Removal, recovery, and recycling of triarylphosphonium-supported tin reagents for various organic transformations

Article abstract of DOI:10.1021/ol701447q

Phosphonium-supported tin reagents and catalysts were prepared and were shown to be effective in Stille couplings, radical dehalogenations, radical cyclizations, and carbonyl allylations. Not only could the tin residues be removed from the crude reaction mixture through a phase separation process but also they could be recovered and recycled.

Full text of DOI:10.1021/ol701447q

ORGANIC
LETTERS
2007
Vol. 9, No. 18
3591-3594
Removal, Recovery, and Recycling of
Triarylphosphonium-Supported Tin
Reagents for Various Organic
Transformations
Jean-Christophe Poupon, David Marcoux, Jean-Manuel Cloarec, and
Andre´ B. Charette*
De´partement de Chimie, UniVersite´ de Montre´al, P.O. Box 6128, Station Downtown,
Montre´al (Que´bec), Canada H3C 3J7
andre.charette@umontreal.ca
Received June 19, 2007
ABSTRACT
Phosphonium-supported tin reagents and catalysts were prepared and were shown to be effective in Stille couplings, radical dehalogenations,
radical cyclizations, and carbonyl allylations. Not only could the tin residues be removed from the crude reaction mixture through a phase
separation process but also they could be recovered and recycled.
Triorganotin derivatives are extremely versatile and useful
reagents in organic synthesis and radical chemistry.1 Nev-
ertheless, these compounds are toxic2 and sometimes mal-
odorous, and tin byproducts are usually difficult to remove
from the desired reaction products.3 Furthermore, contamina-
tion from stannane residues is a major concern in the
synthesis of pharmaceuticals and radiopharmaceuticals.
Alternatives to tin reagents have been disclosed, but no
reagent is as broadly applicable as the parent tin hydride
reagents.4 Recently, we have described the use of the
tetraarylphosphonium unit as a solubility control group for
triphenylphosphine and DEAD.5,6 Because the molecular
weight of the tributyltin subunit constitutes a little bit less
than half of the total molecular weight of the phosphonium-
supported tin reagent, it was not clear whether the solubility
properties of the reagent would still be primarily dictated
by the phosphonium group. The phosphonium reagents are
typically very soluble in chlorinated solvents, and they can
(1) (a) Neumann, W. P. Synthesis 1987, 665. (b) Curran, D. P. Synthesis
1988, 417. (c) Curran, D. P. Synthesis 1988, 489. (d) Radicals in Organic
Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001.
(e) Organotin Chemistry, 2nd ed.; Davies, A. L., Ed.; Wiley-VCH:
Weinheim, New York, 2004.
(2) Thoonen, S. H. L.; Deelman, B. J.; van Koten, G. J. Organomet.
Chem. 2004, 689, 2145.
(4) For a discussion of this issue, see: (a) Baguley, P. A.; Walton, J. C.
Angew. Chem., Int. Ed. 1998, 37, 3073. (b) Studer, A.; Amrein, S. Synthesis
2002, 835.
(5) (a) Poupon, J. C.; Boezio, A. A.; Charette, A. B. Angew. Chem., Int.
Ed. 2006, 45, 1415. (b) Zoute, L.; Lacombe, C.; Quirion, J. C.; Charette,
A. B.; Jubault, P. Tetrahedron Lett. 2006, 47, 7931.
(6) For reviews on soluble supports: (a) Chen, J. N.; Yang, G. C.; Zhang,
H. Q.; Chen, Z. X. React. Funct. Polym. 2006, 66, 1434. (b) Dickerson, T.
J.; Reed, N. N.; Janda, K. D. Chem. ReV. 2002, 102, 3325. Bergbreiter, D.
E. Chem. ReV. 2002, 102, 3345.
(3) Several approaches have been reported to remove tin hydride residues
from reaction mixtures: (a) Berge, J. M.; Roberts, S. M. Synthesis 1979,
471. (b) Leibner, J. E.; Jacobus, J. J. Org. Chem. 1979, 44, 449. (c) Curran,
D. P.; Chang, C. T. J. Org. Chem. 1989, 54, 3140. (d) Farina, V. J. Org.
Chem. 1991, 56, 4985. (e) Crich, D.; Sun, S. X. J. Org. Chem. 1996, 61,
7200. (f) Renaud, P.; Lacote, E.; Quaranta, L. Tetrahedron Lett. 1998, 39,
2123. (g) Edelson, B. S.; Stoltz, B. M.; Corey, E. J. Tetrahedron Lett. 1999,
40, 6729. (h) Salomon, C. J.; Danelon, G. O.; Mascaretti, O. A. J. Org.
Chem. 2000, 65, 9220.
10.1021/ol701447q CCC: $37.00
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Published on Web 08/02/2007

