A convenient synthesis of alkyl- and dialkylphenanthren-9-ylamines

Article abstract of DOI:10.1055/s-2001-16090

A variety of alkyl- and dialkylphenanthren-9-ylamines 1 and 2 have been prepared by radical-mediated cyclizations of the corresponding diaryleneamines 3 issued from Homer reactions between appropriate phosphorylated dibenzylamines 4 and halogenoarylaldehydes 5.

Full text of DOI:10.1055/s-2001-16090

1462
PAPER
A Convenient Synthesis of Alkyl- and Dialkylphenanthren-9-ylamines
A
Convenient
Sy
h
nthesis of Al
r
kyl-and
i
Dialkyl
s
phenanthr
t
en-9-y
o
lamines phe Hoarau, Axel Couture,* Eric Deniau, Pierre Grandclaudon
Laboratoire de Chimie Organique Physique, ESA CNRS N° 8009, Université des Sciences et Technologies de Lille, 59655 Villeneuve
d’Ascq Cédex, France
Fax +33(3)20336309; E-mail: Axel.Couture@univ-lille1.fr
Received 5 March 2001; revised 17 April 2001
amination reaction.2 Moreover, this procedure requires
Abstract: A variety of alkyl- and dialkylphenanthren-9-ylamines 1
the tedious and low yielding preparation of biaryl precur-
and 2 have been prepared by radical-mediated cyclizations of the
sors and even though an alternative and shorter route to
corresponding diaryleneamines 3 issued from Horner reactions be-
these parent compounds has been recently developed, all
examples elaborated by this method are invariably alkox-
ylated at the 1-position of the phenanthrene unit.2 At last
the latter methods require harsh conditions and have been
mainly confined to the construction of unsubstituted mod-
el compounds. All these limitations, in conjunction with
the need for photolysis or electrolysis equipment, have
provided increasing incentives to search for alternatives to
these methodologies.
tween appropriate phosphorylated dibenzylamines 4 and halo-
genoarylaldehydes 5.
Key words: aminophenanthrenes, carbanions, Horner reactions,
radical reactions, cyclizations
9-N-Alkyl- and 9-N,N-dialkylaminophenanthrenes repre-
sent a class of aromatic amines which are considered as
valuable building blocks for the synthesis of architectural-
ly sophisticated natural products. In particular, they are in-
volved in the elaboration of a variety of lignans1 but
equally of dioxoaporphines2 and aristolactam3 alkaloids.
The recent and elegant syntheses of the synthetically chal-
lenging natural products steganone,1 cepharadione2 and
piperolactam C3 emphasize the potential of these polycy-
clic aromatic amines. Paradoxically, despite the fact that
these compounds gain interest as target products of syn-
thetic organic methodologies, they still remain accessible
only by a few limited methods. The basic strategies gen-
erally involve the displacement of a variety of nucleofug-
es from the 9-position of a preformed phenanthrene ring
system, namely bromo,4 cyano5 and hydroxy2,6 groups, by
the amine functionality. However, the most convenient
routes are based upon the Curtius rearrangement of
azides7 and the Bischler–Napieralski cyclization of biphe-
nyl acetamide derivatives.2,8 More reliable methods in-
volving the rearrangement of polycondensed triazolyl
derivatives,9 the transformation of spiro-fluorenetriazo-
lines by electrochemical means,10 the photochemically in-
duced or radical-mediated cyclization of 1,2-
diarylaminoethylenes,1,11 the dehydromethoxylation of
aminomethoxydihydrophenanthrenes12 have been also re-
ported. However, all these synthetic routes suffer from
several drawbacks and genuinely lack universality. Thus,
the initially mentioned synthetic methods do not solve the
problems set out by the construction of poly and diversely
substituted model compounds. The Bischler–Napieralski
protocol can only be performed with tertiary amides and
the obtention of 9-N-monoalkylated aminophenanthrenes
necessitates an additional two step procedure involving
conversion into phenanthrols and subsequent Bucherer
In our continuing study aimed at the involvement of
-aminocarbanionic species in the synthesis of alkaloids
and natural products13–16 we wish to report here an alter-
native and versatile synthesis of N-alkyl- and N,N-dialky-
laminophenanthrenes 1 and 2, respectively. Our approach,
which is depicted in the retrosynthetic analysis in
Scheme 1 hinges upon the oxidative radical-mediated cy-
clization of the halogenostilbenic amine intermediates 3
(X or Y = halogen) to generate the phenanthrene ring sys-
tem. Subsequent N-deprotection of the annulated products
2 gives an entry to the N-alkylaminophenanthrenes 1
which could be used for further synthetic planning. Of
central importance was the development of a synthetic
route to the diarylethylene amines 3 securing the E-con-
figuration required for efficient free radical cyclization.
Since Horner reaction on related systems has proved to be
the method of choice for the stereoselective formation of
E-isomers17 we therefore planned to prepare the parent
enamines 3 according to the reaction between the phos-
phorylated benzylamine derivatives 4 (Y = halogen or H)
and suitably substituted arylaldehydes 5 (X = H or halo-
gen).
