3.00 equiv., 1.5 mmol), and potassium iodide
(0.10 equiv., 0.05 mmol, 8 mg) in acetonitrile (1.50 mL).
N-[(6-Bromobenzo[d][1,3]dioxol-5-yl)methyl]biphenyl-2-amine (45):
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 5:1) and the product obtained as a white solid in
41% (78.7 mg, 0.206 mmol) yield. Rf = 0.47 (Cy-Hex/EtOAc =
10:1), m.p. 133–136 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.51–
7.45 (m, 4 H), 7.41–7.34 (m, 1 H), 7.23–7.18 (m, 1 H), 7.13 (dd, J
= 7.4, 1.4 Hz, 1 H), 7.02 (s, 1 H), 6.88 (s, 1 H), 6.83–6.78 (m, 1 H),
6.59–6.56 (m, 1 H), 5.94 (s, 2 H), 4.50 (br. s, 1 H), 4.28 (s, 2 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 147.5, 147.3, 144.3, 139.3, 131.5,
130.2, 129.4 (2 CH), 128.9 (2 CH), 128.7, 127.8, 127.3, 117.4, 113.1,
N-[(6-Bromobenzo[d][1,3]dioxol-5-yl)methyl]aniline (41b): The crude
product was purified by flash chromatography (cyclohexane/EtOAc
= 5:1) and the product obtained as a yellow solid in 75% (115 mg,
0.375 mmol) yield. Rf = 0.29 (Cy-Hex/EtOAc = 10:1), m.p. 94–
1
96 °C. H NMR (CDCl3, 400 MHz): δ = 7.24–7.20 (m, 2 H), 7.06
(s, 1 H), 6.95 (s, 1 H), 6.78 (t, J = 7.3 Hz, 1 H), 6.64 (d, J = 7.8 Hz,
2 H), 5.95 (s, 2 H), 4.32 (s, 2 H), 4.21 (br. s, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 147.5 (2 Cquart.), 147.3, 131.4, 129.2 (2 CH),
117.7, 113.2, 112.9 (2 CH), 112.7, 109.0, 101.6, 48.2 ppm. IR
112.8, 110.8, 108.8, 101.6, 48.3 ppm. IR (ATR): ν = 3439 (w), 2897
˜
˜
(vw), 1593 (w), 1579 (w), 1503 (m), 1473 cm–1. UV/Vis (CH3CN):
λmax (A) = 296 (0.09) nm. MS (EI): m/z (%) = 381/383 (97/100)
[M]+, 302/300 (23/42). 213/215 (57/58) [M – C12H10N]+. HRMS
(EI): calcd. for C20H16NBrO2 381.0364 [M]+; found 381.0366.
(ATR): ν = 3423 (w), 3022 (vw), 2870 (vw), 1599 (m), 1465
(m) cm–1. UV/Vis (CH3CN): λmax (A) = 203 (2.2), 246 (0.7), 294
(0.3) nm. MS (EI): m/z (%) = 307/305 (53/56) [M]+, 226/224 (13/
18), 215/213 (100/95) [M – C6H5N]+. HRMS (EI): calcd. for
C14H12BrNO2 305.0051 [M]+; found 305.0054.
General Procedure for the Cyclization Reaction: The N-alkylated
material was dissolved in anhydrous acetonitrile in a quartz flask.
The mixture was irradiated (irradiation conditions: Rayonet photo-
chemical reactor using lamps of λ = 254 nm) under argon for 2 h.
The solvent was evaporated and the crude product purified by flash
chromatography. Most compounds were isolated as white or yellow
solids that turned brown after a short time on exposure to the
atmosphere.