be precipitated out of solution by ether, hexane, or toluene
addition. In this communication, we report that phosphonium
salts can be used as effective solubility control groups for
tin reagents involved in Stille coupling reactions, in carbonyl
allylation reactions, and in radical-mediated processes such
as the dehalogenation and cyclization reactions.7-10 We also
demonstrate that the tin byproducts can be removed by a
simple phase separation upon ether or hexane addition and
recycled if needed.
The Stille reaction12 involving vinyltin reagent 3 using Fu’s
catalyst13 was initially tested. Treatment of various aryl
bromides with catalytic Pd(P(t-Bu3P))2 in 1,4-dioxane led
to corresponding Stille coupling products in high yields
(Table 1). The reactivity of this reagent was comparable to
Table 1. Stille Coupling with Phosphonium-Supported Vinyltin 3
We first chose to test the more conveniently prepared
triphenylalkylphosphonium-supported tin chloride salt 2
obtained in three steps from triphenylphosphine (allylation
with allyl bromide, anion exchange, and hydrostannylation)
(Scheme 1). Conversion of 2 into the vinyltin reagent 3 was
Scheme 1. Preparation of Phosphonium-Supported Tin
Chloride
a
Isolated yields. The yield in parentheses was obtained with tributylvi-
nyltin. b rt for 16 h. c 45 °C for 20 h. d Pd(P(t-Bu)3) (7.5 mol %) and 3 (3.5
equiv) were used.
achieved upon treatment with vinylmagnesium bromide.
Alternatively, NaBH3CN reduction of 2 in the presence of
BHT led to the tin hydride reagent 4. Although the solubility
properties of the reagents bearing this scaffold are not as
suitable as those of the parent substituted tetraarylphospho-
nium salts,11 their ease of synthesis led us to further
investigate them as reagents and catalysts for tin-mediated
processes.
that of tributylvinylstannane under these conditions. The
removal of the tin byproducts was achieved by evaporation
of the reaction mixture, dissolution in dichloromethane
followed by hexane addition, and filtration. Concentration
of the filtrate under reduced pressure afforded the desired
tin-free coupling product.14,15 It should also be pointed out
that the resulting tin bromide could be recovered and recycled
into the vinyltin reagent upon treatment with vinylmagnesium
bromide (90% overall yield).
(7) For pioneering work on removal of tin reagents, see: (a) Light, J.;
Breslow, R. Tetrahedron Lett. 1990, 31, 2957. (b) Clive, D. L. J.; Yang,
W. J. Org. Chem. 1995, 60, 2607.
(8) For solid supported tin reagents: (a) Neumann, W. P.; Peterseim,
M. React. Polym. 1993, 20, 189. (b) Gerigk, U.; Gerlach, M.; Neumann,
W. P.; Vieler, R.; Weintritt, V. Synthesis 1990, 448. (c) Kuhn, H.; Neumann,
W. P. Synlett 1994, 123. (d) Gerlach, M.; Jordens, F.; Kuhn, H.; Neumann,
W. P.; Peterseim, M. J. Org. Chem. 1991, 56, 5971. (e) Neumann, W. P.;
Peterseim, M. Synlett 1992, 801. (f) Nicolaou, K. C.; Winssinger, N.; Pastor,
J.; Murphy, F. Angew. Chem., Int. Ed. 1998, 37, 2534. (g) Hernan, A. G.;
Kilburn, J. D. Tetrahedron Lett. 2004, 45, 831. (h) Hernan, A. G.; Guillot,
V.; Kuvshinov, A.; Kilburn, J. D. Tetrahedron Lett. 2003, 44, 8601. (i)
Chre´tien, J. M.; Zammattio, F.; Le Grognec, E.; Paris, M.; Cahingt, B.;
Montavon, G.; Quintard, J. P. J. Org. Chem. 2005, 70, 2870. (j) Chre´tien,
J. M.; Zammattio, F.; Gauthier, D.; Le Grognec, E.; Paris, M.; Quintard, J.
P. Chem.-Eur. J. 2006, 12, 6816. (k) Chre´tien, J. M.; Mallinger, A.;
Zammattio, F.; Le Grognec, E.; Paris, M.; Montavon, G.; Quintard, J. P.
Tetrahedron Lett. 2007, 48, 1781. (l) Chemin, A.; Deleuze, H.; Maillard,
B. J. Chem. Soc., Perkin Trans. 1999, 1, 137.
The next reaction that was investigated was the tin hydride
catalyzed dehalogenation reaction. The first reaction that was
tested was the reduction of 1-bromoadamantane using 0.1
equiv of tin chloride 2 and NaBH4 as the stoichiometric
reagent (AIBN as the initiator).16a Although a successful
dehalogenation was observed in high yield within 2 h in
refluxing acetonitrile, the phosphonium-supported reagent 4
could not be recovered and recycled because it partly
(12) (a) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. (N.Y.)
1997, 50, 1. (b) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed.
2004, 43, 4704.
(13) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343.
(14) Analysis by ICP-AES of the product indicated that the concentration
in residual tin of the final product was 13 ppm (crude) and <5 ppm (after
flash chromatography).
(9) (a) Enholm, E. J.; Gallagher, M. E.; Moran, K. M.; Lombardi, J. S.;
Schulte, J. P. Org. Lett. 1999, 1, 689. (b) Enholm, E. J.; Schulte, J. P. Org.
Lett. 1999, 1, 1275.
(10) Curran, D. P.; Hadida, S.; Kim, S. Y.; Luo, Z. Y. J. Am. Chem.
Soc. 1999, 121, 6607.
(11) Typically, the tetraarylphosphonium-supported reagents precipitate
well out of a CH2Cl2 solution upon ether addition (ca. e5:1 v/v). With
reagent 2 and 3, hexanes had to be used in significant amounts (ca. 9:1
v/v).
(15) See Supporting Information for typical crude NMR spectra and
further experimental details.
(16) (a) Corey, E. J.; Suggs, J. W. J. Org. Chem. 1975, 40, 2554. (b)
Stork, G.; Sher, P. M. J. Am. Chem. Soc. 1986, 108, 303.
3592
Org. Lett., Vol. 9, No. 18, 2007