Since the position of the halogen atom on one or the other
aromatic unit of the two partners involved in the assem-
blage of the diarylaminoethylenes by the Horner protocol
was not a priori critical for the success of our strategy, we
started the synthesis with the preparation of the phospho-
rylated dibenzylamine derivative 4a (Scheme 2, Table 1
and Table 2). This compound was readily obtained by a
Mannich type condensation involving three different
components, i.e. the bromobenzaldehyde derivative 6a,
benzylamine 7 and diphenylphosphane oxide 10.18 Unfor-
tunately, all attempts to metallate this phosphorylated
amine with a variety of bases which allow for the survival
of the bromine atom on the aromatic nucleus, e.g. LDA,
KDA, KHMDS, LTMP, met with no success. We suspect
Synthesis 2001, No. 10, 30 07 2001. Article Identifier:
1437-210X,E;2001,0,10,1462,1470,ftx,en;T01901SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
A Convenient Synthesis of Alkyl- and Dialkylphenanthren-9-ylamines
1463
R2
lamine derivatives 4b–l was then prepared according to
the above-mentioned procedure. It is worth mentioning
that this protocol gives likewise access to the diphe-
nylphosphane oxides 4b–h and the phosphonic acid esters
4i–l (Scheme 2, Table 1 and Table 2). Compounds 4b–h
and 4i–l were smoothly deprotonated with butyllithium or
t-butyllithium, respectively, in THF at –78°C. Subsequent
reaction with the o-halogeno aromatic aldehydes 5a–f fol-
lowed by warming to room temperature to ensure comple-
tion of the reaction and usual work up delivered enamines
3a–l (Scheme 3, Table 3). Such compounds are usually
R2
R3
R3
H
PG
R1
N
N
R4
R5
R1
R4
R5
R6
R6
2
1
R7
R7
R3
R2
R3
R2
R4
+
PG
R1
R4
1. ∆ , 1 h
PG
R1
N
Y
2. (R8)2P(O)H 10-12
10 R8 = Ph
N
Y
X
P
R8
R8
O
R2
OMe
4
X
CHO
11 R8 = OEt
12 R8 = OMe
R3
R4
R5
+
3
R5
N
R1
CHO
R6
R7
H
5
R6
R7
62-85 %
Y
7 R1 = Me
8 R1 = Et
6a-f
PG = Protecting Group
9 R1 = n-Bu
Scheme 1
the deprotonation process to be sensitive to the steric con-
gestion of the model compounds, a phenomenon prece-
dented at structurally similar compounds.19 Accordingly,
we set out to achieve the synthesis of enamines 3a–l
(Y = H, X= halogen) by introducing the halogen substitu-
tion in the “southern” aromatic part of the model com-
pounds through the intermediacy of the halogenated
arylaldehydes 5a–f. An array of phosphorylated dibenzy-
OMe
R2
R3
R4
N
R1
4a-l
P
R8
Y
R8
O
Scheme 2
Table 1 Phosphorylated Dibenzylamine Derivatives 4a–l Prepared
Starting
R1
R2
R3
R4
Y
Phosphorylated Amines 4
Aldehyde
R8
Yield (%)
70
6a
6b
6c
6d
6e
6f
Me
Me
Me
Me
Me
Me
Et
H
OMe
H
OMe
H
Br
H
H
H
H
H
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
Ph
H
Ph
75
H
OMe
OMe
H
Ph
77
OMe
H
Ph
78
-OCH2O-
H
Ph
78
OMe
OMe
OMe
OMe
OMe
OMe
H
Ph
85
6c
6c
6d
6e
6c
6c
H
4g
4h
4i
Ph
82
Bu
Me
Me
Et
H
H
Ph
75
OMe
H
OEt
OEt
OMe
OMe
66
-OCH2O-
H
4j
62
H
H
OMe
OMe
H
4k
4l
71
Bu
H
65
Synthesis 2001, No. 10, 1462–1470 ISSN 0039-7881 © Thieme Stuttgart · New York

1464
C. Hoarau et al.
PAPER
obtained by treatment of the sodium salts derived from ar- They have been used as key intermediates for the prepara-
omatic aminonitriles with halogenobenzyl chlorides20 or tion of natural products or pharmacologically interesting
by reaction of deoxybenzoins with secondary amines.1
compounds.20
Table 2 Spectroscopic and Physical Data of the Phosphorylated Dibenzylamine Derivatives 4a–l
Pro-
duct
Mp
(°C)
1H NMR (CDCl3/TMS)
, J (Hz)
13C NMR (CDCl3/TMS)
, J (Hz)
31P NMR
4a
145–146 2.30 (s, 3 H, NCH3), 3.54 (d, 1 H, J = 13.0, CH2Ar), 39.2 (d, JCP = 6), 55.2, 55.9, 59.7 (d, JCP = 9), 60.3, 32.4
3.71 (s, 3 H, OCH3), 3.82 (s, 6 H, 2 OCH3), 3.97 64.6 (d, JCP = 88), 110.5, 113.3, 123.1 (d, JCP = 10),
(d, 1 H, J = 13.0, CH2Ar), 5.34 (d, 1 H, J = 12.0,
NCHP), 6.65 (d, 2 Harom, J = 8.6), 6.79 (d, 2 Harom
J = 8.6), 6.87 (d, 1 Harom, J = 8.8), 7.22–7.27 (m, 3
124.3 (d, JCP = 6), 128.0 (d, JCP = 11), 128.3 (d,
JCP = 11), 128.4 (d, JCP = 4), 129.6, 130.8 (d,
