Regiospecific synthesis of alkylphenanthrenes using a combined directed ortho and remote metalation - Suzuki-Miyaura cross coupling strategy

Article abstract of DOI:10.1139/v03-179

Using a combined directed ortho metalation (DoM) - Suzuki-Miyaura cross coupling - directed remote metalation (DreM) approach, the alkylphenanthrenes (APs) 1-methyl- (5a), 1,7-dimethyl- (5b), 2,7-dimethyl- (Sc), 7-ethyl-1-methyl- (15), and 7-tert-butyl-1-methylphenanthrenes (27) have been synthesized in four to seven steps and 21%-36% overall yields. In contrast to classical protocols, this method, which may be scaled to gram quantities, provides single isomers of APs in high purity of value as analytical standards for environmental studies. Aminocarbonylation of triflates to N,N-diethylbenzamides (9 → 10) and anionic Fries rearrangement (23 → 24) provide other potential links to DoM chemistry.

Full text of DOI:10.1139/v03-179

195
Regiospecific synthesis of alkylphenanthrenes
using a combined directed ortho and remote
metalation – Suzuki–Miyaura cross coupling
strategy1
Xiongwei Cai, Stephen Brown, Peter Hodson, and Victor Snieckus
Abstract: Using a combined directed ortho metalation (DoM) – Suzuki–Miyaura cross coupling – directed remote
metalation (DreM) approach, the alkylphenanthrenes (APs) 1-methyl- (5a), 1,7-dimethyl- (5b), 2,7-dimethyl- (5c), 7-
ethyl-1-methyl- (15), and 7-tert-butyl-1-methylphenanthrenes (27) have been synthesized in four to seven steps and
21%–36% overall yields. In contrast to classical protocols, this method, which may be scaled to gram quantities, pro-
vides single isomers of APs in high purity of value as analytical standards for environmental studies.
Aminocarbonylation of triflates to N,N-diethylbenzamides (9 → 10) and anionic Fries rearrangement (23 → 24) provide
other potential links to DoM chemistry.
Key words: phenanthrene, directed ortho metalation, Suzuki–Miyaura cross coupling, synthesis, polycyclic aromatic hy-
drocarbon, carbonylation.
Résumé : Faisant appel à une approche combinant une métallation orientée en ortho (MOo), un couplage croisé de Su-
zuki et Miyaura et une métallation orientée à distance (MOdi), on a réalisé des synthèses d’alkylphénanthrènes (AP),
les 1-méthyl- (5a), 1,7-diméthyl- (5b), 2,7-diméthyl- (5c), 7-éthyl-1-méthyl- (15) et 7-tert-butyl-1-méthylphénanthrènes
(27), qui impliquaient de quatre à sept étapes avec des rendements globaux allant de 21 % à 36 %. Par opposition avec
les protocoles classiques, cette méthode être réalisée à des échelles du gramme et elle conduit à des isomères uniques
d’AP, de grande pureté qui peuvent être utilisés comme références pour des études environnementales.
L’aminocarbonylation de triflates de N,N-diéthylbenzamides (9 → 10) et le réarrangement anionique de Fries (23 → 24)
fournissent d’autres liens vers la chimie de la MOo.
Mots clés : phénanthrène, métallation orienté en ortho, couplage croisé de Suzuki et Miyaura, hydrocarbure aromatique
polycyclique, carbonylation.
[Traduit par la Rédaction] Cai et al. 205
Introduction
PAH classes, the APs have been sparsely evaluated for tox-
icity effects, arguably because of lack of commercial sources
of analytically pure compounds in sufficient quantity. Only a
few APs are available, e.g., 1-methyl-, 1,7-dimethylphen-
anthrene, and retene at times of uncertain and insufficient
isomer purity and inadequate quantity.3 Among the few
methods of phenanthrene synthesis, classical electrophilic
substitution (5), Pschorr reaction (6), ring expansion (7),
Mallory photocyclization (8), and recently, palladium-
catalyzed trimerization (9) and radical cyclization (10), tac-
tics have, to various degrees, been applied to AP preparation
but suffer in length or produce mixtures of isomers. We re-
port a combined metalation – Suzuki–Miyaura cross cou-
Alkylphenanthrenes (APs) represent a significant class of
polycyclic aromatic hydrocarbons (PAHs) found in soil, sed-
iment, and other aquatic sites, which constitute environmen-
tal pollutants with substantial levels of toxicity towards
marine diatoms, gastropods, mussels, crustaceans, and espe-
cially fish (1–3). The key biological marker for toxicity,
retene (7-isopropyl-1-methylphenanthrene) causes reductions
in recruitment and growth and an increased prevalence of
morphological abnormalities of laval pink salmon and Pa-
cific herring (3, 4), effects which were observed in the 1989
Exxon Valdez oil spill in Alaska (1). Among the various
Received 29 July 2003. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 12 January 2004.
This manuscript is dedicated to Ed Piers for placing Canadian synthetic organic chemistry on the international map.
X. Cai, S. Brown, and V. Snieckus.2 Department of Chemistry, Queen’s University, Kingston, ON K7L 3N6, Canada.
Peter Hodson. School of Environmental Studies, Queen’s University, Kingston ON K7L 3N6, Canada.
1This article is part of a Special Issue dedicated to Professor Ed Piers.
2Corresponding author (e-mail: snieckus@chem.queensu.ca).
31,7-Dimethylphenanthrene and retene available from Chiron AS, Stiklestadveien 1, Trondheim, N-7041, Norway;
1-methylphenanthrene available from Absolute Standards, Inc., Hamdan, Conn. 06518, U.S.A.
Can. J. Chem. 82: 195–205 (2004)
doi: 10.1139/V03-179
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Scheme 1.
pling methodology involving both directed ortho (DoM) and
remote metalation (DreM) reactions, 1 + 2 → 3 → 4 → 5
(Scheme 1) that provides short, efficient, and regioselective
routes to APs 5a, 5c, 15, and 27. This general strategy pro-
vides the phenanthrene class of PAHs as single isomers in
preparative quantities and contrasts with classical methods,
which invariably involve harsh conditions, lack of regio-
selectivity, and considerable handling of potentially toxic
materials (11). Recently, de Koning et al. has reported a
general phenanthrene synthesis using t-BuOK-mediated
cyclization of esters corresponding to 3 (12).
phenanthrols 4a–4c were then converted into their triflates
7a–7c (15), which upon Pd-catalyzed hydrogenolysis in the
presence of formic acid, afforded 1-methyl-phenanthrene
(5a), 1,7-dimethylphenanthrene (5b), and 2,7-dimethylphen-
anthrene (5c) in modest to excellent yields. Overall yields
(5a (29%), 5b (27%), 5c (45%), in four to six steps from
commercial materials) cannot be compared with previous
routes for lack of data with the exception of 6a, which was
obtained by Pschorr synthesis in 21% overall yield and four
steps (16).
Synthesis of 7-ethyl-1-methylphenanthrene (15)
Synthesis of 1-methyl- (5a), 1,7-dimethyl- (5b), and 2,7-
dimethyl- (5c) phenanthrenes
The synthesis of the homologous 7-ethyl-1-methyl-
phanthrene (15) commenced from 3-ethylbenzamide (10),
which was obtained by a aminocarbonylation protocol
(Scheme 3). Thus, commercial 3-ethylphenol (8) was con-
verted into the corresponding triflate 9 (15), which was sub-
jected to aminocarbonylation conditions (17) using a number
of phosphine ligands that included PPh3, dppf, and dppp. In
the case of PPh3, rapid black precipitation was observed and
the product 10 was obtained in low yield with the material
balance being recovered starting material (72%). In contrast,
the bidentate ligands dppp and dppf behaved well, leading to
similar yields of 10 and completion of reactions with only
trace amounts of starting material being detected by GC at
the conclusion of the reaction. In this two-phase reaction, it
is imperative to ensure good mixing, especially when the re-
action is carried out on a large scale. Thus, using a balloon
of CO led to poorer yields and longer completion times
compared to bubbling CO into the solution for the duration
of the reaction.
Metalation of 3-ethylbenzamide 10 (Scheme 4) under the
low-temperature conditions used previously for 6b
(Scheme 2) followed by boronation and treatment with
pinacol paralleled the reaction of 6b in that it led to the for-
mation of boronate 11, the product of exclusive C-6 deproto-
nation. The isolated and purified boronate 11 was subjected
to Suzuki–Miyaura cross coupling with 3-bromo-o-xylene
under the previously defined conditions to afford the biaryl
amide 12, which, upon treatment with LDA, led cleanly to
the 9-phenanthrol 13. Analogous to the 4 → 7 reactions,
The synthesis of 1-methylphenanthrene (5a) (Scheme 2)
was initiated from N,N-diethylbenzamide (6a) that upon
metalation under standard conditions (s-BuLi / TMEDA /
–78 °C / THF / 1 h) followed by quenching with trimethyl
borate and acidic workup afforded the boronic acid 2a.
