been mainly devoted to tin hydride mediated radical
SCHEME 1. Synthesis of the Polymer-supported
Triorganotin Iodide 3aa
1
6
reactions, but examples involving Stille cross-coupling
1
7
13f,14a,18
reactions or allylation reactions
reported.
have also been
In our case, we chose the polymer-supported tri-
organotin iodide 3a, which has been previously described
and characterized.19 The tetramethylene spacer aims at
ensuring sufficient mobility and accessibility to the
13d,16d,19
functionality as pointed out previously.
Further-
more, the problem of tin releasing, which usually occurs
when tin is located on the â-position relative to the
aromatic ring of the polystyrene support, is avoided.1
Accordingly and because of its ease of formation and good
loading (1.1-1.3 mmol.g ), resin 3a appeared to be
among the more suitable ones for our solid-phase ap-
plication.
3d,16d
a
Reagents and conditions: (a) n-BuLi/TMEDA, cyclohexane,
6
5 °C. (b) Br-(CH2)4-Cl, THF, 0 °C to rt. (c) Bu2SnPhLi, THF, rt.
(d) I , EtOH, 60 °C.
-
1
2
spectrum, which showed total disappearance of the well-
defined absorption band at 726 cm indicative of the Sn-
Ph bond. Solid-state
-1
Polymer-supported triorganotin halides were prepared
1
3d,16d,19
119
according to the litterature
1
1
in three steps (Scheme
Sn MAS NMR of the polymer-
). Treatment of the lithiated Amberlite XE 3052
-bromo-4-chlorobutane gave resin 1, which was stan-
SnPhLi to afford stannylated polymer
. Halodearylation of 2 with a solution of iodine in
0,21
with
supported triorganotin iodide 3a revealed a single signal
at 104 ppm (reference Ph Sn, δSn ) -97.35 ppm). A
4
comparison with the 1 Sn MAS NMR spectra of the
stannylated polymer 2 (δ ) -20 ppm) was indicative of
its complete conversion into trialkyltin iodide 3a in the
limits of the NMR measurement.22
19
nylated with Bu
2
2
ethanol led to the corresponding supported triorganotin
iodide 3a.
We then studied the efficiency of the polymer-sup-
ported triorganotin halide 3a on the selective bromin-
ation of aromatic amines for comparison with the liquid-
phase synthesis using soluble trimethyltin chloride. A
variety of aromatic amines were selected and sub-
mitted to the bromination reaction after conversion to
N-triorganostannylamines (Table 1). In a typical proce-
dure, a solution of the N-lithio aromatic amine 5 (ArNH-
Li), formed by treating the corresponding amine 4 with
n-BuLi in diethyl ether, was added at -78 °C under argon
to a stirred mixture of solid-supported triorganotin
reagent 3a in diethyl ether. The temperature of -78 °C
was chosen in order to avoid side reactions when other
reactive groups are contained in the molecule, as for
instance with 4i. The resulting intermediate 6 was react-
ed in situ with bromine (without further characterization
The loading of the solid support was evaluated to be
.30 mmol.g from halogen and tin elemental analyses.
The formation of the polymer-supported triorganotin
halide 3a was first established on the basis of the IR
-
1
1
(
13) (a) Weinshenker, N. M.; Crosby, G. A.; Wong, J. Y. J. Org.
Chem. 1975, 40, 1966-1971. (b) Gerick, U.; Gerlach, M.; Neumann,
W. P.; Vieler, R.; Weintritt, V. Synthesis 1990, 448-452. (c) Neumann,
W. P.; Peterseim, M. React. Polym. 1993, 20, 189-205. (d) Ruel, G.;
The, N. K.; Dumartin, G.; Delmond, B.; Pereyre, M. J. Organomet.
Chem. 1993, 444, C18-C20. (e) Chemin, A.; Deleuze, H.; Maillard, B.
Eur. Polym. J. 1998, 34, 1395-1404. (f) Delmond, B.; Dumartin, G. In
Solid State Organometallic Chemistry: Methods and Applications;
Gielen, M., Willem, R., Wrackmeyer, B., Eds.; John Wiley & Sons:
Chichester, U.K., 1999; pp 445-471. (g) Gastaldi, S.; Stien, D.
Tetrahedron Lett. 2002, 43, 4309-4311.