JCP = 9), 131.3 (d, JCP = 4), 131.4, 131.5 (d, JCP = 4),
131.6 (d, JCP = 8.5), 132.3 (d, JCP = 94), 132.9 (d,
JCP = 99), 146.1, 153.3, 158.4
,
Harom), 7.52–7.60 (m, 5 Harom), 7.99–8.05 (m, 3
Harom
)
4b
4c
4d
149–150 2.48 (s, 3 H, NCH3), 3.27 (d, 1 H, J = 12.1, CH2Ar), 40.0 (d, JCP = 4), 56.2, 59.6 (d, JCP = 11), 65.7 (d,
3.75 (d, 1 H, J = 12.1, CH2Ar), 3.80 (s, 3 H, OCH3), JCP = 87), 113.5, 127.9 (d, JCP = 9.5), 128.0, 128.2
32.2
4.40 (d, 1 H, J = 11.4, NCHP), 6.71 (d, 2 Harom
,
(d, JCP =11), 130.1, 130.8, 130.9 (d, JCP = 10), 131.1
J = 8.6), 6.84 (d, 2 Harom, J = 8.6), 7.11–7.69 (m, 13 (d, JCP = 3), 131.3 (d, JCP = 3), 131.6 (d, JCP = 8.5),
Harom), 7.80–7.95 (m, 2 Harom
)
131.8 (d, JCP = 9), 132.5 (d, JCP = 102), 132.8 (d,
JCP = 96), 144.6, 158.5
162–163 2.45 (s, 3 H, NCH3), 3.26 (d, 1 H, J = 14.1, CH2Ar), 39.9 (d, JCP = 4), 55.1, 55.2, 59.5 (d, JCP = 11), 64.9 32.3
3.69 (s, 3 H, OCH3), 3.73 (s, 3 H, OCH3), 3.75 (d, 1 (d, JCP = 88), 113.4, 113.5, 122.8 (d, JCP = 3), 128.1
H, J = 14.1, CH2Ar), 4.39 (d, 1 H, J = 11.9, NCHP), (d, JCP = 11), 128.2 (d, JCP = 11), 130.0, 130.1 (d,
6.69 (d, 2 Harom, J = 8.6), 6.80 (d, 2 Harom, J = 8.6),
6.81 (d, 2 Harom, J = 8.6), 7.10–7.26 (m, 3 Harom),
JCP = 8), 130.9, 131.1 (d, JCP = 3), 131.3 (d, JCP = 3),
131.7 (d, JCP = 9), 131.9 (d, JCP = 8), 132.7 (d,
JCP = 94), 133.0 (d, JCP = 99), 158.6, 159.2
7.46–7.52 (m, 7 Harom) 7.83–7.89 (m, 2 Harom
)
201–202 2.35 (s, 3 H, NCH3), 3.25 (d, 1 H, J = 13.2, CH2Ar), 40.0 (d, JCP = 4), 55.2, 55.6, 55.9, 59.5 (d, JCP = 11), 32.2
3.75 (d, 1 H, J = 13.2, CH2Ar), 3.77 (s, 3 H, OCH3), 65.2 (d, JCP = 88), 110.4, 113.4, 114.6 (d, JCP = 7),
3.84 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 4.30 (d, 1 124.3 (d, JCP = 9), 124.3 (d, JCP = 4), 128.0 (d,
H, J = 11.5, NCHP), 6.69 (d, 2 Harom, J = 11.2), 6.77 JCP = 11), 128.2 (d, JCP = 10), 130.0, 130.9, 131.0 (d,
(d, 1 Harom, J = 8.4), 6.81 (d, 2 Harom, J = 11.2), 6.95 JCP = 8), 131.1 (d, JCP = 3), 131.3 (d, JCP = 3), 131.7
(dd, 1 Harom, J = 8.4, 1.9), 7.20–7.30 (m, 4 Harom),
7.38–7.62 (m, 5 Harom), 7.80–7.86 (m, 2 Harom
(d, JCP = 8.5), 132.2 (d, JCP = 99), 132.7 (d, JCP = 94),
148.3, 148.6, 158.6
)
4e
4f
129–130 2.35 (s, 3 H, NCH3), 3.25 (d, 1 H, J = 13.2, CH2Ar), 39.9 (d, JCP = 4.5), 55.2, 59.5 (d, JCP = 11), 65.2 (d, 32.2
3.65 (d, 1 H, J = 13.2, CH2Ar), 3.70 (s, 3 H, OCH3), JCP = 89), 100.0, 107.8, 111.7 (d, JCP = 7), 113.5,
4.30 (d, 1 H, J = 12.0, NCHP), 5.92 (s, 2 H,
OCH2O), 6.70 (d, 2 Harom, J = 9.6), 6.71 (d, 1 Harom
J = 9.1), 6.80 (d, 2 Harom, J = 9.6), 6.92 (dd, 1 Harom
124.4 (d, JCP = 4), 125.3 (d, JCP = 8.5), 128.1 (d,
JCP = 10), 128.2 (d, JCP = 10), 130.0, 130.8, 131.1 (d,
JCP = 8), 131.15 (d, JCP = 2.5), 131.3 (d, JCP = 2.5),
,
,
J = 9.1, 2.0), 7.20–7.60 (m, 9 Harom), 7.75–7.85 (m, 131.7 (d, JCP = 9), 132.5 (d, JCP = 102), 132.9 (d,
2 H) JCP = 100), 147.2, 147.4, 158.5
132–133 2.45 (s, 3 H, NCH3), 3.29 (d, 1 H, J = 13.2, CH2Ar), 40.0 (d, JCP = 4), 55.1, 56.2, 59.6 (d, JCP = 11), 60.8, 32.3
3.70 (s, 3 H, OCH3), 3.72 (d, 1 H, J = 13.2, CH2Ar), 65.8 (d, JCP = 87), 108.9 (d, JCP = 8), 113.5, 126.7 (d,
3.74 (s, 6 H, 2 OCH3), 3.77 (s, 3 H, OCH3), 4.29 JCP = 3), 128.0 (d, JCP = 11), 128.2 (d, JCP = 11),
(d, 1 H, J = 11.3, NCHP), 6.66 (d, 2 Harom, J = 8.6), 130.0, 130.7, 130.9 (d, JCP = 8), 131.1 (d, JCP = 3),
6.72 (s, 2 Harom), 6.79 (d, 2 Harom, J = 8.6), 7.14–7.22 131.4 (d, JCP = 3), 131.7 (d, JCP = 8.5), 132.6 (d,
(m, 3 Harom), 7.42–7.51 (m, 5 Harom), 7.79–7.85 (m, JCP = 95), 152.6, 158.6
2 Harom
)
4g
131–132 0.95 (t, 3 H, J = 7.0, CH3), 2.20–2.26 (m, 1 H,
NCH2), 3.06 (d, 1 H, J = 13.5, CH2Ar), 3.36–3.43
13.7, 45.4 (d, JCP = 5), 55.1, 55.2, 54.8 (d, JCP = 9), 32.5
113.4, 123.7 (d, JCP = 3), 128.0 (d, JCP = 11), 128.1
(m, 1 H, NCH2), 3.75 (s, 3 H, OCH3), 3.78 (s, 3 H, (d, JCP = 11), 130.1, 130.9, (d, JCP = 8), 131.2, 131.5,
OCH3), 4.11 (d, 1 H, J = 13.5, CH2Ar), 4.39 (d, 1 H, 132.0 (d, JCP = 8), 132.4 (d, JCP = 99), 132.8 (d,
