A practical method for the removal of organotin residues from reaction mixtures

Full text of DOI:10.1021/jo960751c

7200
J . Org. Chem. 1996, 61, 7200-7201
removed from the crude product by oxidative conversion
A P r a ctica l Meth od for th e Rem ova l of
to polymeric, insoluble tin fluorides15 by coordination to
an amine prior to silica gel chromatography16 and, for
polar compounds, by partitioning between acetonitrile
and a hydrocarbon solvent.17 Finally, several protocols
have been developed for the use of a catalytic quantity
of an organotin reagent with recycling in situ by means
of borohydride18 or silane reagents.19 Consideration of
the various catalytic tin methods suggested that many
R3SnX species must be very rapidly reduced by boro-
hydrides and silanes to R3SnH. Indeed, Curran and co-
workers have reported that NaBH3CN reduces Bu3SnCl
in t-BuOH rapidly and quantitatively in a few minutes
at room temperature.20 Moreover, Bu3SnH and Ph3SnH
are very nonpolar compounds that can be washed rapidly
from silica gel with hydrocarbon eluants. It was appar-
ent, therefore, and readily demonstrated, that for a wide
variety of organotin-mediated reactions, a brief boro-
hydride treatment of the crude reaction mixtures should
greatly facilitate purification.
In an initial experiment, 9,10-dibromoanthracene (1)
was reduced with Bu3SnH and AIBN in benzene at
reflux. After concentration, NaBH3CN and t-BuOH were
added and the mixture heated to reflux for 1 h. After a
further concentration the reaction mixture was applied
to a silica gel column and eluted with hexanes when Bu3-
SnH was recovered quantitatively. Further elution with
hexane/benzene (1:1) yielded analytically pure an-
thracene, also quantitatively (Table 1, entry 1). In a
second experiment, 4,4′-dimethoxytrityl chloride (DMT-
Cl, 3) was reduced with Bu3SnH and the crude reaction
mixture treated with NaBH3CN. After a brief aqueous
wash, the reduction product was recovered free of tin
residues by filtration on silica gel (Table 1, entry 2).
Further examples covering a range of different tin
hydride-mediated reductions, classes of substrate, and
functionality are presented in Table 1. In each case, the
tin hydride could be recovered in excellent yield and the
1H-NMR spectrum of the product, as eluted from the
column, revealed the absence of organotin contaminants.
Control experiments in which the borohydride treatment
was omitted led to the isolation of products with consid-
erable tin contamination (supporting information). We
draw special attention to entry 6 of Table 1 in which a
hydrocarbon was obtained free of organotin residues by
the simple expedient of replacing the coeluting Bu3SnH
by the slightly more polar Ph3SnH.21
Or ga n otin Resid u es fr om Rea ction
Mixtu r es
David Crich* and Sanxing Sun
Department of Chemistry, University of Illinois at Chicago,
845 West Taylor Street, Room 4500,
Chicago, Illinois 60607-7061
Received April 24, 1996
Due to the combination of availability, stability, func-
tional group compatibility, convenient rate constant for
hydrogen atom donation to alkyl radicals, and excellent
chain carrying properties of stannyl radicals, preparative
free radical chemistry is dominated by the use of orga-
notin hydrides (Bu3SnH and Ph3SnH).1 Unfortunately,
the triorganotin halide, chalcogenide, and alkoxide byprod-
ucts from these reactions show a tendency to hydrolyze
slowly on silica gel, which frequently renders purification
difficult. This problem, which is particularly prominent
in the pharmaceutical industry when such impurities
resulting from say the Barton deoxygenation2 of an
aminoglycoside antibiotic must be reduced below the
trace level, also extends to the one-3 and two-electron4
reactions of allylstannanes and to the use of organotin
halides as Lewis acids.5
Numerous approaches have been adopted to circum-
vent this problem. Alternative reagents have been
devised and are successful to varying degrees; for ex-
ample, Bu3SnH may be replaced in the Barton deoxy-
genation by hypophosphorous acid6 or by thiol/silane
couples7 and in the Barton decarboxylation by mercap-
tans,8 but none, with the possible exception of tris(tri-
methylsilyl)silane,9 are as general or have all the at-
tributes of the tin hydrides. The use of water-soluble tin
hydrides,10 as well as those bearing polar groups to assist
purification,11 has much promise but is not widely applied
perhaps due to commercial inavailability. Current poly-
mer-supported tin hydrides suffer from poor recyclabil-
ity.12 The fluorous organotin reagents recently described
by the Curran group,13 combined with extraction into an
immiscible fluorous phase, show considerable promise,
as do the ingenious allylstannylamines developed by
Pereyre and co-workers.14 When the use of Bu3SnH or
Ph3SnH is mandated, organotin byproducts may be
(1) (a) Neumann, W. P. Synthesis 1987, 665. (b) Pereyre, M.;
Quintard, J .-M.; Rahm, A. Tin in Organic Synthesis; Butterworths:
London, 1987. (c) J asperse, C. P.; Curran, D. P.; Fevig, T. L. Chem.
