Polymer-supported distannanes: A new and efficient synthesis of highly effective reagents for iodine atom transfer cyclisations

Article abstract of DOI:10.1016/j.tetlet.2003.11.039

Polymeric distannanes were synthesised by the cross-linking of polystyrene bound tin hydride functionalities using a palladium mediated dehydrogenative coupling. The polymers were characterised by spectroscopic methods (IR and ¹³C, ¹¹⁹

Full text of DOI:10.1016/j.tetlet.2003.11.039

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 831–834
Polymer-supported distannanes: a new and efficient synthesis of
highly effective reagents for iodine atom transfer cyclisations
*
ꢀ
Alejandro G. Hernan and Jeremy D. Kilburn
Department of Chemistry, School of Chemistry, University of Southampton, Southampton SO17 1BJ, UK
Received 10 October 2003; revised 27 October 2003; accepted 6 November 2003
Abstract—Polymeric distannanes were synthesised by the cross-linking of polystyrene bound tin hydride functionalities using a
palladium mediated dehydrogenative coupling. The polymers were characterised by spectroscopic methods (IR and 13C, 119Sn
NMR) and elemental analysis and were successfully applied to two iodine atom transfer cyclisations, performing as well as solution
based hexaalkylditin reagents and significantly better than previously reported polymer-supported ditin reagents.
Ó 2003 Elsevier Ltd. All rights reserved.
Free radical reactions are an important tool in organic
synthesis and are routinely used in the preparation of
even the most complex target molecules.1 Stannyl radi-
cals have played a central role in the development of this
chemistry, and tributyltin hydride has been one of the
most popular reagents for propagating radical reactions.
Ditin reagents have also been a popular source of
stannyl radicals since homolytic cleavage of tin–tin
bonds takes place under mild conditions.2 Ditin reagents
have been widely used, in particular, for atom transfer
cyclisations3 where premature termination of the radical
chain by a hydrogen atom donor is to be avoided.
However, the toxicity and difficulty of removing
organotin compounds from final products does limit the
use of this methodology. There have been several
approaches to developing alternative reagents for radi-
cal reactions,4 or modified tin reagents, which can be
more easily removed at the end of the reaction.5 Of
these, polymer-supported tin reagents6 offer several
advantages as they can be easily removed by filtration as
well as having the potential to be easily recycled for
further use. There have been several studies on polymer-
supported tin hydride reagents but surprisingly little has
been reported on the preparation and utility of polymer-
supported distannanes. Neumann has described the
preparation of a polymer-supported distannane 1 by
reaction of a dialkyl tin chloride, linked to a macro-
porous polystyrene resin, with a soluble reactive metal
(e.g., lithium naphthalenide).7 However, utilisation of
this resin in atom transfer cyclisations led to significant
amounts of reduced products as well as the desired
cyclised product (vide infra), presumably either as a
consequence of trapping of the radical intermediates by
hydrogen atoms from the polymer backbone,8 or
because of tin hydride impurities in the polymer-sup-
ported distannane reagent.9 We now describe an
experimentally much simpler method for the efficient
preparation of polymer-supported distannanes, on
standard polystyrene resin (1% DVB), which have been
characterised by elemental analysis and gel phase/MAS
NMR (119Sn, 13C and 1H) and which give excellent
results in atom transfer cyclisations, with little, or no,
reduced byproducts.
We have previously described the use of tin chlorides 3
and 4 as polymer-supported reagents for the catalytic
Stille reaction.10 Reduction of dimethyltin chloride resin
4 with LiAlH411 gave the corresponding tin hydride resin
6 (Scheme 1) in quantitative yield as determined by
elemental analysis, gel-phase 13C and 119Sn NMR.12
Addition of catalytic (Pd(PPh3)4) (5 mol %) to resin 6,
pre-swollen in tetrahydrofuran, resulted in immediate
evolution of H2 gas.13 The IR spectrum of the resulting
resin 8 showed the total disappearance of the IR stretch
for Sn–H (ꢀ1800 cmꢁ1). Magic angle spinning (MAS)
119Sn NMR of resin 8 revealed a single peak at a very
similar chemical shift ()99.57 ppm relative to Me4Sn)
compared to that observed for tin hydride resin 6
()98.22 ppm relative to Me4Sn), but the peak for 8 was
Keywords: Distannane; Polymer supported; Atom transfer.
* Corresponding author. Tel.: +44-023-80593596; fax: +44-023-8059-
6805; e-mail: jdk1@soton.ac.uk
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.039