Methyl-2-[(6-Bromobenzo[d][1,3]dioxol-5-yl)methylamino]benzoic
Acid (42): The crude product was purified by flash chromatography
(cyclohexane/EtOAc = 5:1) and the product obtained as a white
solid in 64% (94.0 mg, 0.259 mmol) yield. Rf = 0.34 (Cy-Hex/
1
EtOAc = 10:1), m.p. 147–149 °C. H NMR (CDCl3, 400 MHz): δ
= 8.21 (br. s, 1 H), 7.93 (dd, J = 7.9, 1.6 Hz, 1 H), 7.32–7.28 (m, 1
H), 7.03 (s, 1 H), 6.84 (s, 1 H), 6.64–6.60 (m, 1 H), 6.52 (d, J =
8.5 Hz, 1 H), 5.93 (s, 2 H), 4.40 (d, J = 6.0 Hz, 2 H), 4.28 (s, 3
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 169.1, 150.6, 147.7,
147.4, 134.6, 131.6, 131.0, 115.2, 113.1, 112.8, 111.6, 110.4, 108.5,
9-Fluorophenanthridine (21): Amine 13a (30.0 mg, 0.0920 mmol,
1.00 equiv.) was dissolved in dry acetonitrile (30 mL). The crude
product was purified by flash chromatography (cyclohexane/EtOAc
= 1:1) and the product obtained as a yellow solid in 76% (13.7 mg,
0.0695 mmol) yield.
101.6, 51.5, 47.0 ppm. IR (ATR): ν = 3368 (w), 2910 (w), 1678 (m),
˜
1602 (w), 1577 (m), 1515 (m), 1498 (m), 1471 (m) cm–1. UV/Vis
(CH3CN): λmax (A) = 219 (2.5), 254 (1.0), 294 (0.3), 349 (0.5) nm.
MS (EI): m/z (%) = 363/365 (62/65) [M]+, 213/215 (100/99) [M –
C8H7NO2]+. HRMS (EI): calcd. for C16H14NBrO4 363.0106 [M]+;
found 363.0105.
Amine 13b (40.0 mg, 0.1430 mmol, 1.00 equiv.) was dissolved in
dry acetonitrile (40 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow solid in 27% (7.50 mg, 0.0381 mmol) yield.
N-[(6-Bromobenzo[d][1,3]dioxol-5-yl)methyl]-4-chloroaniline
(43):
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 5:1) and the product obtained as a yellow solid
in 67% (114 mg, 0.336 mmol) yield. Rf = 0.30 (Cy-Hex/EtOAc =
10:1) M.p. 109–111 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.13–
7.09 (m, 2 H), 7.02 (s, 1 H), 6.86 (s, 1 H), 6.53–6.49 (m, 2 H), 5.95
Rf = 0.26 (Cy-Hex/EtOAc = 1:1), m.p. 90–94 °C 1H NMR (CDCl3,
400 MHz): δ = 9.26 (s, 1 H), 8.47 (d, J = 8.1 Hz, 1 H), 8.23–8.19
(m, 2 H), 8.07 (dd, J = 8.7, 5.7 Hz, 1 H), 7.81–7.77 (m, 1 H), 7.72–
7.68 (m, 1 H), 8.07 (dt, J = 8.5, 2.4 Hz, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 164.2 (d, J = 251.9 Hz), 152.6, 144.5, 134.8
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O30218
/KAP1
Date: 08-05-13 18:18:24
Pages: 11
Photochemical Synthesis of Phenanthridines
(d, J = 9.6 Hz), 131.4 (d, J = 9.9 Hz), 130.2, 129.4, 127.2, 123.6 (d, nitrile (30 mL). The crude product was purified by flash
J = 4.3 Hz), 123.4 (d, J = 1.2 Hz), 122.4, 116.8 (d, J = 24.2 Hz), chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
107.2 (d, J = 22.6 Hz) ppm. IR (ATR): ν = 3058 (w), 2922 (w),
tained as a yellow solid in 95% (20.5 mg, 0.0615 mmol) yield.
˜
1684 (vw), 1622 (m), 1589 (m), 1524 (w), 1494 (m), 1459 (m) cm–1.