Without purification, 2a was subjected, as the reactant in ex-
cess (1.4 equiv.), to the Suzuki–Miyaura cross coupling re-
action with the commercially available 3-bromo-o-xylene to
give the biaryl amide 3a in good yield. Metalation–
boronation of 6b, the insecticide DEET® (13), at –98 °C
proceeded smoothly to give the corresponding boronic acid,
which was isolated and purified as the pinacol boronate 2b.
NMR analysis provided structural confirmation that DoM of
6b occurred exclusively on C-6, a result differing with Beak
and Brown’s observation that metalation of 6b under similar
conditions but using MeOD quench yields C-6 and C-2
deuterated products in the ratio of 2:1 (Scheme 2) (14). The
observed difference in regioselectivity using trimethyl borate
as the electrophile may be due to its greater size. Boronate
2b was subjected to Suzuki–Miyaura cross coupling with 3-
bromo-o-xylene and 4-bromo-m-xylene to give biaryls 3b
and 3c, respectively, in satisfactory yields.
Application of the standard DreM conditions (11a) to the
biaryl amides 3a–3c (2.5 equiv. of LDA / THF / 0 °C) re-
sulted in smooth cyclization to the 9-phenanthrols 4a–4c,
which underwent oxidation slowly and changed colors in the
air but were stable in sealed vials at –30 °C. The 9-
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Cai et al.
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Scheme 2. Reagents and conditions: (a) (i) s-BuLi / TMEDA / THF / –78 °C; (ii) B(OMe)3 / –78 °C; (iii) aq. NH4Cl; (b) (i) s-BuLi /
TMEDA / THF / –98 °C; (ii) B(OMe)3 / –98 °C; (iii) aq. NH4Cl; (iv) pinacol / MgSO4 / CH2Cl2/ 0 °C; (c) Pd(PPh3)4 / DME /
Na2CO3 / 6-bromo-o-xylene / reflux / 4 h; (d) Pd(PPh3)4 / DME / Na2CO3 / 6-bromo-m-xylene / reflux/ 4 h; (e) (i) LDA / THF /
0 °C; (ii) aq. NH4Cl; (f) 2,6-lutidine / Tf2O / CH2Cl2 / 30 min; (g) Pd(OAc)2 / PPh3 / Et3N / HCO2H / DMF / 60 °C / 20 min.
conversion of 13 into its triflate 14 followed by Pd-catalyzed
hydrogenolysis by the agency of formic acid furnished 15 in
high yield and >98% purity (HPLC analysis). This con-
cluded the synthesis of 7-ethyl-1-methylphenthrene (15) in
six steps in an overall yield of 36%.
bidentate phosphine ligands for the reaction 17 → 18, as in-
dicated in tabular form, gave unsatisfactory results.
Therefore, a strategy involving the inversion of coupling
partners in the Suzuki–Miyaura reaction 20 + 21 → 19 was
pursued (Scheme 7). Thus, 4-tert-butylphenol 22 (Scheme 5)
was quantitatively converted into the O-carbamate 23 that
was subjected to conditions (s-BuLi / TMEDA / –78 °C) for
the anionic Fries rearrangement (18) to give the salicylamide
24 in good yield. Conversion of 24 into triflate 20 using 2,6-
lutidine proceeded in low yield (20%) compared to that
achieved for previously prepared triflates. However, using
pyridine as catalyst, 20 was obtained in good yield. In the
key step, triflate 20 underwent Suzuki–Miyaura cross cou-
Synthesis of 7-tert-butyl-1-methylphenanthrene (27)
In pursuit of the same strategy (Scheme 3) for the synthe-
sis of 7-tert-butyl-1-methyl-phenanthrene (27, Scheme 5),
we envisaged the preparation of the requisite benzamide 18
by the amidocarbonylation of 17, which, in turn, was avail-
able in high yield from the commercial phenol 16
(Scheme 6). However, modest exploration of conditions and
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Scheme 3.
Scheme 4. Reagents and conditions: (a) (i) s-BuLi / TMEDA / THF / –98 °C; (ii) B(OMe)3 / –98 °C, (iii) aq. NH4Cl; (iv) pinacol /
MgSO4 / CH2Cl2 / 0 °C; (b) Pd(PPh3)4 / DME / Na2CO3 / 6-bromo-o-xylene / reflux / 4 h; (c) (i) LDA / THF / 0 °C; (ii) aq. NH4Cl;
(d) 2,6-lutidine / Tf2O / CH2Cl2 / 30 min; (e) Pd(OAc)2 / PPh3 / Et3N / HCO2H / DMF / 60 °C / 20 min.
pling with the commercial boronic acid 21, to form the
biaryl amide 19 in very good yield. As before, LDA-
mediated cyclization furnished, in excellent yield, the 9-
phenanthrol 25 that was converted into its triflate 26 and
thence into the target 7-tert-butyl-1-methylphenanthrene 27.
Thus, the synthesis of 27 was accomplished in seven steps in
an overall yield of 21%.
thesized by a combined DoM – Suzuki–Miyaura cross cou-
pling – DreM methodology in overall yields of 29% (five
steps), 27% (five steps), 45% (five steps), 36% (six steps),
and 21% (seven steps), respectively. A general and effective
methodology has been thereby provided that allows antici-
pated application for the synthesis of various APs as single
isomers in high purity and in scales ranging from 1 to 4 g.
As an adjunct, a representative aminocarbonylation method
of readily available aryl triflates to N,N-diethylbenzamides
has been briefly investigated (Scheme 3) based on which a
further general link to DoM chemistry may be anticipated.
Conclusion
This work constitutes a contribution for the convenient
and efficient preparation of the phenanthrene class of PAHs
that contrasts with classical methods in terms of
regioselectivity, brevity, mildness of conditions, and neces-
sity for considerable handling of potentially toxic materials.
Thus, the alkylphenanthrenes (APs) 1-methyl- (5a), 1,7-
dimethyl- (5b), 2,7-dimethyl- (5c), 7-ethyl-1-methyl- (15),
and 7-tert-butyl-1-methyl (27) phenanthrenes have been syn-
Experimental section
General methods
Melting points are uncorrected. IR spectra were recorded
neat or as KBr discs using a BOMEM FT-IR spectrometer.
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Cai et al.
199
Scheme 5. Reagents and conditions: (a) (i) NaH / THF / 0 °C; (ii) ClCONEt2; (b) (i) s-BuLi / TMEDA / THF / –78 °C to rt; (ii) aq.
NH4Cl; (c) Tf2O / pyridine / CH2Cl2; (d) Pd(PPh3)4 / DME, Na2CO3 / 21 / reflux / 4 h; (e) LDA / THF / 0 °C; (ii) aq NH4Cl; (f) 2,6-
lutidine / Tf2O / CH2Cl2 / 30 min; (g) Pd(OAc)2 / PPh3 / Et3N / HCO2H / DMF / 60 °C / 20 min.
Scheme 6.
Scheme 7.
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1H (300 MHz) and 13C (75.43 MHz) NMR spectra were ob-
tained in CDCl3 using either TMS (for H) or CDCl3 (for
D. Synthesis of triflates
1
A solution of the phenanthrol (1.00 mmol) and 2,6-
lutidine or pyridine (1.2 mmol) in CH2Cl2 (10 mL) was
stirred for 5 min at 0 °C followed by the addition of triflic
anhydride (1.20 mmol). The resulting mixture was stirred at
rt for 30 min and water was added (5 mL). The aqueous
layer was separated and extracted with CH2Cl2 (3 × 10 mL).
The combined extract was dried (Na2SO4) and concentrated
in vacuo. The residue was purified by flash column chroma-
tography (EtOAc–hexane) to afford the product.
13C) as the internal standard on a Bruker Avance-300 spec-
trometer. THF was freshly distilled from sodium benzophe-
none ketyl under nitrogen and CH2Cl2 and HN-i-Pr2 were
freshly distilled from CaH2 under nitrogen. n-Butyllithium
and s-butyllithium were purchased from Aldrich as solutions
in hexanes, stored in resealable containers, and titrated peri-
odically against s-butanol using 1,10-phenanthroline as the
indicator (19). N,N-Diethyl benzamide (6a) was prepared
from benzoyl chloride (20). N,N-Diethyl toluamide (DEET®)
(6b), 6-bromo-o-xylene, 6-bromo-m-xylene, and 2,3-
dimethylphenylboronic acid (21) were purchased from
Aldrich Chemical Co. All experiments were carried out un-
der argon in dried glassware, using syringe-septum cap tech-
niques. The –78 °C and 0 °C external bath temperatures
designated are approximate as achieved by a dry ice–acetone
or ice–salt baths, respectively. Flash column chromatogra-
phy was carried out using Merck Kieselgel 60 silica gel
(particle size 32–63) with different ratios of EtOAc–hexane
as eluents.