J = 12.8, NCHP), 6.70 (d, 2 Harom, J = 8.5), 6.80–
JCP = 7), 132.8 (d, JCP = 95), 158.4, 159.1
6.85 (m, 4 Harom), 7.27–7.29 (m, 3 Harom), 7.40–7.55
(m, 7 Harom), 7.76–7.83 (m, 2 Harom
)
Synthesis 2001, No. 10, 1462–1470 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Convenient Synthesis of Alkyl- and Dialkylphenanthren-9-ylamines
1465
Table 2 Spectroscopic and Physical Data of the Phosphorylated Dibenzylamine Derivatives 4a–l (continued)
Pro-
duct
Mp
(°C)
1H NMR (CDCl3/TMS)
, J (Hz)
13C NMR (CDCl3/TMS)
, J (Hz)
31P NMR
4h
114–115 0.90 (t, 3 H, J = 6.4, CH3), 1.20–1.22 (m, 2 H, CH2), 14.2, 20.2, 30.5, 51.1, 51.2, 55.1, 55.2, 59.5, 62.1 (d, 32.2
1.23–1.40 (m, 2 H, CH2), 2.19–2.22 (m, 1 H, JCP = 88), 113.4, 123.6, 128.0 (d, JCP = 11), 128.1 (d,
NCH2), 3.05 (d, 1 H, J = 13.4, CH2Ar), 3.27 (m, 1 H, JCP = 11), 128.2 (d, JCP = 11), 130.0, (d, JCP = 9),
NCH2), 3.75 (s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 130.2, 131.0 (d, JCP = 3), 131.3 (d, JCP = 3), 131.2 (d,
4.13 (d, 1 H, J = 13.4, CH2Ar), 4.40 (d, 1 H, J = 12.4, JCP = 3), 131.5, 132.0 (d, JCP = 8.5), 132.4 (d,
NCHP), 6.72 (d, 2 Harom, J = 8.8), 6.81 (d, 2 Harom
J = 8.8), 6.78–6.84 (m, 2 Harom), 7.14–7.30 (m, 3
Harom), 7.35–7.58 (m, 7 Harom), 7.71–7.83 (m, 2
,
JCP = 114), 132.9 (d, JCP = 7), 133.0 (d, JCP = 101),
158.4, 159.1
Harom
)
4i
oil
oil
oil
oil
1.03 (t, 3 H, J = 7.1, CH3), 1.37 (t, 3 H, J = 7.1, CH3), 16.2 (d, JCP = 6), 16.5 (d, JCP = 6), 39.7 (d, JCP = 4.5), 23.6
2.40 (s, 3 H, CH3N), 3.29 (d, 1 H, J = 13.0, CH2Ar), 55.1, 55.7, 55.8, 59.1 (d, JCP = 13), 62.2 (d, JCP = 7),
3.65 (d, 1 H, J = 13.0, CH2Ar), 3.77 (s, 3 H, CH3O), 62.5 (d, JCP = 7), 63.7 (d, JCP = 163), 110.5, 113.6,
3.86 (s, 6 H, 2 CH3O), 3.88–3.97 (m, 3 H, CH2OP 113.8 (d, JCP = 8), 123.4 (d, JCP = 10), 124.3 (d,
+ CHP), 4.13–4.27 (m, 2 H, CH2OP), 6.83 (d, 2
Harom, J = 8.8), 6.84 (d, 1 Harom, J = 8.3), 6.97 (dd, 1
Harom, J = 8.3, 1.3), 7.04 (d, 1 Harom, J = 1.3), 7.22 (d,
2 Harom, J = 8.8)
JCP = 4), 130.0, 130.9, 148.4, 148.7, 158.7
4j
4k
4l
1.03 (t, 3 H, J = 7.1, CH3), 1.32 (t, 3 H, J = 7.1, CH3), 16.2 (d, JCP = 6), 16.6 (d, JCP = 6), 39.6 (d, JCP = 5), 23.5
2.34 (s, 3 H, CH3N), 3.26 (d, 1 H, J = 13.1, CH2Ar), 55.2, 59.1 (d, JCP = 13), 62.2 (d, JCP = 7), 62.6 (d,
3.69–3.73 (m, 2 H, CH2Ar + CHP), 3.74 (s, 3 H,
JCP = 7), 65.9 (d, JCP = 163), 101.1, 107.8, 110.9 (d,
CH3O), 3.87–3.95 (m, 2 H, CH2OP), 4.15–4.22 (m, JCP = 8), 113.6, 124.5 (d, JCP = 10), 124.5 (d,
2 H, CH2OP), 5.91 (s, 2 H, OCH2O), 6.75 (d, 1
Harom, J = 8.7), 6.81 (d, 2 Harom, J = 8.6), 6.84 (dd, 1
Harom, J = 8.7, 1.4), 7.00 (d, 1 Harom, J = 1.4), 7.21 (d,
2 Harom, J = 8.6)
JCP = 4.5), 130.0, 130.9, 147.3, 147.4, 158.7
1.08 (t, 3 H, J = 7.0, CH3), 2.21–2.28 (m, 1 H,
NCH2), 3.09 (d, 1 H, J = 13.5, CH2Ar), 3.10–3.16
(m, 1 H, NCH2), 3.44 (d, 3 H, J = 10.5, POCH3),
13.4, 44.7 (d, JCP = 7), 52.4 (d, JCP = 7), 53.9 (d,
JCP = 7), 54.3 (d, JCP = 10), 55.1, 55.2, 59.7 (d,
JCP = 164), 113.5, 113.6, 124.1 (d, JCP = 6), 130.0,
26.4
3.75 (s, 3 H, CH3O), 3.77 (s, 3 H, CH3O), 3.86 (d, 3 131.6, 131.9 (d, JCP = 9), 158.6, 159.3
H, J = 10.5, POCH3), 4.05 (d, 1 H, J = 13.5, CH2Ar),
4.12 (d, 1 H, J = 25.8, CHP), 6.84 (d, 2 Harom
,
J = 8.5), 6.88 (d, 2 Harom, J = 8.5), 7.26 (d, 2 Harom
J = 8.5), 7.38 (d, 2 Harom, J = 8.5)
,
0.80 (t, 3 H, J = 7.1, CH3), 1.21–1.35 (m, 4 H, 2
CH2), 2.18–2.22 (m, 1 H, NCH2), 3.00–3.04 (m, 1
14.0, 20.2, 30.3, 50.3 (d, JCP = 7), 52.4 (d, JCP = 7), 26.5
53.6 (d, JCP = 7), 54.6 (d, JCP = 10), 55.1, 55.15, 59.7
H, NCH2), 3.07 (d, 1 H, J = 13.4, CH2Ar), 3.41 (d, 3 (d, JCP = 164), 113.5, 113.6, 124.1 (d, JCP = 6),
H, J = 10.4, POCH3), 3.74 (s, 3 H, CH3O), 3.76 (s, 3 130.0, 131.6, 132.0 (d, JCP = 9), 158.6, 159.3
H, CH3O), 3.82 (d, 3 H, J = 10.5, POCH3), 4.05 (d,
1 H, J = 13.4, CH2Ar), 4.09 (d, 1 H, J = 26.0, CHP),
6.82 (d, 2 Harom, J = 8.5), 6.86 (d, 2 Harom, J = 8.5),
7.24 (d, 2 Harom, J = 8.5), 7.36 (d, 2 Harom, J = 8.5)
a Satisfactory microanalyses obtained: C 0.29, H 0.27, N 0.31.