MS (EI): m/z (%) = 197 (100) [M]+, 169 (17), 98 (9). HRMS (EI):
calcd. for C13H8NF 197.0641 [M]+; found 197.0639.
Amine 17b (40.0 mg, 0.0960 mmol, 1.00 equiv.) was dissolved in
dry acetonitrile (40 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow solid in 17% (5.50 mg, 0.0170 mmol) yield.
Rf = 0.20 (Cy-Hex/EtOAc = 5:1), m.p. 76–81 °C. 1H NMR (CDCl3,
400 MHz): δ = 9.36 (s, 1 H), 8.69 (s, 1 H), 8.58 (dd, J = 12.3,
2.0 Hz, 1 H), 8.33 (s, 1 H), 8.18 (dd, J = 8.7, 6.1 Hz, 1 H), 7.67–
7.62 (m, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 164.0 (d, J
= 252.6 Hz), 155.1, 146.1, 132.9 (d, J = 3.6 Hz), 131.8 (d, J =
9.8 Hz), 129.9 (q, J = 34.2 Hz), 127.1 (q, J = 31.8 Hz), 125.1 (d, J
= 1.0 Hz), 124.3 (q, J = 274.0 Hz), 124.3 (d, J = 2.8 Hz), 123.4
(sept., J = 3.8 Hz), 123.2 (q, J = 272.6 Hz), 118.7, (d, J = 24.1 Hz),
Methyl 9-Fluorophenanthridine-4-carboxylate (22): Amine 14a
(30.0 mg, 0.0779 mmol, 1.00 equiv.) was dissolved in dry aceto-
nitrile (30 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow solid in 60% (12.0 mg, 0.0470 mg) yield. Rf =
0.28 (Cy-Hex/EtOAc = 1:1), m.p. 130–131 °C. 1H NMR (CDCl3,
400 MHz): δ = 9.34 (s, 1 H), 8.5 (d, J = 8.2 Hz, 1 H), 8.18 (dd, J
= 10.2, 2.0 Hz, 1 H), 8.08 (dd, J = 8.7, 5.7 Hz, 1 H), 8.00 (dd, J =
7.2, 0.9 Hz, 1 H), 7.70 (t, J = 7.7 Hz, 1 H), 7.47 (dd, J = 8.5,
2.3 Hz, 1 H), 4.08 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ
= 168.7, 164.3 (d, J = 252.9 Hz), 153.5, 141.8, 134.3 (d, J = 9.8 Hz),
132.8, 131.8 (d, J = 9.9 Hz), 129.4, 126.3, 125.2, 123.9 (d, J =
4.4 Hz), 123.2, 117.4 (d, J = 24.2 Hz), 107.3 (d, J = 22.7 Hz),
113.3 (q, J = 9.3 Hz), 113.0 (q, J = 9.3 Hz) ppm. IR (ATR): ν =
˜
2962 (vw), 1674 (m), 1621 (m), 1599 (m), 1530 (m), 1495 (m) cm–1.
MS (EI): m/z (%) = 333 (100) [M]+. HRMS (EI): calcd. for
C15H6NF7 333.0388 [M]+; found 333.0391.
52.7 ppm. IR (ATR): ν = 2946 (vw), 1722 (m), 1624 (w), 1589 (w),
˜
1525 (vw), 1498 (w), 1473 (vw), 1433 (w), 1403 (vw) cm–1. MS (EI):
m/z (%) = 255 (48) [M]+, 197 (100) [M – C2H3O2]+. HRMS (EI):
calcd. for C15H10NO2F 255.0696 [M]+; found 255.0697.
9-Fluoro-4-phenylphenanthridine (26): Amine 18a (30.0 mg,
0.0744 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (30 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 1:1) and the product obtained as a yellow solid
in 95% (19.4 mg, 0.0710 mmol) yield.
