Aryllead triacetates in the synthesis of oxaphenanthrene derivatives

Article abstract of DOI:10.1016/S0040-4039(01)01147-9

Ortho-Halomethylphenyllead triacetates (halo = bromine or chlorine) react with phenols in the presence of triethylamine and a pyridine derivative to afford modest to good yields of dibenzo[b,d]-6H-pyrans.

Full text of DOI:10.1016/S0040-4039(01)01147-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5875–5877
Aryllead triacetates in the synthesis of oxaphenanthrene
derivatives
a,b
a
a,
Alexey Yu. Fedorov, Fabien Carrara and Jean-Pierre Finet *
a
Laboratoire ‘Chimie, Biologie et Radicaux Libres’, UMR 6517, CNRS-Universit e´ s d’Aix-Marseille, 1 et 3,
Facult e´ des Sciences, Saint-J e´ r oˆ me, 13397 Marseille Cedex 20, France
b
Department of Chemistry, Nizhnii-Novgorod Lobachevski State University, 603600 Nizhnii-Novgorod, Russia
Received 16 March 2001; accepted 16 May 2001
Abstract—ortho-Halomethylphenyllead triacetates (halo=bromine or chlorine) react with phenols in the presence of triethylamine
and a pyridine derivative to afford modest to good yields of dibenzo[b,d]-6H-pyrans. © 2001 Elsevier Science Ltd. All rights
reserved.
The dibenzo[b,d]pyran skeleton is present in a number
ortho-halomethylphenyllead triacetate is needed
whereas the range of known aryllead triacetates is
limited to polymethoxy- or polymethyl-phenyl deriva-
tives. In view of the reactions of arylmagnesium
reagents bearing an ortho-chloromethyl group recently
reported by Cahiez and Knochel, we considered the
synthesis of organolead reagents 4 or 7 as possible
1
of natural products, as well as in apomorphine-derived
2
3
s ligands or in progesterone receptor modulators.
Among the various strategies developed for their syn-
4
–8
thesis,
recent ones rely on an intramolecular palla-
7
dium-catalyzed arylation reaction or an intramolecular
11
8
radical cyclization (Path A, Scheme 1). A potentially
attractive alternative would be a one-pot organolead-
mediated ortho-arylation–cyclization sequence (Path B,
Scheme 1).
(
Scheme 2). Indeed, organolead reagents 4 or 7 can
easily be prepared from the corresponding arylboronic
acids 3 or 6. The bromomethyl compound 3 was pre-
pared from ortho-tolylboronic acid by dibenzoyl perox-
ide catalyzed bromination with N-bromosuccinimide in
The selective ortho-arylation of phenols by ligand cou-
pling reaction with aryllead triacetates is now well
12
CCl in 60% yield. The chloro analogue 6 was not
9
4
documented. This reaction is particularly useful for the
obtained when N-chlorosuccinimide was used as the
source of halogen. However, reaction of 2-
chloromethylphenylmagnesium bromide (prepared
from 2-chloromethylphenyl iodide and isopropylmagne-
introduction of electron-rich aryl groups which are
10
frequently observed in natural products. However,
,6-diarylation is generally favoured even if, with a
2
proper choice of conditions, moderate yields of the
mono-arylation products can be obtained. If a second
electrophilic centre is present in the aryllead reagent in
a suitable geometric position, cyclization can be
expected after the first arylation, thus avoiding the
diarylation. But such a sequence requires that the lead
centre is the most reactive one of the two electrophilic
centres. For the synthesis of oxaphenanthrenes, an
11
sium bromide) with boron tris-isopropoxide afforded
the boronic compound 6 in 52% yield. Transmetallation
was performed by reaction of acids 3 or 6 with lead
tetraacetate in the presence of mercuric acetate, accord-
13
ing to Pinhey’s procedure. In this way, the air stable
bromo compound 4 was isolated in 48% yield, and the
air sensitive chloro compound 7 in 78% yield.
Pb(OAc)3
Path B
X
Path A
+
X
O
OH
Scheme 1.
*
0
Corresponding author. Fax: 33 4 91 98 85 12; e-mail: finet@srepir1.univ-mrs.fr
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01147-9