2-(N,N-Diethylcarboxamido)phenylboronic acid (2a)
According to general procedure A, a solution of N,N-
diethylbenzamide (1.77 g, 10.0 mmol), s-BuLi (9.60 mL of a
1.25 mol L–1 solution, 12.0 mmol), and TMEDA (1.07 mL,
1.39 g, 12.0 mmol) was treated with B(OMe)3 (2.73 mL,
2.50 g, 24.0 mmol). Normal workup afforded 2.03 g (92%)
of product as a viscous oil that was used in the cross cou-
pling reactions without further purification.
N,N-Diethyl 2′,3′-dimethyldiphenyl-2-carboxamide (3a)
According to general procedure B, 1-bromo-2,3-
dimethylbenzene (1.36 mL, 1.85 g, 10.0 mmol) was sub-
jected to reaction with 2-(N,N-diethylcarboxamido)phenyl-
boronic acid (3.09 g, 14 mmol) in the presence of Pd(PPh3)4
(0.185 g, 0.16 mmol). Normal workup followed by flash
chromatography (EtOAc–hexanes, 1:5) afforded 2.30 g
(82%) of 3a as colorless crystals, mp 68 to 69 °C (EtOAc).
General procedures
A. Lithiation of benzamides
A solution of the benzamide (1.00 mmol) in anhyd THF
(2 mL) was added dropwise to a stirred solution of s-BuLi–
TMEDA (1:1, 1.20 mmol) complex in anhyd THF (3 mL) at
–78 °C. The resulting mixture was stirred at –78 °C for 1 h,
treated with an excess of B(OMe)3 (2.40 mmol), and the
mixture was warmed to ambient temperature over 8–12 h
and quenched with a satd. aq. NH4Cl solution (5 mL). The
aqueous portion was extracted with Et2O (3 × 5 mL), and
the extract was dried (Na2SO4) and concentrated in vacuo.
The residue was purified by flash column chromatography
(EtOAc–hexanes) to afford the product.
1
IR (KBr) (cm–1): 1632. H NMR (300 MHz, CDCl3) δ: 0.59
(br s, 3H), 0.80 (br s, 3H), 2.01 (s, 3H), 2.19 (s, 3H), 2.40–
3.30 (br m, 3H), 3.65 (br s, 1H), 6.90–7.15 (m, 4H), 7.25 (s,
3H). 13C NMR (75 MHz, CDCl3) δ: 12.1, 14.0, 17.5, 20.9,
38.2, 42.8, 117.3, 118.9, 124.9, 127.5, 127.9, 128.6, 129.5,
130.1, 131.2, 135.0, 137.1, 137.6, 170.3. EI-MS m/z (rel.
int.): 281 (M+, 100), 209 (20), 181 (13), 165 (47), 74 (30).
HR-MS m/z calcd. for C19H23NO: 281.1780; found:
281.1776.
B. Cross coupling reaction of arylboronic acids with
aryl halides and aryl triflates
1-Methyl-9-phenanthrol (4a)
According to general procedure C, treatment of a solution
of N,N-diethyl 2′,3′-dimethylbiphenyl-2-carboxamide (2.81 g,
10 mmol) in THF (20 mL) with a solution of LDA
(25.0 mmol) in THF (80 mL) followed by acidification, nor-
mal workup, and flash chromatography (hexane) afforded
1.98 g (95%) of 4a as colorless crystals, mp 194–197 °C
(CH2Cl2) (lit. (21) mp 199.5–200.5 °C (benzene)). IR (KBr)
A mixture of Pd(PPh3)4 (0.04 mmol) and aryl halide or
aryl triflate (1 mmol) in DME (3 mL) was stirred at room
temperature (rt) for 10 min. The solution of aryl boronic
acid (1.4 mmol) in a minimum amount of ethanol (1 mL)
and DME (2 mL) mixture was added, followed by the addi-
tion of 2 mol L–1 aq. Na2CO3 solution (3 mL). The resulting
mixture was heated at reflux for 12 h, cooled to rt, and ex-
tracted with Et2O (3 × 5 mL). The organic extract was dried
(Na2SO4) and concentrated in vacuo. The residue was puri-
fied by flash column chromatography (EtOAc–hexanes) to
afford the product.
1
(cm–1): 3307. H NMR (300 MHz, DMSO-d6) δ: 2.61 (s,
3H), 7.34 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 6.8 Hz, 1H), 7.61–
7.72 (m, 2H), 8.31 (d, J = 7.4 Hz, 1H), 8.53 (d, J = 7.8 Hz,
1H), 8.77 (d, J = 7.6 Hz, 1H), 10.39 (s, 1H). 13C NMR
(75 MHz, DMSO-d6) δ: 20.5, 102.3, 121.7, 123.3, 123.9,
126.1, 128.0, 128.7, 132.2, 132.6, 132.9, 151.9. EI-MS m/z
(rel. int.): 208 (M+, 100), 178 (17), 165 (38), 152 (5), 89 (5),
76 (5).
C. Synthesis of 9-phenanthrols
To a solution of LDA (2.50 mmol) in THF (8 mL) was
added
a
solution of 2′-methyldiphenyl-2-carboxamide
(1.00 mmol) in THF (2 mL) at 0 °C. The resulting mixture
was stirred at rt for 30 min and quenched with a satd. aq.
NH4Cl solution (5 mL). The aqueous portion was extracted
with Et2O (3 × 5 mL) and the extract was dried (Na2SO4)
and concentrated in vacuo. The residue was purified by flash
column chromatography (EtOAc–hexanes) to afford the
product.
1-Methylphenanthryl-9 trifluoromethanesulfonate (7a)
According to general procedure D, to a solution of 1-
methyl-9-phenanthrol (4a) (1.04 g, 5.00 mmol) and 2,6-
lutidine (0.69 mL, 0.64 g, 6.00 mmol) in CH2Cl2 was added
triflic anhydride (1.01 mL, 1.69 g, 6.00 mmol). Normal
workup followed by flash chromatography (hexane) afforded
1.62 g (95%) of 7a as colorless crystals, mp 60 to 61 °C
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Cai et al.
201
(EtOAc). IR (KBr) (cm–1): 1416, 1206, 1139. 1H NMR
(300 MHz, CDCl3) δ: 2.72 (s, 3H), 7.49 (s, 1H), 7.57 (t, J =
7.2 Hz, 1H), 7.71–7.77 (m, 2H), 7.91 (s, 1H), 8.15–8.21 (m,
1H), 8.47 (d, J = 6.9 Hz, 1H), 8.63–8.68 (m, 1H). 13C NMR
(75 MHz, CDCl3) δ: 20.0, 114.8, 119.5 (q, J = 323 Hz),
121.2, 121.9, 123.7, 125.4, 127.8, 128.0, 129.1, 129.8,
130.1, 132.6, 135.8, 144.7. EI-MS m/z (rel. int.): 340 (M+,
55), 207 (49), 179 (100), 152 (5), 69 (8). HR-MS m/z calcd.
for C16H11F3O3S: 340.0381; found: 340.0387.
CDCl3) δ: 0.65 (br, 3H), 0.75–1.00 (br, 3H), 2.28 (s, 3H),
2.48 (s, 3H), 2.50–3.30 (br, 4H), 3.65–3.85 (s, 1H), 6.98–
7.23 (m, 6H).13C NMR (75 MHz, CDCl3) δ: 12.0, 13.9, 17.4,
20.8, 21.3, 38.0, 42.7, 124.7, 127.4, 129.2, 130.0, 130.9,
131.6, 136.9, 137.1, 170.4. EI-MS m/z (rel. int.): 295 (M+,
35), 222 (100), 177 (48), 180 (57), 165 (65), 74 (47). HR-
MS m/z calcd. for C20H25NO: 295.1936; found: 295.1932.