832
A. G. Hernꢀan, J. D. Kilburn / Tetrahedron Letters 45 (2004) 831–834
i)
HO
R
R
R
5 mol%
O
O
Sn R
Sn R
R
NaH, DMF
Cl
O
Sn X
R
Sn R
Sn R
R
Pd(PPh3)4
ii) R2SnCl2, R2SnH2,
AIBN, hν, toluene
3 R = nBu, X = Cl
4 R = Me, X = Cl
2
7 R = nBu
8 R = Me
LiAlH4
1 R = nBu
5 R = nBu, X = H
6 R = Me, X = H
Scheme 1.
much broader than that for 6 presumably as a conse-
quence of the more restricted mobility of the cross-
linked ditin resin compared to the tin hydride resin. A
spectrum (MAS 119Sn NMR) of a 1:1 mixture of 8 and 6
and comparison with the spectra for the separate resins
confirmed the 119Sn peak assignments and indicated that
conversion of the tin hydride to the ditin was essentially
quantitative using this palladium catalysed dehydro-
genation methodology. An identical sequence of reac-
tions was used to convert dibutyltin chloride resin 3 to
ditin resin 7. However, after reduction with LiAlH4,
119Sn NMR analysis of 5 showed two signals at similar
shifts [)80.3 ppm (broad) and )86.2 ppm (sharp)]
revealing a spontaneous partial dehydrogenation14 to
the ditin polymer 7, which was completed by treatment
with catalytic (Pd(PPh3)4) (5 mol %).
ditin resin 8, but was somewhat slower using the steri-
cally more encumbered butyl substituted ditin resin 7.
The more demanding cyclisation of iodoester 11
(Scheme 3) was studied in greater detail. Good yields of
the cyclised product 12 were again obtained using
10 mol % of ditin reagent but the reaction time required
was ꢀ16 h for completion (Table 2, entries 1–6). Again
the sterically more accessible ditin polymer 8 appeared
to perform somewhat better than 7. The cyclisation
could also be carried out using lower amounts of poly-
mer-supported ditin (5 mol % and even 2 mol %) but
yields of the cyclised product were reduced even after
prolonged reaction (Table 2, entries 7–10).
The results are significantly better than those described
previously by Neumann and co-workers,7 who reported,
for example, that cyclisation of the same substrate 11,
using macroporous ditin resin 1, led to mixtures of
reduced starting material 14 and cyclised products 12
and 13 (Table 1, entries 17 and 18). The significantly
better performance of 7 and 8 can probably be attrib-
uted to the greater flexibility and accessibility of the
polystyrene resin used here, and probably to the purity
of the distannane reagent. The results are also on a par
with those achieved using R6Sn2 reagents in solution.
Clearly premature quenching of radical intermediates by
hydrogen atoms abstracted from the solid support is not
an issue in this system.
Both resins 7 and 8 were used in two atom transfer
reactions of iodides 9 and 11. In a typical experiment the
polymer-supported distannane was suspended in a
0.03 M solution of the iodide and the suspension heated
to 80 °C and irradiated using a 100 W UV lamp.
Reactions were monitored by GC and final products
were purified by column chromatography to give iso-
lated yields.
Cyclisation of diallyl amide 9 (Scheme 2) was carried out
with 10 mol % of ditin reagent and very high yields of
cyclised product 10 were obtained with no reduced
byproducts being detected (Table 1). The reaction was
essentially complete in 1 h using the methyl substituted
As anticipated the polymer-supported ditin reagent can
be easily removed from the reaction by filtration and
analysis of isolated products revealed very low residual
tin levels15 (<5–34 ppm) for the various samples tested.
In cases where residual tin was detected (up to 34 ppm)
this is likely to be a consequence of mechanical, rather
than chemical, degradation of the resin on stirring.
O
O
I
7 or 8
N
N
C6H6, hν, reflux
I
9
10
Scheme 2.
O
O
Table 1. Yields from cyclisation of iodide 9 (Scheme 2)
O
X
I
O
Yieldsa (%)
O
O
Entry
Ditin
reagent
Ditin
reagent
(equiv)
Time (h)
7 or 8
+
9
10
C6H6, hν, reflux
1
2
3
7
7
8
0.1
0.1
0.1
1
4
1
24
0
76 (67)
98 (90)
99 (93)
11
12 X = I
13 X = H
14
0
a Yields determined by GC. Isolated yields are in parentheses.
Scheme 3.