9-Fluoro-3-hydroxyphenanthridine (23): Amine 15a (30.0 mg,
0.0875 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (30 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 1:1) and the product obtained as a yellow solid
in 46% (8.50 mg, 0.0399 mmol) yield. Rf = 0.24 (Cy-Hex/EtOAc =
1:1), m.p. 288–292 °C. 1H NMR (CD3OD, 400 MHz): δ = 9.27 (dd,
J = 12.8, 2.5 Hz, 1 H), 9.10 (s, 1 H), 8.14 (dd, J = 8.8, 6.2 Hz, 1
H), 7.55 (s, 1 H), 7.54 (d, J = 2.7 Hz, 1 H), 8.08 (dt, J = 8.4, 2.5 Hz,
1 H), 7.10 (dd, J = 5.9, 3.2 Hz, 1 H) ppm. 13C NMR (CD3OD,
100 MHz): δ = 165.6 (d, J = 248.7 Hz), 158.0, 154.3, 146.9, 136.3
(d, J = 11.6 Hz), 132.8 (d, J = 10.2 Hz), 130.5, 124.9, 120.9, 116.9
(d, J = 24.8 Hz), 114.5 (d, J = 4.0 Hz), 114.2 (d, J = 25.9 Hz),
Amine 18b (40.0 mg, 0.112 mmol, 1.00 equiv.) was dissolved in dry
acetonitrile (40 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow oil in 11% (3.30 mg, 0.0120 mmol) yield.
1
Rf = 0.62 (Cy-Hex/EtOAc = 1:1). H NMR (CDCl3, 400 MHz): δ
= 9.27 (s, 1 H), 8.50 (dd, J = 8.0, 1.6 Hz, 1 H), 8.27 (dd, J = 10.5,
2.3 Hz, 1 H), 8.07 (dd, J = 8.7, 5.7 Hz, 1 H), 7.81–7.73 (m, 2 H),
7.71–7.68 (m, 2 H), 7.54–7.43 (m, 4 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 164.2 (d, J = 251.5 Hz), 152.1, 142.1, 141.9, 139.9,
134.9 (d, J = 9.4 Hz), 131.4 (d, J = 9.7 Hz), 130.7 (2 CH), 128.9,
128.0 (2 CH), 127.3, 126.7, 124.0, 123.1, 121.9, 116.9 (d, J =
114.1 ppm. IR (ATR): ν = 2925 (vw), 2130 (vw), 1952 (vw), 1623
˜
(w), 1602 (w), 1579 (w), 1530 (vw), 1495 (vw), 1456 (w), 1408
(w) cm–1. MS (EI): m/z (%) = 213 (100) [M]+, 185 (20). HRMS
(EI): calcd. for C13H8NOF 213.0590 [M]+; found 213.0592.
24.3 Hz), 107.4 (d, J = 22.6 Hz) ppm. IR (ATR): ν = 3382 (w),
˜
3057 (m), 3026 (m), 2924 (m), 2852 (m), 1941 (vw), 1682 (m), 1625
(m), 1591 (m), 1525 (m), 1503 (m), 1484 (m) cm–1. MS (EI): m/z
(%) = 272 (100) [M]+, 167 (60). HRMS (EI): calcd. for C19H12NF
273.0953 [M]+; found 273.0951.
2-Chloro-9-fluorophenanthridine (24): Amine 16a (30.0 mg,
0.0830 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (30 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 1:1) and the product obtained as a yellow solid
in 79% (15.1 mg, 0.0654 mmol) yield.
9-Fluoro-2-nitrophenanthridine (27): Amine 19a (30.0 mg,
0.0810 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (30 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 1:1) and the product obtained as a yellow solid
in 64% (12.5 mg, 0.0520 mmol) yield. Rf = 0.22 (Cy-Hex/EtOAc =
Amine 16b (40.0 mg, 0.127 mmol, 1.00 equiv.) was dissolved in dry
acetonitrile (40 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow solid in 24% (7.00 mg, 0.0300 mmol) yield.