1,7-Dimethyl-9-phenanthrol (4b)
According to general procedure C, treatment of a solution
of 3b (2.95 g, 10 mmol) in THF (20 mL) with a solution of
LDA (25.0 mmol) in THF (80 mL) for 30 min followed by
acidification, normal workup, and flash chromatography
(hexane) afforded 1.78 g (80%) of 4b as colorless crystals,
1-Methylphenanthrene (5a)
A stirred mixture of 1-methylphenanthryl-9 trifluoro-
methanesulfonate (7a) (0.340 g, 1.00 mmol), Pd(OAc)2
(4.5 mg, 0.02 mmol), PPh3, (10.5 mg, 0.04 mmol), Et3N
(0.303 g, 3.00 mmol), and HCO2H (0.08 mL, 92 mg,
2.00 mmol) in DMF (10 mL) was heated at 60–70 °C for
30 min. The reaction mixture was cooled to rt, water was
added, and the mixture was extracted with Et2O. The com-
bined organic layer was dried (Na2SO4), concentrated to dry-
ness, and the residue was subjected to flash chromatography
(hexane) to afford 96 mg (50%) of 6a as colorless crystals,
mp 118 to119 °C (hexane) (lit. (22) mp 120 to 121 °C (etha-
nol)). IR (KBr) (cm–1): 1598. 1H NMR (300 MHz, CDCl3) δ:
2.87 (s, 3H), 7.56 (d, J = 7.2 Hz, 1H), 7.63–7.69 (m, 3H),
7.88 (d, J = 9.2 Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 8.04 (t,
J = 9.2 Hz, 1H), 8.69 (d, J = 8.1 Hz, 1H), 8.81 (d, J =
8.1 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ: 20.5, 121.4,
123.4, 123.5, 126.7, 127.1, 127.2, 128.3, 129.0, 130.9,
131.3, 132.2, 135.4. EI-MS m/z (rel. int.): 192 (M+, 100),
165 (23), 150 (4), 139 (4), 95 (28), 83 (24).
1
mp 203–205 °C (CH2Cl2). IR (KBr) (cm–1): 3351. H NMR
(300 MHz, CDCl3) δ: 2.54 (s, 3H), 2.59 (s, 3H), 7.20 (s,
1H), 7.30–7.39 (m, 2H), 7.51 (d, J = 9.0 Hz, 1H), 8.07 (s,
1H), 8.49 (d, J = 9.0 Hz, 1H), 8.65 (d, J = 9.0 Hz, 1H),
10.30 (s, 1H). 13C NMR (75 MHz, DMSO-d6) δ: 20.9, 22.4,
102.5, 121.8, 123.1, 124.0, 124.2, 126.4, 126.8, 128.6,
129.9, 130.4, 132.4, 133.0, 136.6, 151.9. EI-MS m/z (rel.
int.): 222 (M+, 100), 207 (7), 194 (13), 179 (41), 110 (3), 89
(3). HR-MS m/z calcd. for C16H14O: 222.1045; found:
222.1040.
1,7-Dimethylphenanthryl-9-trifluoromethanesulfonate (7b)
According to general procedure D, a solution of 4b
(1.11 g, 5.00 mmol) and 2,6-lutidine (0.69 mL, 0.64 g,
6.00 mmol) in CH2Cl2 was treated with triflic anhydride
(1.01 mL, 1.69 g, 6.00 mmol). Normal workup followed by
flash chromatography (hexane) afforded 1.42 (90%) g of 7b
as colorless crystals, mp 74 to 75 °C (EtOAc). IR (KBr)
Pinacolo[2-(N,N-diethylcarboxamido)-4-methylphenyl]bor-
onate (2b)
1
(cm–1): 1421, 1215, 1140. H NMR (300 MHz, CDCl3) δ:
According to general procedure A, a solution of N,N-di-
ethyl-3-methylbenzamide (1.91 g, 10.0 mmol), s-BuLi
(9.60 mL of a 1.25 mol L–1 solution,12.0 mmol), and
TMEDA (1.07 mL, 1.39 g, 12.0 mmol) was treated with
B(OMe)3 (2.73 mL, 2.50 g, 24.0 mmol). Normal workup af-
forded a thick oil that was stirred with pinacol (2.83 g,
24.0 mmol) and MgSO4 in dry CH2Cl2 for 12 h. Filtration
and concentration of the filtrate gave a residue that was puri-
fied by flash chromatography (EtOAc–hexanes, 1:3) to af-
ford 2.21 g (70%) of 2b as a colorless oil. IR (neat) (cm–1):
2.64 (s, 3H), 2.75 (s, 3H), 7.49 (d, J = 7.2 Hz, 1H), 7.57–
7.64 (m, 2H), 7.72 (s, 1H), 7.74 (s, 1H), 8.53 (d, J = 8.4 Hz,
1H), 8.63 (d, J = 8.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ:
20.4, 22.5, 115.0, 119.5 (q, J = 315 Hz), 121.4, 121.7, 123.9,
125.8, 128.0, 128.9, 129.8, 130.6, 130.8, 136.0, 138.4,
144.9. EI-MS m/z (rel. int.): 354 (M+, 38), 221 (39), 193
(100), 178 (20), 69 (7). H-MS m/z calcd. for C17H13O3F3S:
354.0538; found: 354.0545.
1,7-Dimethylphenanthrene (5b)
1
A stirred mixture of 7b (0.354 g, 1.00 mmol), Pd(OAc)2
(4.5 mg, 0.02 mmol), PPh3 (10.5 mg, 0.04 mmol), Et3N
(0.303 g, 3.00 mmol), and HCO2H (0.08 mL, 92 mg,
2.00 mmol) in DMF (10 mL) was heated at 60–70 °C for
30 min, cooled to rt, and treated with water (10 mL). The re-
sulting aqueous solution was extracted with Et2O (3 ×
10 mL), the combined organic extract was dried (Na2SO4)
and concentrated in vacuo, and the residue was subjected to
flash chromatography (hexane) to afford 175 mg (85%) of
5b as colorless crystals, mp 83 to 84 °C (hexane) (lit. (23)
1633, 1432, 1350. H NMR (300 MHz, CDCl3) δ: 0.88 (t,
J = 7.2 Hz, 3H), 1.15 (s, 12H), 1.20 (t, J = 7.2 Hz, 3H), 2.20
(s, 3H), 3.02 (q, J = 7.2 Hz, 2H), 3.41 (q, J = 7.2 Hz, 2H),
6.90 (s, 1H), 7.02 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 8.1 Hz,
1H). 13C NMR (75 MHz, CDCl3) δ: 14.2, 14.4, 22.3, 25.5,
38.8, 43.6, 84.2, 123.1, 126.8, 129.2, 136.2, 141.7, 144.1,
172.5. EI-MS m/z (rel. int.): 316 (M+ – H, 25), 302 (13), 259
(100), 218 (18), 174 (18), 144 (18), 177 (18), 83 (7), 55 (4).
HR-MS m/z calcd. for C18H27BNO3 (M+ – H): 316.2084;
found: 316.2093.
1
mp 86 °C (ethanol)). H NMR (300 MHz, CDCl3) δ: 2.59 (s,
N,N-Diethyl 3,2′,3′-trimethyldiphenyl-2-carboxamide (3b)
According to general procedure B, 1-bromo-2,3-
dimethylbenzene (1.36 mL, 1.85 g, 10.0 mmol) was sub-
jected to reaction with 2b (3.16 g, 10 mmol) in the presence
of Pd(PPh3)4 (0.185 g, 0.16 mmol). Normal workup fol-
lowed by flash chromatography (EtOAc–hexane, 1:5) af-
forded 1.89 g (64%) of 3b as colorless crystals, mp 66–
3H), 2.78 (s, 3H), 7.43–7.58 (m, 3H), 7.71 (s, 1H), 7.75 (d,
J = 9.1 Hz, 2H), 7.90 (d, J = 9.1 Hz, 1H), 8.70 (d, J =
8.4 Hz, 1H), 8.62 (d, J = 8.4 Hz, 1H). 13C NMR (75 MHz,
CDCl3) δ: 20.4, 21.9, 121.2, 123.4, 126.5, 126.9, 127.8,
128.8, 129.0, 130.9, 131.0, 132.3, 135.3, 136.6. EI-MS m/z
(rel. int.): 206 (M+, 100), 192 (18), 179 96), 166 (6), 152 (5),
102 (6), 88 (5). HR-MS m/z calcd. for C16H14: 206.1096;
found: 206.1090.
1
68 °C (EtOAc). IR (KBr) (cm–1): 1630. H NMR (300 MHz,
© 2004 NRC Canada

202
Can. J. Chem. Vol. 82, 2004
(dd, J = 8.5, 1.5 Hz, 2H), 7.69 (s, 2H), 7.70 (s, 2H), 8.58 (d,
J = 8.5 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 21.9,
122.8, 127.1, 128.5, 128.6, 128.7, 132.3, 136.2. EI-MS m/z
(rel. int.): 206 (100), 191 (46), 189 (47), 178 (19), 69 (20).