decomposed into a phosphine-borane complex and cleaved
tin hydride. However, it should be pointed out that 4 could
be prepared in 89% yield when the chloride 2 was treated
with sodium cyanoborohydride16b in the presence of the
radical inhibitor 2,6-di-tert-butyl-4-methylphenol (BHT).17
In light of these results, a more robust tetraarylphosphonium-
supported tin reagent that would be effective in the tin-
catalyzed dehalogenation reactions was synthesized (Scheme
2). Horner reaction18 of bromoaldehyde 10, anion exchange,
Table 2. Reduction of Halides with Phosphonium-Supported
Tin Hydrides
Scheme 2. Synthesis of Phosphonium-Supported Tin Chloride
13
a
Isolated yield after flash chromatography. b 13 (0.1 equiv), AIBN (0.1
equiv), 3 h. c 13 (0.25 equiv), AIBN (0.1 equiv), 8 h. d 4 (1.2 equiv), AIBN
(0.1 equiv), 6 h.
less reactive aryl bromide 21, a stoichiometric amount of
tin hydride 4 led to the reduced product in excellent yield
(Table 2, entry 7). The phosphonium-supported tin hydride
reagent 14 could be recovered by dissolving the filtered solid
in CH2Cl2. 119Sn NMR analysis showed that the recovered
solid was very clean as it only displayed signals correspond-
ing to the tin hydride reagent.
This observation led us to explore the possibility of
recycling it and reusing it in the dehalogenation reaction of
bromoadamantane (Table 3).
and reduction led to benzyl alcohol 11. A subsequent
treatment of the resulting bromide with vinyl Grignard led
to alkene 12 that underwent hydrostannylation to produce
the desired tin chloride reagent 13. The chemical shift for
the stannane reagent 13 (119Sn NMR (CDCl3) δ 143.9) was
relatively close to that observed for the parent tributyltin
chloride (119Sn NMR (CDCl3) δ 156.5) indicating that this
reagent should simulate the parent compound quite well.
Furthermore, its loading (1.2 mmol/g) is comparable to
polymer supported (0.5-1.5 mmol/g),7b,7e,9b fluorous (0.8
mmol/g),9 and inorganic (0.8 mmol/g) tin reagents.19
Table 3. Recycling of Phosphonium-Supported Tin Hydride 14
Chloride 13 could be converted to the relatively unstable
phosphonium-supported tin hydride 14 upon treatment with
NaBH3CN in the presence of BHT. 1H NMR analysis
indicated the presence of a Sn-H resonance at 4.64 δ ppm.
The reduction of halides using tin chloride 13 proceeded
very well under Stork’s conditions16b (Table 2). Several aryl
and alkyl bromides were converted to the reduced product
in very high yields. After a standard workup, the crude
product was dissolved in CH2Cl2 and the residual tin hydride
14 was precipitated upon hexane addition (5-volume relative
to CH2Cl2). Filtration of the mixture and concentration of
the solution led to a tin-free product.20 In the case of the
run
time (h)
yield (%)a
1
3
3
3
3
4.5
4.5
98
90
96
92
94
90
2b
3b
4b
5b
6b
Determined by GC using decane as the internal standard. b Recovered
tin hydride reagent 14 from the previous entry was used for this entry.
a
Gratifyingly, the tin reagent 14 could be recovered and
recycled up to six times without much lost in its effectiveness
(Table 3). These results are comparable to the best recyclable
polymer-supported organotin7l and fluorous10 organotin
reagents.
(17) The half-life of 4 is ca. 1 day in CD2Cl2 containing traces of BHT.
(18) Horner, L.; Mummenthey, G.; Moses, H.; Beck, P. Chem. Ber. 1966,
99, 2782.
(19) Fu, Q. J.; Steele, A. M.; Tsang, S. C. Green Chem. 2001, 3, 71.
(20) Analysis by ICP-AES of the crude product indicated that the
concentration in residual tin of the final product was 5 ppm (crude).
Org. Lett., Vol. 9, No. 18, 2007
3593