Once again the Horner reaction seems to be sensitive to and 6.0 ppm, respectively) using the substituent shielding
the steric congestion of the parent phosphorylated diben- constants.21 It is worth noting that the exclusively formed
zylamines since its application to the bulkier diphe- isomers were uniformly of the E-structure, regardless of
nylphosphane oxides 4g,h failed to give the expected the degree of substitution of these model compounds, the
enamines 3i,j even though 4g,h could be successfully nature of the halogen substituent and of the temporarily
deprotonated with BuLi (D incorporation after D2O activating phosphorylated agent. Since a marked tendency
quenching). However, enamines 3i,j were gratifyingly ob- of enamines to undergo hydrolysis under standard isola-
tained starting from less hindered dimethoxyphosphoryl tion treatments was observed they were directly submitted
derivatives 4k,l by making use of t-BuLi as the base to the well documented oxidative radical cyclization con-
(Scheme 3, Table 3).
ditions.22 The radical reaction was performed by slow
dropwise addition of a benzene solution of tributyltin hy-
dride and AIBN to a refluxing benzene solution of 3a–l
under argon. This protocol delivered the fused dialkylami-
nophenanthrenes 2a–j with satisfactory yields (Scheme3,
The configuration of the double bond was established by
NOE experiments and above all by comparison of the
chemical shift of the olefinic protons of 3a–l (5.55 0.05
ppm) with that calculated for the E- and Z-isomers (5.6
Synthesis 2001, No. 10, 1462–1470 ISSN 0039-7881 © Thieme Stuttgart · New York

1466
C. Hoarau et al.
PAPER
1. n-BuLi , THF , -78 °C for 4b-f
t-BuLi , THF , -78 °C for 4i-l
5
a
b
c
d
e
f
R5
H
H
H
H
H
R6
H
R7
H
X
Br
I
R5
X
H
H
2.
R2
OMe OMe Br
R6
CHO
5a-f
R3
OMe
OMe
OMe
H
Br
Br
R2
R7
3. -78 °C to rt
R4
R5
O-CH2-O
R3
R4
N
R1
OMe OMe OMe Br
X
N
R1
4b-f
4i-l
3a-l
P
R8
R8
O
R6
R7
OMe
R2
R2
R3
R3
n-Bu3SnH , AIBN
Benzene , ∆
H
N
N
Pd/C , HCOONH4 , MeOH
86-94 %
R4
R5
R1
R4
R5
R1
42-61 %
over two steps
R6
R6
2a-j
1a-j
R7
R7
Scheme 3
Table 3 and Table 4). Interestingly, the radical-mediated the single isomers 2f,g. The final removal of the p-meth-
cyclization process turned out highly regioselective since oxybenzyl protection of the amino group proved more
cyclocondensations of compounds 3f,g, which are liable problematic than we had anticipated. This may probably
to furnish mixtures of regioisomers, afforded exclusively be due to the fact that the 9,10 carbon–carbon bond of the
Table 3 Enamines 3a–l, Dialkylphenanthren-9-ylamines 2a–j and Alkylphenanthren-9-ylamines 1a–j Prepared
R1
R2
R3
R4
R5
R6
R7
X
Starting
Materials
Enamine 3 Amine 2
Amine 1
Yield (%)
Yield (%)a
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
I
4b + 5a
4b + 5b
4b + 5c
4c + 5a
4c + 5b
4c + 5d
4c + 5e
4d + 5a
4i + 5a
4e + 5a
4j + 5a
4f + 5d
4k + 5f
4l + 5f
3a
3k
3b
3c
3l
2a
2a
2b
2c
2c
2d
2e
2f
44
47
48
42
45
51
61
55
57
52
55
56
57
48
1a
92
H
H
H
H
OMe
H
OMe
H
Br
Br
I
1b
1c
91
86
OMe
OMe
OMe
OMe
H
H
OMe
H
Br
Br
Br
Br
Br
Br
Br
Br
Br
3d
3e
3f
1d
1e
1f
89
90
88
-OCH2O-
OMe OMe
OMe OMe
-OCH2O-
H
H
H
H
3f
2f
H
H
3g
3g
3h
3i
2g
2g
2h
2i
1g
92
-OCH2O-
H
H
OMe OMe OMe
OMe
H
1h
1i
94
89
91
H
H
OMe
OMe
H
H
OMe OMe
OMe OMe
OMe
OMe
Bu
3j
2j
1j
a Yields calculated over two steps starting from 4.
Synthesis 2001, No. 10, 1462–1470 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Convenient Synthesis of Alkyl- and Dialkylphenanthren-9-ylamines
1467
Table 4 Spectroscopic and Physical Data of the Dialkylphenanthren-9-ylamines 2a–j Prepared
Producta
Mp
1H NMR (CDCl3/TMS)
13C NMR (CDCl3/TMS)
(°C)
, J (Hz)
, J (Hz)
2a
122–123
135–136
81–82
2.81 (s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 4.25 (s, 2 H, CH2Ar),
6.90 (d, 2 Harom, J = 8.7), 7.28 (s, 1 Harom), 7.35 (d, 2 Harom, J = 8.7), 123.1, 124.5, 125.1, 126.4, 126.5, 126.7,
7.51–7.58 (m, 2 Harom), 7.62–7.70 (m, 2 Harom), 7.78 (dd, 1 Harom
41.4, 55.3, 60.4, 113.8, 115.1, 122.4,
,
127.7, 127.9, 129.5, 130.7, 131.7, 132.5,
158.8
J = 9.3, 3.2), 8.47 (dd, 1 Harom, J = 7.1, 3.2), 8.62 (dd, 1 Harom
J = 6.1, 3.5), 8.72 (dd, 1 Harom, J = 7.5, 3.2)
,
2b
2c
2d
2e
2f
2.79 (s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 4.03 (s, 3 H, OCH3),
41.5, 55.3, 55.9, 56.0, 60.6, 103.4, 107.8,
4.10 (s, 3H, OCH3), 4.24 (s, 2 H, CH2Ar), 6.90 (d, 2 Harom, J = 7.8), 113.7, 114.7, 122.1, 122.6, 124.5, 125.3,