N,N-Diethyl 4,2′,4′-trimethyldiphenyl-2-carboxamide (3c)
According to general procedure B, 1-bromo-2,4-
dimethylbenzene (0.27 mL, 0.37 g, 2.0 mmol) was subjected
to reaction with pinacolo[2-(N,N-diethylcarboxamido)-4-
methylphenyl]boronate (2b) (0.63 g, 2.0 mmol) in the pres-
ence of Pd(PPh3)4 (37 mg, 0.032 mmol). Normal workup
followed by flash chromatography (EtOAc–hexane, 1:5) af-
forded 0.38 g (80%) of 3c as a colorless oil. IR (neat) (cm–1)
3-Ethylphenyltrifluoromethanesulfonate (9)
According to method D, a solution of 3-ethylphenol (8)
(1.22 g, 10.00 mmol) and 2,6-lutidine (1.40 mL, 1.28 g,
12.00 mmol) in CH2Cl2 (100 mL) was treated with triflic an-
hydride (2.01 mL, 3.38 g, 12.00 mmol). Normal workup fol-
lowed by flash chromatography (hexane) afforded 2.28 g
(90%) of 9 as a colorless oil. IR (neat) (cm–1): 1424, 1214,
1
1633. H NMR (300 MHz, CDCl3) δ: 0.60–0.90 (m, 6H),
2.20 (s, 3H), 2.32 (s, 3H), 2.40 (s, 3H), 2.50–3.90 (br, 4H),
6.90–7.30 (m, 6H). 13C NMR (75 MHz, CDCl3) δ: 20.6,
21.5, 21.5, 126.2, 128.1, 128.6, 129.3, 130.1, 130.7, 131.2,
135.0, 135.1, 137.3, 137.4, 137.6, 170.8. EI-MS m/z (rel.
int.): 294 (18), 265 (64), 74 (70). HR-MS m/z calcd. for
C20H25NO: 295.1936; found: 295.1930.
1
1143. H NMR (300 MHz, CDCl3) δ: 1.29 (t, J = 8.4 Hz,
3H), 2.73 (q, J = 8.4 Hz, 2H), 7.14 (s, 1H), 7.19–7.34 (m,
2H), 7.38 (t, J = 15.0 Hz, 1H). 13C NMR (75 MHz, CDCl3)
δ: 15.4, 28.9, 118.8, 119.2 (q, J = 315 Hz), 121.0, 129.4,
130.4, 147.6, 150.1. EI-MS m/z (rel. int.): 254 (M+, 100),
174 (75), 121 (47), 91 (90), 77 (22), 65 (8), which showed
2,7-Dimethyl-9-phenanthrol (4c)
According to general procedure C, treatment of a solution
of (3c) (0.30 g, 1.0 mmol) in THF (10 mL) with a solution
of LDA (2.5 mmol) in THF (10 mL) for 30 min followed by
acidification, normal workup, and flash chromatography
(hexane) afforded 0.21 g (94%) of 4c as colorless crystals,
1
identical H NMR, 13C NMR, and MS spectra to those re-
ported for authentic material (26).
N,N-Diethyl 3-ethylbenzamide (10)
1
mp 154 to 155 °C (CH2Cl2). IR (KBr) (cm–1): 3545. H
A stirred mixture of 9 (0.254 g, 1.00 mmol), Pd(OAc)2
(6.7 mg, 0.03 mmol), dppf (33 mg, 0.06 mmol), Et3N
(0.42 mL, 0.303 g, 2.00 mmol), and Et2NH (2.06 mL,
1.46 g, 20.0 mmol) in DMF (10 mL) was heated at 60–70 °C
for 12 h, cooled to rt, and treated with water (10 mL). The
aqueous portion was extracted with Et2O (3 × 10 mL) and
the extract was dried (Na2SO4) and concentrated in vacuo.
The residue was purified by flash column chromatography
(EtOAc–hexane, 1:5) to afford 0.140 g (70%) of 10 as a yel-
low oil. IR (neat) (cm–1): 1633. 1H NMR (300 MHz, CDCl3)
δ: 1.00–1.20 (br, 6H), 1.17 (t, J = 7.2 Hz, 3H), 2.60 (q, J =
7.2 Hz, 2H), 3.17 (br s, 2H), 3.48 (br s, 2H), 7.08–7.27 (m,
4H). 13C NMR (75 MHz, CDCl3) δ: 13.2, 14.6, 15.7, 29.1,
39.5, 43.6, 123.7, 126.7, 128.9, 137.6, 144.7, 171.8. EI-MS
m/z (rel. int.): 205 (M+, 58), 176 (7), 133 (100), 105 (28), 77
(17). HR-MS m/z calcd. for C13H19NO: 205.1467; found:
205.1469.
NMR (500 MHz, CDCl3) δ: 2.46 (s, 3H), 2.53 (s, 3H), 7.00
(s, 1H), 7.25 (dd, J = 8.5, 1.5 Hz, 1H), 7.49 (dd, J = 8.5,
1.5 Hz, 1H), 7.50 (s, 1H), 8.05 (s, 1H), 8.48 (d, J = 8.5 Hz,
1H), 8.58 (d, J = 8.5 Hz, 1H), 10.21 (s, 1H). 13C NMR
(125 MHz, DMSO-d6) δ: 22.0, 22.1, 105.5, 122.9, 123.2,
124.2, 126.0, 126.7, 126.8, 129.5, 129.8, 133.6, 135.9,
136.5, 151.5. EI-MS m/z (rel. int.): 223 (100), 208 (30). HR-
MS m/z calcd. for C16H14O: 222.1045; found: 222.1039.
2,7-Dimethylphenanthryl-9 trifluoromethanesulfonate (7c)
According to general procedure D, a solution of 4c
(0.11 g, 0.50 mmol) and 2,6-lutidine (0.07 mL, 0.064 g,
0.60 mmol) in CH2Cl2 was treated with triflic anhydride
(0.10 mL, 0.17 g, 0.60 mmol). Normal workup followed by
flash chromatography (hexane) afforded 0.17 g (95%) of 7c
as colorless crystals, mp 138 to 139 °C (hexane). IR (KBr)
1
(cm–1): 1430. H NMR (500 MHz, CDCl3) δ: 2.58 (s, 3H),
2.63 (s, 3H), 7.53 (dd, J = 8.5, 1.0 Hz, 1H), 7.58 (dd, J =
8.5, 1.0 Hz, 1H), 7.66 (s, 1H), 7.68 (s, 1H), 7.92 (s, 1H),
8.51 (J = 8.0 Hz, 1H), 8.56 (d, J = 8.0 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ: 21.8, 22.2, 118.0, 119.2 (q, J =
318 Hz), 121.5, 122.9, 123.2, 125.5, 127.9, 128.9, 130.0,
130.3, 130.6, 137.6, 137.8, 144.71. EI-MS m/z (rel. int.):
354 (5), 221 (22), 193 (100), 178 (25), 69 (24). HR-MS m/z
calcd. for C17H13O3F3S: 354.0538; found: 354.0540.
Pinacolo[2-(N,N-diethylcarboxamido)-3-ethylphenyl]bor-
onate (11)
According to general procedure A, a solution of 10
(2.05 g, 10.0 mmol), s-BuLi (9.60 mL of a 1.25 mol L–1 so-
lution, 12.0 mmol), and TMEDA (1.07 mL, 1.39 g,
12.0 mmol) was treated with B(OMe)3 (2.73 mL, 2.50 g,
24.0 mmol). Normal workup afforded a thick oil that was
stirred with a solution of pinacol (2.83 g, 24.0 mmol) and
anhyd MgSO4 (5 g) in dry CH2Cl2 (20 mL). Filtration fol-
lowed by concentration gave a residue that was purified by
flash chromatography (EtOAc–hexane, 1:3) to afford 2.51 g
(76%) of 11 as a colorless oil. IR (neat) (cm–1): 1635, 1432,
2,7-Dimethylphenanthrene (5c)
A stirred mixture of 7c (0.035 g, 0.10 mmol), Pd(OAc)2
(0.5 mg, 0.02 mmol), PPh3 (1.0 mg, 0.004 mmol), Et3N
(0.030 g, 0.30 mmol), and HCO2H (0.01 mL, 9 mg,
0.20 mmol) in DMF (2 mL) was heated at 60–70 °C for
30 min, cooled to rt, and treated with water (2 mL). The re-
sulting aqueous solution was extracted with Et2O (3 ×
2 mL), the combined organic layer was dried (Na2SO4) and
concentrated in vacuo, and the residue was subjected to flash
chromatography (hexane) to afford 18 mg (91%) of 5c as
colorless crystals, mp 100 to 101 °C (hexane) (lit. (24a) mp
101 to 102 °C (ethanol); lit. (24b) mp 101 to 102 °C (metha-
1
1354. H NMR (300 MHz, CDCl3) δ: 1.01 (t, J = 7.5 Hz,
3H), 1.20 (t, J = 8.1 Hz, 3H), 1.25–1.30 (m, 15H), 2.63 (q,
J = 7.5 Hz, 2H), 3.14 (q, J = 8.1 Hz, 2H), 3.55 (q, J =
8.1 Hz, 2H), 7.06 (s, 1H), 7.17 (d, J = 7.5 Hz, 1H), 7.72 (d,
J = 7.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ: 12.9, 14.1,
15.6, 25.2, 38.5, 43.3, 83.9, 125.4, 127.7, 135.9, 143.9,
149.9, 171.0. EI-MS m/z (rel. int.): 331 (M+, 21), 273 (100),
232 (16), 188 (6), 158 (7), 105 (8), 55 (4). HR-MS m/z
calcd. for C19H30BNO3: 331.2319; found: 331.2321.