Rf = 0.19 (Cy-Hex/EtOAc = 1:1), m.p. 150–153 °C. 1H NMR
(CDCl3, 400 MHz): δ = 9.23 (s, 1 H), 8.41 (d, J = 2.3 Hz, 1 H),
8.13 (dd, J = 10.0, 2.3 Hz, 1 H), 8.12 (d, J = 8.8 Hz, 1 H), 8.08
(dd, J = 8.8, 5.7 Hz, 1 H), 7.72 (dd, J = 8.8, 2.3 Hz, 1 H), 7.49 (dt,
J = 8.8, 2.3 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 164.3
(d, J = 253.2 Hz), 152.8, 142.9, 133.8 (d, J = 9.6 Hz), 133.1, 131.7,
131.6 (d, J = 9.8 Hz), 129.9, 124.7 (d, J = 4.3 Hz), 123.5 (d, J =
1.2 Hz), 122.0, 117.6 (d, J = 24.2 Hz), 107.3 (d, J = 22.7 Hz) ppm.
1
1:1), m.p. 256 °C. H NMR (CDCl3, 400 MHz): δ = 9.40 (s, 1 H),
9.37 (d, J = 2.4 Hz, 1 H), 8.56 (dd, J = 9.0, 2.5 Hz, 1 H), 8.34–8.28
(m, 2 H), 8.18 (dd, J = 8.7, 5.5 Hz, 1 H), 7.59 (dt, J = 8.4, 2.4 Hz,
1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 164.8 (d, J =
255.3 Hz), 156.0, 147.5, 145.9, 134.8 (d, J = 9.9 Hz), 132.2 (d, J =
9.8 Hz), 131.8, 123.6, 123.2, 119.1, 118.5 (d, J = 24.1 Hz), 107.8 (d,
J = 23.0 Hz) ppm; 1 quaternary carbon not detected. IR (ATR): ν
˜
= 3065 (vw), 1618 (vw), 1592 (vw), 1540 (vw), 1508 (vw), 1442
(vw) cm–1. MS (EI): m/z (%) = 242 (100) [M]+, 196 (45), 184 (32),
169 (18). HRMS (EI): calcd. for C13H7N2O2F 242.0492 [M]+;
found 242.0491.
IR (ATR): ν = 3055 (w), 1914 (vw), 1684 (vw), 1614 (w), 1588 (w),
˜
1517 (w), 1491 (m) cm–1. MS (EI): m/z (%) = 231 (100) [M]+, 195
(18), 169 (8). HRMS (EI): calcd. for C13H7NFCl 231.0251 [M]+;
found 231.0249.
9-Fluoro-2-methoxyphenanthridine (28): Amine 20 (30.0 mg,
0.0840 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (30 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 1:1) and the product obtained as a yellow solid
in 80% (15.2 mg, 0.0670 mmol) yield. Rf = 0.30 (Cy-Hex/EtOAc =
9-Fluoro-1,3-bis(trifluoromethyl)phenanthridine (25): Amine 17a
(30.0 mg, 0.0648 mmol, 1.00 equiv.) was dissolved in dry aceto-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O30218
/KAP1
Date: 08-05-13 18:18:24
Pages: 11
A. M. Linsenmeier, C. M. Williams, S. Bräse
FULL PAPER
1
1:1), m.p. 129–132 °C. H NMR (CDCl3, 400 MHz): δ = 9.10 (s, 1
H), 8.10 (d, J = 9.0 Hz, 1 H), 8.02 (dd, J = 8.7, 5.7 Hz, 1 H), 7.72
(dd, J = 2.7 Hz, 1 H), 7.44–7.37 (m, 2 H), 4.01 (s, 3 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 163.8 (d, J = 251.5 Hz), 158.5, 150.1,
139.7, 134.1 (d, J = 9.3 Hz), 131.5, 131.4 (d, J = 9.6 Hz), 124.6 (d,
J = 4.0 Hz), 123.4, 119.3, 116.8 (d, J = 24.3 Hz), 107.1 (d, J =