A. G. Hernꢀan, J. D. Kilburn / Tetrahedron Letters 45 (2004) 831–834
Table 2. Yields from cyclisation of iodide 11 (Scheme 3)
833
Entry
Ditin reagent
Ditin reagent
(equiv)
Time (h)
Yieldsa (%)
11
70
12
13
14
1
7
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.05
0.05
0.02
0.1
0.1
0.1
0.1
0.1
0.1
0.5
0.1
1
4
30
34
0
0
0
2
7
58
14
60
14
0
5
6
3
7
16
1
80
40
0
4
8
0
0
5
8
4
83 (78)
92 (90)
16
0
0
6
8
16
1
0
8
7
8
75
67
55
65
100
90
61
90
69
9
0
2
8
8
4
22
33
0
2
9
8
16
16
1
0
2
10
11
12
13
14
15
16
17
18
8
30
0
0
5
8b
8b
8b
8c
8c
8c
1d
1d
0
0
4
5
25
0
3
16
1
0
10
2
8
26
0
4
0
3
16
––
––
79
––
0
7
35
5
61
50
36
a Yields determined by GC except for those in parenthesis which are isolated yields.
b Recovered directly from previous reaction.
c Recycled resin (treated with LiAlH4, then Pd(0)) from previous reaction.
d Published results, see Ref. 7.
W. J. Org. Chem. 1995, 60, 2607–2609; Vedejs, E.;
Duncan, S. M.; Haight, A. R. J. Org. Chem. 1993, 58,
3046–3048; fluorous: Curran, D. P.; Hadida, S.; Kim, S.
Y.; Luo, Z. Y. J. Am. Chem. Soc. 1999, 121, 6607–6615.
The polymer-supported distannane can also be recycled
for further use (Table 2, entries 11–16). Resin 8 was
recovered from an initial iodine-transfer cyclisation of
11 (Table 2, entry 6). The resin was dried under vacuum
6. See, for example, (a) Gerigk, U.; Gerlach, M.; Neumann,
W. P.; Vieler, R.; Weintritt, V. Synthesis 1990, 448–452;
(b) Kuhn, H.; Neumann, W. P. Synlett 1994, 123–124; (c)
Dumartin, G.; Kharboutli, J.; Delmond, B.; Pereyre, M.;
Biesemans, M.; Gielen, M.; Willem, R. Organometallics
1996, 15, 19–23; (d) Chemin, A.; Deleuze, H.; Maillard, B.
Eur. Polym. J. 1998, 34, 1395–1404; (e) Nicolaou, K. C.;
Winssinger, N.; Pastor, J.; Murphy, F. Angew. Chem., Int.
Ed. 1998, 37, 2534–2537; (f) Enholm, E. J.; Schulte, J. P.,
II. Org. Lett. 1999, 1, 1275–1277; (g) Enholm, E. J.;
Gallagher, M. E.; Moran, K. M.; Lombardi, J. S.;
Schulte, J. P., II. Org. Lett. 1999, 1, 689–691; (h)
Boussaguet, P.; Delmond, B.; Dumartin, G.; Pereyre, M.
Tetrahedron Lett. 2000, 41, 3377–3380; (i) Zhu, X.;
Blough, B. E.; Carroll, F. I. Tetrahedron Lett. 2000, 41,
9219–9222.
and then reused for the same reaction giving a 25% yield
(GC) of 12 after 16 h (Table 2, entry 13). However, after
reduction with LiAlH4 and subsequent reaction with
Pd(PPh3)4, the same sample of resin then gave a 79%
yield (GC) of 12 after 16 h (Table 2, entry 16).
Acknowledgements
We thank Dr. David Apperley, NMR Service Manager
at the Industrial Research Laboratories, University of
Durham, UK for carrying out the MAS 119Sn NMR
experiments.
7. (a) Junggebauer, J.; Neumann, W. P. Tetrahedron 1997,
53, 1301–1310; (b) Harendza, M.; Junggebauer, J.;
Leßmann, K.; Neumann, W. P.; Tews, H. Synlett 1993,
286–289; (c) Harendza, M.; Leßmann, K.; Neumann, W.
P. Synlett 1993, 283–286.
References and notes
8. Curran, D. P.; Yang, F.; Cheong, J. J. Am. Chem. Soc.
2002, 124, 14993–15000.
9. The absence of an IR absorption for a Sn–H bond
(1805 cmꢁ1) for resin 1 was used to indicate that the level
of tin hydride impurities is low. See Ref. 7a.
1. Radicals in Organic Synthesis; (a) Renaud, P., Sibi, M. P.,
Eds.; Wiley-VCH: Weinheim, Germany, 2001; (b) Par-
sons, A. F. An Introduction to Free Radical Chemistry;
Blackwell Science: Oxford, 2000.
2. Gilbert, B. C.; Parsons, A. F. J. Chem. Soc., Perkin Trans.
2 2002, 367–387.
ꢀ
10. Hernan, A. G.; Guillot, V.; Kuvshinov, A.; Kilburn, J. D.
Tetrahedron Lett. 2003, 44, 8601–8603.
3. Curran, D. P.; Chang, C. T. J. Org. Chem. 1989, 54, 3140–
3157.
11. Weinshenker, N. M.; Crosby, G. A.; Wong, J. Y. J. Org.
Chem. 1975, 40, 1966–1971.
4. For example, tris(trimethylsilyl)silane: Chatgilialoglu, C.
Acc. Chem. Res. 1992, 25, 188–194; hypophosphite salts:
Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. J. Org.
Chem. 1993, 58, 6838–6842; Graham, S. R.; Murphy, J.
A.; Coates, D. Tetrahedron Lett. 1999, 40, 2415–2416.
5. Water soluble: Clive, D. L. J.; Waing, J. J. Org. Chem.
2002, 67, 1192–1198; acid soluble: Clive, D. L. J.; Yang,
12. Polymer 5 (obtained as a mixture of the desired tin hydride
polymer 5 and cross-linked distannane polymer 7): IR
(ATR): mmax ¼ 1803 cmꢁ1 (Sn–H); 119Sn NMR (gel phase in
C6D6; 112 MHz): d ¼ ꢁ80:3 (small, br), )86.2 ppm; Micro-
analysis: Sn: 12.5% (1.06 mmol/g); Cl < 0.1%. Polymer 6:
IR (ATR): mmax ¼ 1822 cmꢁ1 (Sn–H); 13C NMR (gel phase
in C6D6, 75.5 MHz): d 73.1 (br), 45.6 (br), 26.8, 5.3,