1
nol)). H NMR (25) (500 MHz, CDCl3) δ: 2.60 (s, 6H), 7.50
© 2004 NRC Canada

Cai et al.
203
dried (Na2SO4) and concentrated in vacuo. The residue was
purified by flash column chromatography (hexane) to afford
202 mg (92%) of 15 as colorless crystals, mp 92 to 93 °C
(hexane) (lit. (27) mp 87.5 °C (MeOH)). 1H NMR
(300 MHz, CDCl3) δ: 1.47 (t, J = 7.5 Hz, 3H), 2.84 (s, 3H),
2.96 (q, J = 7.5 Hz, 2H), 7.48–7.65 (m, 3H), 7.78 (s, 1H),
7.81 (d, J = 9.0 Hz, 1H), 8.01 (d, J = 9.0 Hz, 1H), 8.63 (d,
J = 9.0 Hz, 1H), 8.69 (d, J = 9.0 Hz, 1H). 13C NMR
(75 MHz, CDCl3) δ: 16.1, 20.4, 29.2, 121.2, 123.2, 123.4,
126.5, 127.0, 127.2, 127.7, 127.8, 129.2, 130.8, 130.9,
132.3, 135.2, 142.9. EI-MS m/z (rel. int.): 220 (M+, 100),
205 (73), 189 (15), 178 (3), 165 (3), 101 (4). HR-MS m/z
calcd. for C17H16: 220.1252; found: 220.1255.
N,N-Diethyl 3-ethyl-2′,3′-dimethylbiphenyl-2-carboxamide
(12)
According to general procedure B, 1-bromo-2,3-
dimethylbenzene (1.36 mL, 1.85 g, 10.0 mmol) was sub-
jected to reaction with 11 (3.31 g, 10 mmol) in the presence
of Pd(PPh3)4 (0.185 g, 0.16 mmol). Normal workup fol-
lowed by flash chromatography (EtOAc–hexane, 1:5) af-
forded 1.85 g (60%) of 12 as a viscous oil. IR (neat) (cm–1):
1
1634. H NMR (300 MHz, CDCl3) δ: 0.68 (s, 3H), 0.75–
1.04 (br, 3H), 1.28 (t, J = 7.8 Hz, 3H), 2.08 (s, 3H), 2.27 (s,
3H), 2.72 (q, J = 7.8 Hz, 2H), 2.75–3.30 (br, 4H), 3.73 (s,
1H), 6.96–7.25 (m, 6H). 13C NMR (75 MHz, CDCl3) δ:
12.1, 14.1, 15.6, 17.6, 20.9, 28.8, 38.2, 42.8, 125.4, 126.8,
128.0, 129.4, 130.1, 135.1, 137.2, 143.5, 170.8. EI-MS m/z
(rel. int.): 309 (M+, 100), 280 (13), 237 (15), 209 (8), 178
(18), 165 (15), 74 (35). HR-MS m/z calcd. for C21H27NO:
309.2093; found: 309.2086.
N,N-Diethyl 4-tert-butylphenyl carbamate (23)
To a suspension of sodium hydride (0.48 g, 60% in min-
eral oil, 12 mmol) in anhyd THF (20 mL) was added 4-tert-
butylphenol (1.50 g, 10 mmol). After hydrogen evolution
ceased (1 h), diethylcarbamoyl chloride (1.51 mL, 1.62 g,
12 mmol) was added and the reaction mixture was stirred at
rt for 2 h, and treated with water (10 mL). The aqueous layer
was separated and extracted with Et2O (3 × 20 mL). The
combined extract was dried (Na2SO4) and concentrated in
vacuo to give a residue that was purified by flash column
chromatography (EtOAc–hexane, 1:3) to afford 1.49 g
(60%) of 23 as colorless crystals, mp 77 to 78 °C (CH2Cl2)
(lit. (28) mp 86 °C (pentene)). IR (KBr) (cm–1): 1706, 1480,
7-Ethyl-1-methyl-9-phenanthrol (13)
According to general procedure C, treatment of a solution
of 12 (3.09 g, 10 mmol) in THL (20 mL) with a solution of
LDA (25.0 mmol) in THF (80 mL) for 30 min followed by
acidification, normal workup, and flash chromatography
(hexane) afforded 2.24 g (95%) of 13 as colorless crystals,
1
mp 192–195 °C (CH2Cl2). IR (KBr) (cm–1): 3306. H NMR
(300 MHz, CDCl3) δ: 1.28 (t, J = 8.1 Hz, 3H), 2.60 (s, 3H),
2.84 (q, J = 8.1 Hz, 2H), 7.25 (s, 1H), 7.28–7.38 (m, 2H),
7.51 (d, J = 8.4 Hz, 1H), 8.12 (s, 1H), 8.47 (d, J = 8.1 Hz,
1H), 8.63 (d, J = 8.1 Hz, 1H), 10.36 (s, 1H). 13C NMR
(75M Hz, CDCl3) δ: 16.4, 20.5, 29.2, 102.1, 121.5, 123.7,
124.0, 126.1, 126.6, 127.4, 128.2, 128.4, 130.4, 132.2,
132.7, 142.5, 151.8. EI-MS m/z (rel. int.): 236 (M+, 100),
221 (65), 207 (10), 193 (15), 179 (10), 165 (4), 89 (3). HR-
MS m/z calcd. for C17H16O: 236.1201; found: 236.1206.
1
1402, 1277, 1211. H NMR (300 MHz, CDCl3) δ: 1.25 (s,
6H), 1.34 (s, 9H), 3.43 (s, 4H), 7.04–7.10 (m, 2H), 7.36–
7.42 (m, 2H). 13C NMR (75 MHz, CDCl3) δ: 13.8, 14.6,
31.8, 34.7, 42.2, 42.6, 121.4, 126.4, 148.1, 149.6, 154.8. EI-
MS m/z (rel. int.): 249 (M+, 35), 163 (2), 146 (2), 135 (3),
100 (100), 72 (7). HR-MS m/z calcd. for C15H23NO2:
249.1729; found: 249.1736.
7-Ethyl-1-methylphenanthryl-9-trifluoromethanesulfonate
(14)
N,N-Diethyl 4-tert-butyl-2-hydroxybenzamide (24)
A solution of 23 (2.49 g, 10.0 mmol) in anhyd THF
(20 mL) was added dropwise to a solution of s-BuLi
(9.6 mL of 1.25 mol L–1 solution, 12.0 mmol) and TMEDA
(1.07 mL, 1.39 g, 12.0 mmol) in anhyd THF (30 mL) at
–78 °C. The reaction mixture was stirred at –78 °C for 1 h,
allowed to warm to rt over 12 h, and quenched with a satd.
aq. NH4Cl solution (10 mL). The aqueous layer was sepa-
rated and extracted with Et2O (3 × 20 mL), and the com-
bined extract was dried (Na2SO4) and concentrated in vacuo.
The resulting residue was purified by flash column chroma-
tography (EtOAc–hexanes, 1:5) to afford 1.37 g (55%) of 24
as colorless crystals, mp 133 – 135 °C (CH2Cl2). IR (KBr)
According to general procedure D, a solution of 13
(1.18 g, 5.00 mmol) and 2,6-lutidine (0.69 mL, 0.64 g,
6.00 mmol) in CH2Cl2 (100 mL) was treated with triflic an-
hydride (1.01 mL, 1.69 g, 6.00 mmol). Normal workup fol-
lowed by flash chromatography (hexane) afforded 1.20 g
(95%) of 14 as colorless crystals, mp 61 to 62 °C (EtOAc).
1
IR (KBr) (cm–1): 1421, 1208, 1135. H NMR (300 MHz,
CDCl3) δ: 1.41 (t, J = 7.5 Hz, 3H), 2.74 (s, 3H), 2.95 (q, J =
7.5 Hz, 2H), 7.48 (d, J = 7.2 Hz, 1H), 7.57–7.66 (m, 2H),
7.91 (s, 1H), 7.97 (s, 1H), 8.52 (d, J = 9.0 Hz, 1H), 8.64 (d,
J = 9.0 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ: 15.7, 20.1,
29.4, 114.7, 119.3 (q, J = 323 Hz), 120.1, 121.1, 123.7,
129.3, 129.5, 130.2, 130.7, 135.7, 144.3, 144.7. EI-MS m/z
(rel. int.): 368 (M+, 35), 235 (45), 207 (100), 192 (18), 165
(3), 69 (7). HR-MS m/z calcd. for C18H15F3O3S: 368.0684;
found: 368.0689.