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 2:1) and the product obtained as a yellow solid
in 17% (5.40 mg, 0.0224 mmol) yield. Rf = 0.34 (Cy-Hex/EtOAc =
1
2:1), m.p. 185–189 °C. H NMR (CDCl3, 400 MHz): δ = 9.13 (s, 1
H), 8.15 (d, J = 8.2 Hz, 1 H), 7.88 (s, 1 H), 7.56 (dt, J = 8.1, 5.3 Hz,
1 H), 7.42–7.39 (m, 1 H), 7.37 (s, 1 H), 6.19 (s, 2 H) ppm. 13C
22.4 Hz), 102.9, 55.6 ppm. IR (ATR): ν = 2990 (vw), 1617 (vw), NMR (CDCl3, 100 MHz): δ = 158.9 (d, J = 254.6 Hz), 151.9 (d, J
˜
1524 (vw), 1501 (vw), 1465 (vw), 1430 (vw) cm–1. MS (EI): m/z (%) = 1.1 Hz), 151.8, 148.7, 134.0 (d, J = 11.0 Hz), 129.4 (d, J =
= 227 (100) [M]+, 184 (45), 173 (54), 130 (18). HRMS (EI): calcd.
for C14H10NOF 227.0746 [M]+; found 227.0744.
2.8 Hz), 126.5 (d, J = 8.7 Hz), 126.3, 123.4, 117.6 (d, J = 1.1 Hz),
112.8 (d, J = 19.5 Hz), 105.7, 102.1, 100.3 ppm. IR (ATR): ν =
˜
2913 (vw), 1688 (w), 1619 (w), 1525 (w), 1499 (w), 1468 (m) cm–1.
MS (EI): m/z (%) = 241 (100) [M]+, 136 (99), 111 (32). HRMS (EI):
calcd. for C14H8NFO2 241.0539 [M]+; found 241.0541.
8-Fluorophenanthridine (37): Amine 35 (40.0 mg, 0.143 mmol,
1.00 equiv.) was dissolved in dry acetonitrile (40 mL). The crude
product was purified by flash chromatography (cyclohexane/EtOAc
= 2:1) and the product obtained as a yellow solid in 24% (6.70 mg,
0.0340 mmol) yield. Rf = 0.32 (Cy-Hex/EtOAc = 2:1), m.p. 85–
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of 1, 13a/b–19a/b, 21–28, 30, 35–37,
41a/b, 42–48 and UV spectra of 13a, 14a/b–19a/b, 20, 30, 35, 36,
41a/b, 42, 43, 45.
1
90 °C H NMR (CDCl3, 400 MHz): δ = 9.24 (s, 1 H), 8.62 (dd, J
= 9.0, 5.0 Hz, 1 H), 8.54 (d, J = 8.0 Hz, 1 H), 8.20 (dd, J = 7.9,
1.3 Hz, 1 H), 7.79–7.66 (m, 3 H), 7.62 (dt, J = 8.6, 2.7 Hz, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 161.5 (d, J = 249.2 Hz),
152.3 (d, J = 3.7 Hz), 144.1, 130.3, 129.2 (d, J = 1.5 Hz), 128.6,
127.5, 127.5, 124.6 (d, J = 8.2 Hz), 123.8, 122.0, 120.3 (d, J =
Acknowledgments
23.9 Hz), 112.8 (d, J = 20.6 Hz) ppm. IR (ATR): ν = 3054 (w), The authors thank The University of Queensland and the
˜
1684 (w), 1622 (m), 1597 (m), 1573 (m), 1529 (m), 1480 (m), 1456 Karlsruhe Institute of Technology (KIT) for financial support.
(m) cm–1. MS (EI): m/z (%) = 197 (100) [M]+, 170 (8). HRMS (EI):
calcd. for C13H8NF 197.0641 [M]+; found 197.0640.
[1] a) F. Viladomat, M. Sellés, C. Codina, J. Bastida, Planta Med.