834
A. G. Hernꢀan, J. D. Kilburn / Tetrahedron Letters 45 (2004) 831–834
)12.9 ppm; 119Sn MAS NMR (C6D6; 112 MHz):
d
)98.22 ppm; Microanalysis: Sn ¼ 14.8% (1.25 mmol/g);
Cl < 0.1%. Polymer 7: 13C NMR (gel phase in C6D6,
75.5 MHz): d 72 (br), 30 (br), 27 (br), 13, 10 ppm (poorly
resolved spectrum); 119Sn NMR (gel phase in C6D6;
112 MHz): d ¼ ꢁ80:3 (br) ppm; Microanalysis:
Sn ¼ 14.5% (1.23 mmol/g). Polymer 8: 13C NMR (gel
phase in C6D6, 75.5 MHz): d 73 (br), 45.3, 28.1, 7.2,
)7.3 ppm; 119Sn MAS NMR (C6D6; 112 MHz):
d ¼ ꢁ99:57 ppm; Microanalysis: Sn ¼ 14.8% (1.25 mmol/
g).
13. Mitchell, T. N.; Amamria, A.; Killing, H.; Rutschow, D. J.
J. Organomet. Chem. 1986, 304, 257–265.
14. Davies, A. G.; Osie-Kissi, D. K. J. Organomet. Chem.
1994, 474, C8–C10.
15. Tin analysis was carried out by digesting the sample in
acid followed by ICP (inductively coupled plasma) analy-
sis, and was performed by Medac Ltd.