1
(cm–1): 3142, 1595, 1268. H NMR (300 MHz, CDCl3) δ:
1.27–1.33 (m, 15H), 3.51 (q, J = 7.2 Hz, 4H), 6.92 (d, J =
17.1 Hz, 1H), 7.27 (d, J = 5.0 Hz, 1H) 7.34 (dd, J = 17.1,
5.0 Hz, 1H), 9.50 (s, 1H). 13CNMR (75 MHz, CDCl3)
δ:13.8, 31.8, 34.4, 42.5, 117.6, 118.1, 124.3, 129.6, 141.4,
156.4, 172.2. EI-MS m/z (rel. int.): 249 (M+, 31), 234 (72),
177 (76), 161 (100), 133 (16), 105 (20), 72 (38). HR-MS
m/z calcd. for C15H23NO2: 249.1729; found: 249.1719.
7-Ethyl-1-methylphenanthrene (15)
A stirred mixture of 14 (0.368 g, 1.00 mmol), Pd(OAc)2
(4.5 mg, 0.02 mmol), PPh3 (10.5 mg, 0.04 mmol), Et3N
(0.42 mL, 0.303 g, 3.00 mmol), and HCO2H (0.08 mL,
92 mg, 2.00 mmol) in DMF (10 mL) was heated at 60–
70 °C for 30 min. The reaction mixture was cooled to rt and
water was added (10 mL). The aqueous layer was separated
and extracted with Et2O (3 × 10 mL), and the extract was
4-tert-Butyl-2-(N,N-diethylcarboxamido)phenyl trifluoro-
methanesulfonate (20)
According to general procedure D, a solution of 24
(2.49 g, 10.0 mmol) and pyridine (0.97 mL, 0.95 g,
12.0 mmol) in CH2Cl2 (100 mL) was treated with triflic an-
© 2004 NRC Canada

204
Can. J. Chem. Vol. 82, 2004
hydride (2.01 mL, 3.38 g, 12.0 mmol). Normal workup fol-
lowed by flash chromatography (EtOAc–hexane, 1:5)
afforded 2.48 g (65%) of 20 as a colorless oil. IR (neat)
119.4 (q, J = 323 Hz), 121.1, 123.6, 125.1, 126.9, 127.7,
128.7, 129.6, 130.1, 130.6, 135.6, 144.9, 151.2. EI-MS m/z
(rel. int.): 396 (M+, 68), 381 (14), 263 (100), 236 (75), 220
(32), 205 (16), 179 (8), 69 (11). HR-MS m/z calcd. for
C20H19F3O3S: 396.1007; found: 396.1008.
1
(cm–1): 1645, 1426, 1215. H NMR (CDCl3) δ: 1.08 (t, J =
7.2 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H), 1.30 (s, 9H), 3.16 (q,
J = 7.2 Hz, 2H), 3.40–3.70 (br, 2H), 7.23 (d, J = 8.6 Hz,
1H), 7.37 (d, J = 2.1 Hz, 1H), 7.40 (dd, J = 8.6, 2.1 Hz, 1H).
13C NMR (CDCl3) δ: 12.7, 14.2, 31.4, 35.1, 39.5, 43.3,
118.8 (q, J = 323 Hz), 121.5, 125.8, 128.0, 130.7, 143.3,
152.1, 166.2. EI-MS m/z (rel. int.): 382 (M+, 71), 309 (100),
233 (38), 161 (73), 72 (69). HR-MS m/z calcd. for
C16H22F3NO4S: 381.1222; found: 381.1234.
7-tert-Butyl-1-methylphenanthrene (27)
A stirred mixture of 26 (0.396 g, 1.00 mmol), Pd(OAc)2
(4.5 mg, 0.02 mmol), PPh3 (10.5 mg, 0.04 mmol), Et3N
(0.42 mL, 0.303 g, 3.00 mmol), and HCO2H (0.08 mL,
92 mg, 2.00 mmol) in DMF (10 mL) was heated at 60–
70 °C for 30 min. The reaction mixture was cooled to rt, wa-
ter (0 mL) was added, and the mixture was extracted with
Et2O (3 × 10 mL). The combined organic extract was dried
(Na2SO4), concentrated to dryness, and the residue was sub-
jected to flash chromatography (hexane) to afford 248 mg
(95%) of 27 as colorless crystals, mp 126 to 127 °C (hex-
ane). 1H NMR (CDCl3) δ: 1.74 (s, 9H), 2.96 (s, 3H), 7.64 (d,
J = 7.4 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 7.93 (dd, J = 8.6,
1.8 Hz, 1H), 7.98 (d, J = 9.3 Hz, 1H), 8.12 (s, 1H), 8.14 (d,
J = 9.2 Hz, 1H), 8.77 (d, J = 8.6 Hz, 1H), 8.82 (d, J =
8.8 Hz, 1H). 13C NMR (CDCl3) δ: 20.5, 32.0, 35.3, 121.7,
123.7, 125.8, 126.9, 127.9, 128.2, 129.4, 131.2, 131.5,
132.6, 135.6, 150.0. EI-MS m/z (rel. int.): 248 (M+, 100),
234 (95), 218 (10), 205 (13), 189 (7), 178 (3). HR-MS m/z
calcd. for C19H20: 248.1565; found: 248.1564.
N,N-Diethyl 3-tert-butyl-2′,3′-trimethyldiphenyl-2-carbox-
amide (19)
According to general procedure B, 2,3-dimethylphenyl-
boronic acid (1.50 g, 10.0 mmol) was subjected to reaction
with 20 (3.82 g, 10 mmol) in the presence of Pd(PPh3)4
(0.185 g, 0.16 mmol). Normal workup followed by flash
chromatography (EtOAc–hexane, 1:5) afforded 2.76 g (82%)
1
of 19 as a viscous oil. IR (cm–1): 1634. H NMR (CDCl3) δ:
0.69 (t, J = 7.2 Hz, 3H), 0.70–1.0 (br, 3H), 1.35 (s, 9H), 2.10
(s, 3H), 2.27 (s, 3H), 2.50–3.90 (br m, 4H), 6.80–7.43 (m,
6H). 13C NMR (CDCl3) δ: 12.2, 13.8, 24.1, 31.6, 34.9, 38.3,
124.4, 125.4, 126.5, 127.6, 128.4, 129.3, 134.7, 137.1,
142.6, 150.3, 151.6, 155.5, 171.1. EI-MS m/z (rel. int.): 337
(M+, 97), 322 (7), 264 (100), 250 (37), 209 (40), 181 (12),
165 (17), 74 (32). HR-MS m/z calcd. for C23H31NO:
337.2406; found: 337.2398.
Acknowledgements
We are grateful to Canadian Network of Toxicology Cen-
ters (CNTC) for support of this research program. XC is a
recipient of a Queen’s Graduate Award (QGA).
7-tert-Butyl-1-methyl-9-phenanthrol (25)
According to general procedure C, treatment of a solution
of 19 (3.37 g, 10 mmol) in THF (20 mL) with a solution of
LDA (25.0 mmol) in THF (80 mL) for 30 min followed by
acidification, normal workup, and flash chromatography
(hexane) afforded 2.38 g (90%) of 25 as a powder that gave
colorless crystals, mp 165–168 °C (CH2Cl2). IR (KBr) (cm–1):
References
1. (a) R. Munoz, B. Guieysse, and B. Mattiasson. Appl.
Microbiol. Biotechnol. 61, 261 (2003); (b) R. van Herwijnen,
P. Wattiau, L. Bastiaens, L. Daal, L. Jonker, D. Springael,
H.A.J. Govers, and J.R. Parsons. Res. Microbiol. 154, 199
(2003).
2. (a) A.C. Wertheimer and A.G. Celewycz. Am. Fish. Soc.
Symp. 18, 518 (1996); (b) W.R. Reeves, R. Barhoumi, R.C.
Burgharat, S.L. Lemke, K. Mayura, T.T. McDonald, T.D.
Philips, and K.C. Donnelly. Environ. Sci. Technol. 35, 1630
(2001); (c) N. Basu, S. Billiard, N. Fragoso, A. Omoike, S.
Tabash, S. Brown, and P. Hodson. Environ. Toxicol. Chem. 20,
1244 (2001).
3. (a) S.M. Billard, K. Wuerbach, and P.V. Hodson. Env. Toxicol.
Chem. 18, 2070 (1999); (b) B.L. Boese, J.O. Lamberson, R.C.
Swartz, R. Ozretich, and F. Cole. Arch. Environ. Contam.
Toxicol. 34, 235 (1998); (c) C.D. Metcalfe, T.L. Metcalfe, Y.
Kiparissis, B.G. Koenig, C. Khan, R.J. Hughes, T.R. Croley,
R.E. March, and T. Potter. Environ. Toxicol. Chem. 20, 297
(2001).
4. (a) Y. Kiparissis, P.V. Hodson, Y. Blazeski, X. Cai, and V.