1997, 63, 583; b) A. A. Ali, H. M. El Sayed, O. M. Abdallah,
W. Steglich, Phytochemistry 1986, 25, 2399–2401.
[2] M. E. Budén, V. B. Dorn, M. Gamba, A. B. Pierini, R. A.
Rossi, J. Org. Chem. 2010, 75, 2206–2218.
[1,3]Dioxolo[4,5-j]phenanthridine (Trispheridine, 1): Amine 41a
(30.0 mg, 0.0849 mmol, 1.00 equiv.) was dissolved in dry aceto-
nitrile (30 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow solid in 82% (15.5 mg, 0.0694 mmol) yield.
[3] a) S. N. Sarkar, Nature 1948, 162, 265–266; b) J.-Y. Yao, X.-L.
Li, J.-Y. Shen, X.-Y. Pan, G.-J. Hao, Y. Xu, W.-L. Ying, H.-S.
Ru, X.-L. Liu, Aquaculture 2011, 318, 235–238.
Amine 41b (85.0 mg, 0.279 mmol, 1.00 equiv.) was dissolved in dry
acetonitrile (80 mL). The crude product was purified by flash
chromatography (cyclohexane/EtOAc = 1:1) and the product ob-
tained as a yellow solid in 48% (33.4 mg, 0.109 mmol) yield.
[4] B. D. Krane, M. O. Fagbule, M. J. Shamma, Nat. Prod. 1984,
47, 1–43.
[5] K. Merz, T. Muller, S. Vanderheiden, G. Eisenbrand, D.
Marko, S. Bräse, Synlett 2006, 3461–3463.
[6] A. M. Linsenmeier, C. M. Williams, S. Bräse, J. Org. Chem.
2011, 76, 9127–9132.
1
Rf = 0.24 (cyclohexane/EtOAc = 1:1), m.p. 131–134 °C. H NMR
(CDCl3, 400 MHz): δ = 9.07 (s, 1 H), 8.35 (d, J = 8.1 Hz, 1 H),
8.13 (d, J = 8.3 Hz, 1 H), 7.87 (s, 1 H), 7.70–7.66 (m, 1 H), 7.63–
7.59 (m, 1 H), 7.30 (s, 1 H), 6.14 (s, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 151.8, 151.4, 148.0, 144.1, 130.2, 130.1, 127.9, 126.6,
[7] a) G. M. Badger, C. P. Joshua, G. E. Lewis, Tetrahedron Lett.
1964, 5, 3711–3713; b) Y. Park, I. Lee, Y. J. Kim, Heterocycl.
Chem. 1994, 31, 1625–1629; c) K. Mizuno, C. Pac, H. Sakurai,
Bull. Chem. Soc. Jpn. 1973, 46, 3316; d) R. Alonso, P. J.
Campos, B. García, M. A. Rodríguez, Org. Lett. 2006, 8, 3521–
3523; e) J. L. Romera, J. M. Cid, A. A. Trabanco, Tetrahedron
Lett. 2004, 45, 8797–8800.
[8] a) M. E. Budén, V. B. Dorn, M. Gamba, A. B. Pierini, R. A.
Rossi, J. Org. Chem. 2010, 75, 2206–2218; b) S. V. Kessar, Y. P.
Gupta, K. Dhingra, G. S. Sharma, S. Narula, Tetrahedron Lett.
1977, 18, 1459–1462.
124.2, 123.0, 121.9, 105.4, 101.9, 99.9 ppm. IR (ATR): ν = 2909
˜
(vw), 2164 (vw), 2079 (vw), 1727 (vw), 1620 (vw), 1581 (vw), 1519
(vw), 1497 (w), 1485 (w), 1461 (m) cm–1. MS (EI): m/z (%) = 223
(100) [M]+, 164 (16), 138 (30). HRMS (EI): calcd. for C14H9NO2
223.0633 [M]+; found 223.0633.