(14) (a) Enholm, E. J.; Gallagher, M. E.; Moran, K. M.; Lombardi,
J. S.; Schulte, J. P., II. Org. Lett. 1999, 1, 689-691. (b) Enholm, E. J.;
Schulte, J. P., II. Org. Lett. 1999, 1, 1275-1277. (c) Zhu, X.; Blough,
B. E.; Caroll, F. I. Tetrahedron Lett. 2000, 41, 9219-9222.
23
of the supported N-stannylated amine ) and the reaction
(
15) Dumartin, G.; Kharboutli, J.; Delmond, B.; Frangin, Y.; Pereyre,
M. Eur. J. Org. Chem. 1999, 781-783.
mixture was stirred for 2 h before filtration (Scheme 2).
After the usual treatments and concentration of the
filtrate, the crude bromoanilines were submitted to
analyses in order to establish the selectivity of the
reaction, both for regioselectivity and for ratio monosub-
stitution products/polysubstitution products (Table 1).
When compared to the liquid-phase synthesis using
(
16) (a) Gerlach, M.; J o¨ rdens, F.; Kuhn, H.; Neumann, W. P.;
Peterseim, M. J. Org. Chem. 1991, 56, 5971-5972. (b) Bokelmann,
C.; Neumann, W. P.; Peterseim, M. J. Chem. Soc., Perkin Trans. 1
1
8
992, 3165-3166. (c) Neumann, W. P.; Peterseim, M. Synlett 1992,
01-802. (d) Dumartin, G.; Ruel, G.; Kharboutli, J.; Delmond, B.;
Connil, M.-F.; Jousseaume, B.; Pereyre, M. Synlett 1994, 952-954.
(
17) (a) Kuhn, H.; Neumann, W. P. Synlett 1994, 123-124.
(
b) Nicolaou, K. C.; Winssinger, N.; Pastor, J.; Murphy, F. Angew.
Chem., Int. Ed. 1998, 37, 2534-2537. (c) Hern a´ n, A. G.; Guillot, V.;
Kuvshinov, A.; Kilburn, J. D. Tetrahedron Lett. 2003, 44, 8601-8603.
Bu
b), the use of polymer-supported N-stannylated reagents
3 3
SnCl (Table 1, entry 1a) or Me SnCl (Table 1, entry
1
(18) (a) Cossy, J.; Rasamison, C.; Gomez Pardo, D.; Marshall, J. A.
Synlett 2001, 629-633. (b) Cossy, J.; Rasamison, C.; Gomez Pardo, D.
J. Org. Chem. 2001, 66, 7195-7198. (c) Stien, D.; Gastaldi, S. J. Org.
Chem. 2004, 69, 4464-4470.
6a-i (obtained in situ from triorganotin halide 3a and
aromatic amines 4a-i through their N-lithioderivatives
5
a-i) allows an improved selectivity with a higher
(19) (a) Ruel, G.; Dumartin, G.; Delmond, B.; Lal e` re, B.; Donard,
O. F. X.; Pereyre, M. Appl. Organomet. Chem. 1995, 9, 591-595.
b) Dumartin, G.; Kharboutli, J.; Delmond, B.; Pereyre, M.; Biesemans,
M.; Gielen, M.; Willem, R. Organometallics 1996, 15, 19-23.
c) Dumartin, G.; Pourcel, M.; Delmond, B.; Donard, O.; Pereyre, M.
preference for the monosubstitution, which occurs mainly
(
on the para position relative to the amino group to afford
(
Tetrahedron Lett. 1998, 39, 4663-4666. (d) Mercier, F. A. G.; Biese-
mans, M.; Altmann, R.; Willem, R.; Pintelon, R.; Schoukens, J.;
Delmond, B.; Dumartin, G. Organometallics 2001, 20, 958-962.
(22) It is noteworthy that these 119Sn chemical shifts are in good
agreement with those reported in solution for organotin reagents with
similar functionalities. See: (a) Smith, P. J.; Tupciauskas, A. P. Annu.
Rep. NMR Spectrosc. 1978, 8, 291-370. (b) Wrackmeyer, B. Annu. Rep.
NMR Spectrosc. 1985, 16, 73-186. (c) Wrackmeyer, B. Annu. Rep.
NMR Spectrosc. 1999, 38, 203-264.
(23) In liquid phase, organolithium amides are known to be trapped
by triorganotin halides to afford the corresponding N-stannylated
amines. Because of the high sensitivity of this type of reagent to
moisture, MAS NMR characterization of 6a-i was not attempted.
(20) Macroporous resin available from Rohm & Haas as 700 µm
beads with permanent pores of 90 nm (manufacturer specifications).
These values have been reexamined by the Bordeaux group and
measured as 550-600 µm for the beads diameter and 200 nm as an
2
1
average pores size.
(
21) Pourcel, M. Ph.D. Dissertation, University of Bordeaux I, 1997;
pp 57-66.
J. Org. Chem, Vol. 70, No. 7, 2005 2871