Snieckus. Proceedings of the Society of Environmental Toxi-
cology and Chemistry, 22nd Annual Meeting, Baltimore,
Maryland, 11–15 Nov. 2001; (b) X. Cai, S. Brown, P. Hodson,
and V. Snieckus. Canadian Network of Toxicology Centres
(CNTC) Annual Symposium Report, Ottawa, Ontario, March
25 and March 26, 2003.
1
3466. H NMR (CDCl3) δ: 1.53 (s, 9H), 2.63 (s, 3H), 5.81
(s, 1H), 7.20 (s, 1H), 7.38–7.45 (m, 2H), 7.81 (dd, J = 8.1,
2.1 Hz, 1H), 8.36 (d, J = 2.1 Hz, 1H), 8.49 (d, J = 8.1 Hz,
1H), 8.64 (d, J = 9.0 Hz, 1H). 13C NMR (CDCl3) δ 20.6,
31.1, 35.7, 103.4, 118.4, 121.3, 123.6, 124.3, 125.5, 126.2,
127.3, 128.2, 130.5, 131.9, 133.4, 149.9, 150.3. EI-MS m/z
(rel. int.): 264 (M+, 100), 250 (50), 232 (13), 221 (22), 194
(13), 179 (12), 165 (9), 11 (8). HR-MS m/z calcd. for
C19H20O: 264.1514 (accurate data could not be obtained due
to oxidation of the sample).
7-tert-Butyl-1-methylphenanthryl-9-trifluoromethane-
sulfonate (26)
According to general procedure D, to a solution of 25
(1.32 g, 5.00 mmol) and 2,6-lutidine (0.69 mL, 0.64 g,
6.00 mmol) in CH2Cl2 (100 mL) was added triflic anhydride
(1.01 mL, 1.69 g, 6.00 mmol). Normal workup followed by
flash chromatography (hexane) afforded 1.72 g (87%) of 26
as colorless crystals, mp 103 to 104 °C (EtOAc). IR (KBr)
1
(cm–1): 1423, 1207, 1139. H NMR (CDCl3) δ: 1.61 (s, 9H),
2.73 (s, 3H), 7.45 (d, J = 7.2 Hz, 1H), 7.56 (t, J = 8.4 Hz,
1H), 7.88 (dd, J = 9.0, 1.8 Hz, 1H), 7.93 (s, 1H), 8.27 (d, J =
1.8 Hz, 1H), 8.44 (d, J = 8.1 Hz, 1H), 8.66 (d, J = 9.0 Hz,
1H). 13C NMR (CDCl3) δ: 20.0, 31.6, 35.5, 114.7, 117.6,
5. W. Krasodomski, M.K. Luczynski, J. Wilamowski, and J.
Sepiol. Tetrahedron, 59, 5677 (2003).
© 2004 NRC Canada

Cai et al.
205
6. (a) P.H. Leake. Chem. Rev. 56, 57 (1956); (b) P.E. Leake. Org.
React. (N.Y.), 9, 409 (1957); (c) P. Hanson, P.W. Lovenich,
S.C. Rowell, P.H. Walton, and A.W. Timms. J. Chem. Soc.
Perkin Trans. 2, 49 (1999); (d) F.W. Wassmundt and W.F.
Kiesman. J. Org. Chem. 60, 196 (1995); (e) R. Duclos, J.S.
Tung, and H. Rapoport. J. Org. Chem. 49, 5243 (1984); (f) B.
Chauncy and E. Gellert. Austr. J. Chem. 22, 993 (1969).
7. A.J. Floyd, S.F. Dyke, and S.E. Ward. Chem. Rev. 76, 509
(1976).
(2000); (b) A.V. Kalinin, M.A. Reed, B.H. Norman, and V.
Snieckus. J. Org. Chem. 68, 5992 (2003).
12. C.B. de Koning, A.L. Rousseau, and W.A.L. van Otterlo. Tet-
rahedron, 59, 7 (2003).
13. R.P. Moody, D. Riedel, L. Ritter, and C.A. Franklin. J.
Toxicol. Environ. Health, 22, 471 (1987).
14. P. Beak and R.A. Brown. J. Org. Chem. 47, 34 (1982).
15. P.J. Stang, M. Hanack, and L.R. Subramanian. Synthesis, 85
(1982).
8. (a) F.B. Mallory and C. Mallory. Org. React. (N.Y.), 30, 1
(1984); (b) F.B. Mallory, M.J. Rudolph, and S.M. Oh. J. Org.
Chem. 54, 4619 (1989); (c) J.C. Estevez, M.C. Villaverde, R.J.
Estevez, J.A. Seijas, and L. Castedo. Can. J. Chem. 68, 964
(1990); (d) M.C. Pampin, J.C. Estévez, R.J. Estévez, M. Mae-
stro, and L. Castedo. Tetrahedron, 59, 7231 (2003); (e) A.
Sugimoto, R. Hiraoka, H. Inoue, T. Adachi. J. Chem. Soc.
Perkin Trans. 1, 1559 (1992); (f) M.K. Lakshman, P.L. Kole,
S. Chaturvedi, J.H. Saugier, H.J.C. Yeh, J.P. Glusker, H.L.
Carrell, A.K. Katz, C.E. Afshar, W. Dashwood, G. Kenniston,
and W.M. Baird. J. Am. Chem. Soc. 122, 12 629 (2000).
9. (a) G. Dyker, J. Korning, and F. Nerenz. Pure Appl. Chem. 68,
323 (1996); (b) G. Dyker P. Siemsen, S. Sostmann, A.
Wiegand, I. Dix, and P.G. Jones. Chem. Ber./Recl. 130, 261
(1997); (c) G. Dyker. Eur. J. Inorg. Chem. 6, 877 (1998);
(d) K.V. Radhakrishnan, E. Yoshikawa, and Y. Yamamoto. Tet-
rahedron Lett. 40, 7533 (1999); (e) E. Yoshikawa and Y.
Yamamoto. Angew. Chem. Int. Ed. 39, 173 (2000); (d) D.
Pena, D. Perez, E. Guitian, and L. Castedo. J. Org. Chem. 65,
6944 (2000); (g) D. Pena, D. Perez, E. Guitian, and L.
Castedo. Synlett, 1061 (2000).
16. R. Pschorr and H. Hofman. Chem. Ber. 39, 3110 (1906).
17. (a) S. Cacchi and G. Ortar. Tetrahedron Lett. 27, 3931 (1986);
(b) R. Crettaz, J. Waser, and Y. Bessard. Org. Process Res.
Dev. 5, 572 (2001); (c) Y. Wan, M. Alterman, M. Larhed, and
A. Hallberg. J. Org. Chem. 67, 6232 (2002); (d) W. Mägerlein,
A.F. Indolese, and M. Beller. Angew. Chem. Int. Ed. 40, 2856
(2001).
18. M.P. Sibi and V. Snieckus. J. Org. Chem. 48, 1935 (1983).
19. S.C. Watson and J.F. Eastham. J. Organomet. Chem. 9, 165
(1967); (b) M. Gau and H.O. House. Org. Synth. Coll. VI, 121
(1988).
20. P. Beak and R.A. Brown. J. Org. Chem. 47, 34 (1982).
21. T. Hasselstrom. J. Am. Chem. Soc. 63, 2627 (1941).
22. W.E. Bachmann and A.L. Wilds. J. Am Chem. Soc. 60, 624
(1938).
23. J.C. Bardham and D. Nasipuri. J. Chem. Soc. 350 (1956).
24. (a) M.S. Newman and K.C. Lilje. J. Org. Chem. 44, 4944
(1979); (b) R.D. Haworth, C.R. Mavin, and G.J. Sheldrick. J.
Chem. Soc. 454 (1934).
25. A. Helms, D. Heiler, and G. McLendon. J. Am. Chem. Soc.
114, 6227 (1992).
10. (a) J.C. Estevez, M.C. Villaverde, R.J. Estevez, and L. Castedo.
Tetrahedron, 49, 2783 (1993); (b) G.A. Kraus and N. Zhang.
Tetrahedron Lett. 43, 9597 (2002); (b) D.C. Harrowven, M.I.T.
Nunn, and D.R. Fenwick. Tetrahedron Lett. 43, 7345 (2002).
11. (a) For other recent application of DoM and DreM methodol-
ogy see: J.-m. Fu and V. Snieckus. Can. J. Chem. 78, 905
26. H.M. Petrassi, T. Klabunde, J. Sacchettini, and J.W. Kelly. J.
Am. Chem. Soc. 122, 2178 (2000).
27. L. Ruzicka and St. Kaufman. Helv. Chim. Acta, 24, 939 (1941).
28. R. Rips, C. Tilloy-Voillaume, J. Peyroux, and P. Rossignol.
Chim. Ther. 5, 418 (1970).
© 2004 NRC Canada