2-Chloro-[1,3]dioxolo[4,5-j]phenanthridine (46): Amine 43 (40.0 mg,
0.117 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (40 mL).
The crude product was purified by flash chromatography (cyclo-
hexane/EtOAc = 1:1) and the product obtained as a yellow solid
in 16% (4.90 mg, 0.0190 mmol) yield. Rf = 0.268(Cy-Hex/EtOAc =
[9] P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH,
Weinheim, Germany, 2004.
[10] J. L. Romera, J. M. Cid, A. A. Trabanco, Tetrahedron Lett.
2004, 45, 8797–8800.
1
[11] C. G. Bochet, Tetrahedron Lett. 2000, 41, 6341–6342.
[12] For selected syntheses in this area, see: a) A. M. Rosa, S. Prab-
hakar, A. M. Lob, Tetrahedron Lett. 1990, 31, 1881–1884; b)
Y.-Y. Liu, R.-J. Song, C.-Y. Wu, L.-B. Gong, M. Hu, Z.-Q.
Wang, Y.-X. Xie, J.-H. Li, Adv. Synth. Catal. 2012, 354, 347–
353; c) M. G. Banwell, D. W. Lupton, X. Ma, J. Renner, M. O.
Sydnes, Org. Lett. 2004, 6, 2741–2744; d) M. E. Budén, V. B.
Dorn, M. Gamba, A. B. Pierini, R. A. Rossi, J. Org. Chem.
2011, 75, 2206–2218.
[13] a) S. Kobayashi, M. Kihara, H. Matsumoto, Yakugaku Zasshi
1978, 98, 863–868; b) S. Kobayashi, M. Kihara, Y. Miyake,
Heterocycles 1985, 23, 159–164; c) S.-C. Lu, X.-X. Zhang, Z.-
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1:1). H NMR (CDCl3, 400 MHz): δ = 9.08 (s, 1 H), 8.11 (d, J =
8.9 Hz, 1 H), 7.83 (s, 1 H), 7.56 (dd, J = 8.9, 2.2 Hz, 1 H), 7.45 (s,
1 H), 7.35 (s, 1 H), 6.21 (s, 2 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 155.5, 151.4, 148.9, 129.1, 124.9, 121.6, 116.7, 116.2,
110.5, 105.7, 102.3, 100.0 ppm; 2 C not detected. IR (ATR): ν =
˜
3246 (w), 3051 (w), 2962 (w), 2911 (w), 2248 (vw), 2077 (vw), 1887
(vw), 1678 (m), 1619 (w), 1596 (m), 1478 (m), 1456 (m) cm–1. MS
(EI): m/z (%) = 257/259 (5/1) [M]+, 168 (9), 153/155 (7/4), 58 (31),
43 (100) [M – C12H5NClO]+. HRMS (EI): calcd. for C14H8NClO2
257.0244 [M]+; found 257.0242.
4-Fluoro-[1,3]dioxolo[4,5-j]phenanthridine (47): Amine 44 (42.0 mg,
0.129 mmol, 1.00 equiv.) was dissolved in dry acetonitrile (40 mL).
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Job/Unit: O30218
/KAP1
Date: 08-05-13 18:18:24
Pages: 11
Photochemical Synthesis of Phenanthridines
[14] a) M. Kihara, S. Kobayashi, Chem. Pharm. Bull. 1978, 26, 155– [17] O. M. Saavedra, WO Patent, WO2007054831, 2007.
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[15] J. Grimshaw, A. P. de Silva, Chem. Soc. Rev. 1981, 10, 181–203.
[16] W. L. F. Armarego, C. L. L. Chai, in: Purification of Labora-
tory Chemicals, Butterworth-Heinemann, London, 2003.
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Org. Lett. 2007, 9, 3683–3685; b) J. Ruiz, A. Ardeo, R. Ignacio,
N. Sotomayor, E. Lete, Tetrahedron 2005, 61, 3311–3324.
Received: February 9, 2013
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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