5
876
A. Yu. Fedoro6 et al. / Tetrahedron Letters 42 (2001) 5875–5877
Br
Br
a
b
c
Br
B(OH)2
B(OH)2
Pb(OAc)3
1
2
3
4
Cl
Cl
Cl
d
c
I
B(OH)2
Pb(OAc)3
5
6
7
Scheme 2. (a) BuLi/B(Oi-Pr) ; (b) dibenzoylperoxide/N-bromosuccinimide/CCl ; (c) Pb(OAc) /Hg(OAc) ; (d) i-PrMgBr/
3
4
4
2
B(Oi-Pr)3.
Using the classical procedure for phenol arylation with
aryllead triacetates [phenol 8 or 10, aryllead triacetate 4
cant amount of the product 9. However, when a second
stronger base was added to pyridine, significantly
improved yields were then observed (Table 1, entries 3
and 4). These observations further demonstrated the
importance of pyridine or the related DMAP (4-
dimethylaminopyridine) as a specific ligand in arylation
reactions with aryllead triacetates. As aryllead reagents
generated by boron–lead metal exchange can be advan-
tageously used directly in the arylation reaction, we
generally treated the crude reagent 4 or 7 with the
phenolic substrates.
(
1.1 equiv.), pyridine (3 equiv.) at 45°C in CHCl ], the
3
oxaphenanthrene derivatives 9 or 11 were obtained
directly, although in poor yields (20–25%). Pyridine
plays a determinant, if not completely understood, role
as a ligand in the lead atom sphere during the ligand
coupling process leading to the formation of the ortho-
1
4
arylphenol. In the present system, the arylation step is
followed by an intramolecular cyclization. The bromhy-
dric acid which is liberated can abstract pyridine
molecules from acting as ligand of the aryllead reagent.
This could explain the low yields obtained under these
conditions. However, increasing the amount of pyridine
to 6 equivalents did not improve the yield. A second
possibility is that pyridinium hydrobromide could react
with the postulated (aryloxy)lead intermediate. The
reaction of phenol 8 with the lead reagent 4 in the
presence of a stronger base, TMG (N,N,N%,N%-tetra-
methylguanidine) (3 equiv.), did not afford any signifi-
Moderate to relatively good overall yields were then
obtained with other electron-rich phenols, and a modest
yield was obtained in the reaction with a cyclic b-
ketoester, the 4-hydroxycoumarin derivative 18. It is
interesting to note that even the hindered 3,5-di-tert-
butylphenol 16 afforded the tricyclic compound 17
although in a modest yield (13%) (Table 1).
R1
R1
R2
R3
R2
R3
OH
O
8
9
OH
O
R1
R2
R3
MeO
O
O
MeO
O
O
10
12
14
16
MeO H
MeO
MeO
11
H
H
13
15
17
MeO MeO MeO
t-Bu t-Bu
MeO
OH
MeO
O
H
1
8
19
a
Table 1. Arylation–cyclization with aryllead reagent 4
Entry
Substrate
4
Conditions
Products
Yield %
b
c
c
c
b
c
c
c
c
c
1
2
3
4
5
6
7
8
9
8
8
8
1.1 equiv.
1.1 equiv.
1.4 equiv.
1.4 equiv.
1.1 equiv.
1.4 equiv.
1.4 equiv.
1.4 equiv.
1.4 equiv.
1.4 equiv.
Pyridine (4 equiv.), 45°C, 10 h
Pyridine (4 equiv.), 45°C, 10 h
9
9
9
25
20
55
65
27
60
38
37
13
25
Pyridine (3 equiv.), Et N (3 equiv.), rt, 1 h
3
8
DMAP (3 equiv.), Et N (3 equiv.), rt, 1 h
9
3
10
10
12
14
16
18
Pyridine (5 equiv.), 50°C, 5 h
11
11
13
15
17
19
DMAP (3 equiv.), Et N (3 equiv.), rt, 1 h
3
DMAP (3 equiv.), Et N (3 equiv.), rt, 4 h
3
Pyridine (3 equiv.), Et N (3 equiv.), rt, 10 h
3
Pyridine (3 equiv.), Et N (3 equiv.), rt, 10 h
3
1
0
Pyridine (3 equiv.), Et N (3 equiv.), rt, 5 h
3
a
b
c
3
The reactions were performed in CHCl3 (5 cm /mmol of substrate); DMAP=4-dimethylaminopyridine.
Pure isolated 4 was used.
In situ generated 4 was used.

A. Yu. Fedoro6 et al. / Tetrahedron Letters 42 (2001) 5875–5877
5877
a
Table 2. Arylation–cyclization with aryllead reagent 7
Substrate
8
10
12
14
16
18
Conditions
Products
rt, 10 hb
9
50°C, 10 hb
11
50°C, 6 hb
13
50°C, 10 hc
15
50°C, 10 hc
17
50°C, 6 hc
19
Yield (%)
55
42
33
26
6
21
a
3
The reactions were performed with in situ generated 7 (1.4 equiv.), pyridine or DMAP (3 equiv.), Et N (3 equiv.) in CHCl (5 cm /mmol of
3
3
substrate).
b
c
DMAP (4-dimethylaminopyridine) was used as the coordinating base.
Pyridine was used as the coordinating base.
Phytochemistry 1998, 48, 181–182; 183–184; 185–186; (f)
Zhang, G.-l.; Ruecher, G.; Breitmaier, E.; Mayer, R.;
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3
4
Scheme 3.
When the same system (phenol, aryllead triacetate and
two bases) was applied to the chloromethylphenyllead
reagent 7, slightly lower yields were obtained in all
cases and the reactions were more sluggish, requiring
longer reaction times and/or higher temperatures
5. (a) Wan, P.; Huang, C.-G. J. Chem. Soc., Chem. Com-
mun. 1988, 1193–1195; (b) Shi, Y.; Wan, P. Chem. Com-
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(
50°C) (Table 2).
In conclusion, functional group interconversion of a
dicationic equivalent (A) possessing a more reactive
benzylic centre can be transformed, via a zwitterion (B),
into a second dicationic equivalent (C) in which the
aromatic electrophilic centre is more reactive towards
nucleophilic reagents than the benzylic centre (Scheme
3). Indeed, 2-halomethylphenylboronic acids can be
easily transmetallated with lead tetraacetate to afford
the 2-halomethylphenyllead triacetates 4 or 7, in which
the presence of the halogen atom in the coordinating
sphere of the lead atom does not significantly alter the
usual reactivity of aryllead triacetates towards soft
nucleophiles.
9. (a) Pinhey, J. T. In Comprehensive Organometallic Chem-
istry II; Abel, E. W.; Stone, F. G. A.; Wilkinson, G.,
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461–485; (b) Finet, J.-P. Ligand Coupling Reactions with
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1998; Chapter 7, pp. 205–247.
1
0. Donnelly, D. M. X.; Finet, J.-P.; Guiry, P. J.; Nesbitt, K.
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