7.16 (s, 1 Harom), 7.24 (s, 1 Harom), 7.35 (d, 2 Harom, J = 7.8), 7.56– 126.2, 127.5, 128.5, 130.0, 130.7, 131.1,
7.63 (m, 2 Harom), 7.96 (s, 1 Harom), 8.47 (d, 1 Harom, J = 7.9), 8.55 146.9, 148.3, 149.5, 158.7
(d, 1 Harom, J = 7.9)
2.80 (s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 4.02 (s, 3 H, OCH3),
4.25 (s, 2 H, CH2Ar), 6.98 (d, 2 Harom, J = 8.5), 7.16 (s, 1 Harom),
7.28–7.34 (m, 3 Harom), 7.49–7.55 (m, 2 Harom), 7.75 (dd, 1 Harom
J = 9.3, 4.2), 8.07 (d, 1 Harom, J = 2.4), 8.38 (d, 1 Harom, J = 9.0),
8.53 (dd, 1 Harom, J = 9.3, 4.2)
41.4, 55.3, 55.5, 60.5, 104.6, 113.0,
113.8, 116.1, 122.5, 123.5, 124.7, 126.2,
126.8, 127.8, 129.0, 129.5, 130.0, 133.1,
158.4, 158.8
,
76–77
2.75 (s, 3 H, NCH3), 3.80 (s, 3 H, OCH3), 3.99 (s, 3 H, OCH3),
41.5, 55.5, 55.6, 60.6, 104.4, 104.9,
112.9, 113.7, 115.9, 116.5, 119.1, 124.2,
4.01 (s, 3 H, OCH3), 4.19 (s, 2 H, CH2Ar), 6.88 (d, 2 Harom
,
J = 8.5), 7.12 (s, 1 Harom), 7.19 (dd, 1 Harom, J = 8.7, 2.4), 7.33 (d, 2 126.2, 127.7, 129.2, 129.5, 130.8, 132.5,
Harom, J = 8.5), 7.67 (d, 1 Harom, J = 8.7), 7.90 (d, 1 Harom, J = 2.4), 146.4, 157.2, 158.1, 158.7
7.97 (d, 1 Harom, J = 2.5), 8.39 (d, 1 Harom, J = 9.6)
191–192
135–136
158–159
107–108
2.75 (s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 4.00 (s, 3 H, OCH3),
4.20 (s, 2 H, CH2Ar), 6.06 (s, 2 H, OCH2O), 6.88 (d, 2 Harom
J = 8.6), 7.06 (s, 1 Harom), 7.10 (s, 1 Harom), 7.21 (dd, 1 Harom
41.6, 55.3, 55.4, 60.7, 100.9, 101.2,
103.9, 105.2, 113.2, 113.7, 115.6, 123.0,
123.1, 126.2, 127.4, 130.7, 146.7, 147.2,
147.7, 158.2, 158.8
,
,
J = 9.2, 2.6), 7.33 (d, 2 Harom, J = 8.6), 7.80 (d, 1 Harom, J = 2.6),
7.87 (s, 1 Harom), 8.34 (d, 1 Harom, J = 9.2)
2.85 (s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 3.91 (s, 3 H, OCH3),
40.9, 55.3, 55.8, 55.9, 60.6, 103.7, 104.8,
113.3, 113.8, 121.9, 124.2, 124.7, 125.8,
4.12 (s, 3 H, OCH3), 4.23 (s, 2 H, CH2Ar), 6.90 (d, 2 Harom
,
J = 8.5), 7.25 (s, 1 Harom), 7.38 (d, 2 Harom, J = 8.5), 7.46–7.53 (m, 126.2, 127.3, 127.8, 129.1, 130.8, 132.0,
2 Harom), 7.77 (dd, 2 Harom, J = 7.5, 2.7), 7.81 (s, 1 Harom), 8.02 (s, 147.7, 149.1, 158.1
1 Harom), 8.46 (dd, 1 Harom, J = 7.5, 2.4)
2g
2h
2.75 (s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 4.21 (s, 2 H, CH2Ar),
6.11 (s, 2 H, OCH2O), 6.88 (d, 2 Harom, J = 8.3), 7.27 (s, 1 Harom), 114.5, 122.1, 124.9, 125.9, 126.0, 127.8,
7.34 (d, 2 Harom, J = 8.3), 7.45–7.56 (m, 2 Harom), 7.75 (dd, 1 Harom
J = 9.3, 4.1), 7.88 (s, 1 Harom), 8.05 (s, 1 Harom), 8.41 (dd, 1 Harom
41.7, 55.2, 60.3, 100.3, 102.4, 113.7,
,
,
127.9, 129.6, 130.6, 131.9, 147.7, 147.9,
158.7
J = 9.0, 2.4)
2.81 (s, 3 H, NCH3), 3.82 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3),
3.95 (s, 3 H, OCH3), 4.01 (s, 3 H, OCH3), 4.05 (s, 3 H, OCH3),
41.2, 55.3, 55.4, 55.8, 60.5, 60.7, 61.3,
101.3, 107.9, 113.8, 115.8, 116.0, 119.9,
127.8, 128.2, 128.7, 129.05, 129.1,
4.07 (s, 3 H, OCH3), 4.17 (s, 2 H, CH2Ar), 6.91 (d, 2 Harom
,
J = 8.3), 7.19 (dd, 1 Harom, J = 7.7, 1.4), 7.28 (s, 1 Harom), 7.39 (d, 2 130.9, 142.5, 145.5, 152.4, 152.7, 157.5,
Harom, J = 8.3), 7.69 (d, 1 Harom, J = 7.7), 7.85 (s, 1 Harom), 9.07 (d, 158.7
1 Harom, J = 1.4)
2i
2j
91–92
1.02 (t, 3 H, J = 6.9, CH3), 3.13 (q, 3 H, J = 6.9, NCH2), 3.75 (s, 3 11.4, 46.5, 55.2, 55.3, 55.8, 56.8, 60.4,
H, OCH3), 3.97 (s, 3 H, OCH3), 3.98 (s, 6 H, 2 OCH3), 4.01 (s, 61.3, 104.4, 108.0, 115.3, 115.4, 115.9,
3 H, OCH3), 4.24 (s, 2 H, CH2Ar), 6.81 (d, 2 Harom, J = 8.5), 6.95 121.4, 124.3, 125.6, 129.5, 131.0, 132.7,
(s, 1 Harom), 7.01 (s, 1 Harom), 7.20 (dd, 1 Harom, J = 9.1, 2.6), 7.29 145.6, 152.2, 152.5, 158.2, 158.5
(d, 2 Harom, J = 8.5), 8.41 (d, 1 Harom, J = 9.1), 9.08 (d, 1 Harom
J = 2.8)
,
oil
0.88 (t, 3 H, J = 7.4, CH3), 1.34 (m, 2 H, CH2), 1.57 (m, 2 H, CH2), 14.1, 20.6, 23.3, 28.7, 51.9, 55.1, 55.3,
3.16 (t, 2 H, J = 7.4, NCH2), 3.77 (s, 3 H, OCH3), 4.02 (s, 3 H,
55.8, 58.0, 60.5, 61.3, 104.5, 108.2,
OCH3), 4.05 (s, 3 H, OCH3), 4.08 (s, 3 H, OCH3), 4.12 (s, 3 H,
113.6, 115.4, 115.6, 116.0, 124.5, 125.6,
OCH3), 4.31 (s, 2 H, CH2Ar), 6.87 (d, 2 Harom, J = 8.6), 7.05 (s, 1 129.6, 130.9, 131.1, 132.9, 141.4, 145.9,
Harom), 7.15 (s, 1 Harom), 7.30–7.35 (m, 3 Harom), 8.56 (d, 1 Harom
,
152.4, 152.6, 158.4, 158.6
J = 9.1), 9.22 (d, 1 Harom, J = 2.6)
a Satisfactory microanalyses obtained: C 0.25, H 0.23, N 0.32.