Tin chloride 13 was also used in a radical-mediated
cyclization of iodide 29 (Scheme 3). Treatment of the
Scheme 3. Radical Cyclization Using Stoichiometric Tin
Chloride 13
Figure 1. Phosphonium-supported allyltin reagents.
CH2Cl2, and the tin residues were precipitated upon ether
addition. Filtration and concentration of the filtrate under
reduced pressure led to a tin-free product.23 Although its
synthesis is slightly longer, 33 was a more conveniently
handled solid that precipitated well upon diethyl ether
addition.
Scheme 4. Allylation with Phosphonium-Supported Allyltin
32 and 33
phosphonium-supported tin chloride 13 with NaBH4 gener-
ated a stoichiometric amount of the corresponding tin hydride
that reacted with iodide 29 in the presence of AIBN to
generate silyl ether 30 as a mixture of diastereomers. The
tin byproducts were quantitatively removed by a filtration
following the dilution of the reaction mixture with ether/
hexanes.
NMR analysis of crude 30 did not show the presence of
any tin residues. This material was directly submitted to the
protodesilylation reaction to generate 31 in 77% yield.
The last application of phosphonium-supported tin-medi-
ated reactions that was studied is the Lewis acid mediated
allylation of aldehydes with allyltin reagents.21,22 Both
reagents 32 and 33 (Figure 1) were prepared in 88 and 90%
yield upon treating the corresponding tin chlorides 2 and 13
with allylmagnesium bromide (Et2O/CH2Cl2, -78 °C).
3-Phenylpropionaldehyde (34) was treated with both
reagents in the presence of BF3-OEt2 to produce the desired
homoallylic alcohol in excellent yields (Scheme 4).
Because the products of these allylation reactions were
the corresponding tin alkoxides, an aqueous workup had to
be performed prior to the phase separation process. The crude
product obtained after workup was therefore dissolved in
In conclusion, we have demonstrated that phosphonium-
supported tin reagents provide a general solution for the
removal of tin residues upon product isolation in various
processes. Further work in this area is in progress and will
be reported in due course.
Acknowledgment. This work was supported by NSERC
(Canada), VRQ, Univalor, the Canada Research Chair
Program, and the Universite´ de Montre´al. D.M. is grateful
to NSERC (ES D) for a postgraduate fellowship. We thank
CGC Scientifique (Be´cancour, QC) for the ICP-AES
analyses.
Supporting Information Available: General experimen-
tal procedures. Characterization spectra for new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(21) (a) Naruta, Y.; Ushida, S.; Maruyama, K. Chem. Lett. 1979, 919.
(b) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207.
(22) For supported allyltin reagents, see: (a) Ref 8a. (b) Ref 7j. (c) Cossy,
J.; Rasamison, C.; Pardo, D. G.; Marshall, J. A. Synlett 2001, 629. (d) Cossy,
J.; Rasamison, C.; Pardo, D. G. J. Org. Chem. 2001, 66, 7195. (e) Gastaldi,
S.; Stien, D. Tetrahedron Lett. 2002, 43, 4309. (f) Stien, D.; Gastaldi, S. J.
Org. Chem. 2004, 69, 4464.
OL701447Q
(23) Analysis by ICP-AES of the crude product indicated that the
concentration in residual tin of the final product was 7 ppm.
3594
Org. Lett., Vol. 9, No. 18, 2007