Synthesis 2001, No. 10, 1462–1470 ISSN 0039-7881 © Thieme Stuttgart · New York

1468
C. Hoarau et al.
PAPER
phenanthrene ring system of 2a–j holds simultaneously desired N-alkylaminophenanthrenes 1a–j (Table 3 and
the disadvantages linked to its marked degree of double Table 5).
bond character which may account for its sensitivity with
regard to hydrogenolysis conditions and also to its still de-
termining enamine character. After some experimentation
we found that the benzylic protection of the amino group
In summary, the goal of our program, to develop a general
and versatile approach to the synthesis of N-alkyl and
N,N-dialkylaminophenanthrenes, has been met with full
success. This synthetic route, which complements the ex-
could be easily removed with Pd on C and ammonium for-
istent methodologies, offers special advantages including
mate in methanol thus providing excellent yields of the
high efficiency, procedural simplicity, mildness of reac-
Table 5 Spectroscopic and Physical Data of the Alkylphenanthren-9-ylamines 1a–j Prepared
Producta
Mp
1H NMR (CDCl3/TMS)
13C NMR (CDCl3/TMS)
(°C)
, J (Hz)
, J (Hz)
c
1a
1b
88–89b
–
138–139
94–95
3.07 (s, 3 H, NCH3), 4.02 (br s, 4 H, OCH3 + NH), 4.07 (s, 3 31.8, 55.8, 56.1, 101.7, 103.8, 107.0, 119.2,
H, OCH3), 6.73 (s, 1 Harom), 7.12 (s, 1 Harom), 7.53 (dt, 1 Harom
,
120.4, 123.0, 124.5, 125.2, 126.2, 128.8,
130.5, 141.3, 146.7, 149.7
J = 8.1, 1.2), 7.62 (dt, 1 Harom, J = 8.2, 1.2), 7.86 (dd, 1 Harom
J = 8.1, 1.2), 8.00 (s, 1 Harom), 8.53 (dd, 1 Harom, J = 7.9, 1.2)
,
1c
3.06 (s, 3 H, NCH3), 4.00 (s, 3 H, OCH3), 4.30 (br s, 1 H, NH), 31.0, 55.4, 99.9, 105.0, 115.8, 120.0, 121.8,
6.66 (s, 1 Harom), 7.21 (dd, 1 Harom, J = 9.0, 2.4), 7.38 (t, 1 Harom
J = 7.6), 7.49 (t, 1 Harom, J = 7.2), 7.70 (dd, 1 Harom, J = 8.0,
2.4), 7.76 (d, 1 Harom, J = 9.0), 8.07 (d, 1 Harom, J = 2.4), 8.45
(dd, 1 Harom, J = 8.0, 2.1)
,
122.4, 124.8, 126.7, 127.0, 132.6, 134.4,
142.4, 158.3
1d
140–141
3.06 (s, 3 H, NCH3), 3.97 (s, 3 H, OCH3), 4.01 (br s, 4 H,
31.2, 55.5, 55.6, 100.2, 104.8, 105.4, 115.6,
OCH3 + NH), 6.65 (s, 1 Harom), 7.16 (dd, 1 Harom, J = 8.7, 2.5), 116.6, 120.5, 122.0, 125.8, 128.0, 128.9,
7.22 (dd, 1 Harom, J = 9.1, 2.5), 7.63 (d, 1 Harom, J = 8.7), 7.81 140.7, 158.0
(d, 1 Harom, J = 9.1), 7.85 (d, 1 Harom, J = 2.5), 7.97 (d, 1 Harom
,
J = 2.5)
1e
1f
178–179
119–120
3.11 (s, 3 H, NCH3), 3.99 (br s, 4 H, OCH3 + NH), 6.03 (s, 2 31.1, 55.4, 100.6, 100.9, 104.3, 104.4, 108.5,
H, OCH2O), 6.58 (s, 1 Harom), 7.07 (s, 1 Harom), 7.15 (dd, 1
Harom, J = 9.0, 2.6), 7.77 (d, 1 Harom, J = 8.0), 7.80 (s, 2 Harom
114.6, 118.3, 120.3, 122.4, 129.5, 132.3,
141.3, 146.1, 148.3, 150.2
)
3.07 (s, 3 H, NCH3), 4.01 (s, 3 H, OCH3), 4.09 (s, 3 H, OCH3), 31.2, 55.9, 101.1, 101.15, 104.1, 120.2,
4.22 (br s, 1 H, NH), 6.74 (s, 1 Harom), 7.14 (s, 1 Harom), 7.37 121.9, 122.6, 124.9, 125.6, 125.9, 126.8,
(dd, 1 Harom, J = 7.7, 1.0), 7.42 (dd, 1 Harom, J = 7.7, 1.0), 7.71 133.1, 141.9, 149.0
(dd, 1 Harom, J = 7.7, 1.0), 7.98 (s, 1 Harom), 8.37 (dd, 1 Harom
,
J = 7.7, 1.0)
1g
1h
1i
155–156
115–116
135–136
102–103
3.07 (s, 3 H, NCH3), 4.10 ( br s, 1 H, NH), 6.10 (s, 2 H,
OCH2O), 6.74 (s, 1 Harom), 7.24 (s, 1 Harom), 7.34 (t, 1 Harom
J = 7.9), 7.43 (d, 1 Harom, J = 7.8), 7.70 (d, 1 Harom, J = 7.8), 8.03 142.2, 147.8
(s, 1 Harom), 8.31 (d, 1 Harom, J = 7.9)
31.2, 98.6, 101.3, 101.4, 101.7, 121.4, 122.1,
122.7, 125.2, 126.1, 126.7, 127.3, 133.1,
,
3.05 (s, 3 H, NCH3), 3.97 (br s, 4 H, OCH3 + NH), 4.01 (s, 3 31.5, 55.4, 55.9, 60.5, 61.3, 97.7, 103.8,
H, OCH3), 4.03 (s, 3 H, OCH3), 4.04 (s, 3 H, OCH3), 6.79 (s, 108.1, 116.1, 119.5, 124.2, 125.9, 127.7,
1 Harom), 7.10 (s, 1 Harom), 7.14 (d, 1 Harom, J = 8.5), 7.63 (d, 1 127.8, 139.9, 142.5, 152.4, 153.0, 156.0
Harom, J = 8.5), 9.00 (s, 1 Harom
)
1.40 (t, 3 H, J = 7.1, CH3), 3.33 (q, 2 H, J = 7.1, NCH2), 3.96 14.7, 38.7, 55.2, 55.7, 60.3, 61.3, 100.6,
(br s, 7 H, 2 OCH3 + NH), 3.97 (s, 6 H, 2 OCH3), 6.55 (s, 103.3, 108.5, 112.8, 115.0, 119.3, 121.1,
1 Harom), 6.89 (s, 1 Harom), 7.15 (dd, 1 Harom, J = 9.0, 2.7), 7.77 121.4, 132.2, 132.5, 139.5, 141.3, 152.4,
(d, 1 Harom, J = 9.0), 9.11 (d, 1 Harom, J = 2.7)
152.7, 158.1
1j
1.02 (t, 3 H, J = 7.3, CH3), 1.55 (m, 2 H, CH2), 1.78 (m, 2 H, 14.0, 20.6, 31.6, 43.0, 55.3, 55.7, 60.4, 61.4,
CH2), 3.30 (t, 2 H, J = 7.0, NCH2) 4.00 (br s, 10 H, 3 OCH3 100.5, 103.3, 108.6, 112.8, 115.0, 119.4,
+ NH), 4.01 (s, 3 H, OCH3), 6.58 (s, 1 Harom), 6.92 (s, 1 Harom), 121.0, 132.3, 132.6, 139.5, 141.4, 152.4,
7.17 (dd, 1 Harom, J = 9.0, 2.1), 7.78 (d, 1 Harom, J = 9.0), 9.15 152.8, 158.1
(d, 1 Harom, J = 2.1)
a Satisfactory microanalyses obtained: C 0.27, H 0.29, N 0.23.
b Lit.6 mp 88.5–89.5.
c See Ref.32
Synthesis 2001, No. 10, 1462–1470 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Convenient Synthesis of Alkyl- and Dialkylphenanthren-9-ylamines
1469
Dialkyl-phenanthren-9-ylamines 2a–j; General Procedure
To a solution of crude 3a–l in dry degassed toluene (250 mL), re-
fluxing under Ar, was added a solution of Bu3SnH (875 mg, 3
mmol) and AIBN (330 mg, 2 mmol) in anhyd degassed toluene (20
mL) dropwise over 30 min. Once the addition was finished, reflux-
ing was kept up for a further 30 min. Benzene was evaporated under
reduced pressure and the crude solid residue dissolved in MeCN
(100 mL). This solution was washed with hexane (5 50 mL) and
concentrated in vacuo to yield a solid residue, which was purified
by flash column chromatography on silica gel using EtOAc–petro-
leum ether (1:1) as eluent. Solid compounds 2a–i were finally re-
crystallized from hexane–toluene.
tion conditions and easy accessibility to the reaction part-
ners. The versatility of this process should be rewarded by
giving easy access to a wide array of natural and biologi-
cally active compounds. Further exploitation along these
lines is under way in our laboratory.
Melting point determinations were carried out on a Reichert-Ther-
1
mopan apparatus and were recorded uncorrected. H, 13C and 31P
NMR spectra were measured at 300 MHz, 75 MHz and 121 MHz,
respectively, on a Bruker AM 300 spectrometer as solutions in
CDCl3 with TMS as internal standard or H3PO4 as external stan-
dard. Elemental analyses were determined at the CNRS microanal-
ysis centre. Compounds were purified until observed as single spots
on TLC (Merck Kieselgel 60 F254). For flash chromatography, Mer-
ck silica gel 60 (230–400 mesh ASTM) was used. All solvents were
dried and distilled according to standard procedures. Dry glassware
for moisture-sensitive reactions was obtained by oven-drying and
assembly under Ar. An inert atmosphere was obtained with a stream
of Ar and glassware equipped with rubber septa; reagent transfer
was performed by syringe. Petroleum ether refers to the fraction
boiling at 40–60 °C.
Alkylphenanthrene-9-ylamines 1a–j; General Procedure
A solution of compounds 2a–j (3 mmol) in MeOH (25 mL) was
stirred with activated Pd/C (10%, 5 mg) and HCO2NH4 (183 mg, 3
mmol). The mixture was refluxed for 30 min, filtered through
Celite® and the solvent removed under reduced pressure. The crude
residue was dissolved in CH2Cl2 (20 mL) and washed with water (2
10 mL). After drying of the organic phase (MgSO4), concentration
in vacuo left a solid, which was purified by chromatography on ba-
sic alumina (Merck aluminum oxide 90 active basic, 70–230 mesh
ASTM) using a mixture EtOAc–petroleum ether (30:70) as eluent.
Final recrystallization from pentane–toluene delivered the target
aminophenanthrenes 1a–j.
The commercially available aromatic aldehydes 6b–f and haloge-
nated arylaldehydes 5a,b were recrystallized or distilled under re-
duced pressure before use. The diversely substituted
bromobenzaldehydes 5c,23 5d,24 5e,25 5f26 and 6a27 and N-Alkyl-4-
methoxybenzylamines 7,28 829 and 930 were prepared according to
already reported procedures. Diphenylphosphane oxide 10 was ob-
tained by a known procedure.31,32
Acknowledgement
This research was supported by the Centre National de la Recherche
Scientifique and MENESR (grant to C. H.).
Phosphorylated Dibenzylamines 4a–l; General Procedure
A solution of N-alkylbenzylamine 7–9 (20 mmol) in toluene (10
mL) was slowly added to a cooled (0°C) solution of the appropriate
(halogeno)arylaldehyde 6a–f (20 mmol) in toluene (20 mL) under
Ar. The mixture was warmed to room temperature and then refluxed
over a period of 1 h. Ph2P(O)H (10; 4.1 g, 20 mmol for compounds
4a–h), (EtO)2P(O)H (11; 4.7 g, 20 mmol for compounds 4i,j) or
(MeO)2P(O)H (12; 2.7 g, 20 mmol for compounds 4k,l) was then
added, the mixture refluxed for an additional hour and the water
formed removed by azeotropic distillation using a Dean–Stark ap-
paratus. The solvent was removed and the crude product containing
the diphenylphosphane oxide 4a–h triturated with Et2O, filtered and
purified by flash column chromatography using a mixture of ace-
tone–petroleum ether (60:40) as eluent. Compounds 4a–h were fi-
nally purified by recrystallization from hexane–toluene. The crude
product containing the oily diethoxyphosphorylated amines 4i,j or
dimethoxyphosphorylated amines 4k,l was purified by flash col-
umn chromatography using a mixture of acetone–hexanes (60:40)
as eluent and the compounds 4i,j and 4k,l thus obtained were used
directly in the next step.
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