Rev. 1991, 91, 1237.
(2) Barton, D. H. R.; McCombie, S. W. J . Chem. Soc., Perkin Trans.
1 1975, 1575.
(3) Keck, G. E.; Enholm, E. J .; Yates, J . B.; Wiley, M. R. Tetrahedron
1985, 41, 4079.
(4) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(5) Sibi, M. P.; J i, J . J . Am. Chem. Soc. 1996, 118, 3063.
(6) Barton, D. H. R.; J ang, J . O.; J aszberenyi, J . Cs. J . Org. Chem.
1993, 58, 6838.
The present protocol, involving stoichiometric use of
of a triorganostannane followed by a borohydride workup,
has clear advantages over the widely used catalytic
stannane protocol with in situ regeneration by boro-
hydrides in certain instances. Thus, application of the
Stork protocol to 9 resulted in the complete consumption
of the substrate but the formation of 0% of 10 (cf. Table
1, entry 5). This is readily understood in terms of the
instability of 9 under the reaction conditions. In the case
(7) Cole, S. J .; Kirwan, J . N.; Roberts, B. P.; Willis, C. R. J . Chem.
Soc., Perkin Trans. 1 1991, 103.
(8) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron 1985,
41, 3901.
(15) (a) Leibner, J . E.; J acobus, J . J . Org. Chem. 1979, 44, 449. (b)
Barton, D. H. R.; Motherwell, W. B.; Stange, A. Synthesis 1981, 743.
(16) Curran, D. P.; Chang, C. T. J . Org. Chem. 1989, 54, 3140.
(17) Berge, J . M.; Roberts, S. M. Synthesis 1979, 471.
(18) (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.
(19) Hays, D. S.; Fu, G. C. J . Org. Chem. 1996, 61, 4.
(20) Curran, D. P.; Shen, W. J . Am. Chem. Soc. 1993, 115, 6051.
(21) In this one case, as indicated by the control experiment, the
borohydride treatment was unnecessary. This is readily understood
in terms of the hydrocarbon nature of 10 and its elution from silica
gel ahead of any triarylorganotin derivatives.
(9) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188.
(10) (a) Light, J .; Breslow. R. Tetrahedron Lett. 1990, 31, 2957. (b)
Rai, R.; Collum, D. B. Tetrahedron Lett. 1994, 35, 6221.
(11) Clive, D. L. J .; Yang, W. J . Org. Chem. 1995, 60, 2607.
(12) (a) Gerlach, M.; J o¨rdens, F.; Kuhn, H.; Neumann, W. P.;
Peterseim, M. J . Org. Chem. 1991, 56, 5971. (b) Neumann, W. P.;
Peterseim, M. React. Polym. 1993, 20, 189.
(13) Curran, D. P.; Hadida, S. J . Am. Chem. Soc. 1996, 118, 2531.
(14) Fouquet, E.; Pereyre, M.; Roulet, T. J . Chem. Soc., Chem.
Commun. 1995, 2387.
S0022-3263(96)00751-7 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 20, 1996 7201
Ta ble 1.
% yield
substrate
R3SnH
treatment
product
anal. calcd
anal. found
% R3SnH recovered
1
3
5
7
9
Bu3SnH
Bu3SnH
Bu3SnH
Bu3SnH
Ph3SnH
NaBH3CN
NaBH3CN
NaBH4
NaBH3CN
NaBH3CN
2
4
6
8
10
100
100
95
84
83
C, 94.35; H, 5.66
C, 82.87; H, 6.62
C, 50.60; H, 6.07
C, 83.94; H, 10.73
C, 84.82; H, 15.18
C, 94.23; H, 5.61
C, 82.92; H, 6.73
C, 50.67; H, 6.03
C, 83.81; H, 10.61
C, 84.90; H, 15.17
100
97
95
83
81
stirred for 5 min at room temperature. After evaporation of the
volatiles, the crude product was extracted with dichloromethane,
and the extracts were purified by preparative TLC (eluent:
hexane:ethyl acetate ) 1:1) to afford Bu3SnH (77.4 mg, 95%)
and 624 (59.3 mg, 95% yield) free from organotin residues as
demonstrated by 1H-NMR spectroscopy.
S-Meth yl O-(3â-p r egn -5-en -20-on yl) d ith ioca r bon a te (7)
was prepared in the standard manner:2 mp 160-170 °C dec; 1H-
NMR δ 0.59 (3 H, s), 0.97 (1 H, m), 1.02 (3 H, s), 1.15 (3 H, m),
1.35-1.75 (9 H, m), 1.90 (1 H, m), 1.90-2.20 (4 H, m), 2.10 (3
H, s), 2.45 (2 H, m), 2.50 (3 H, s), 5.35 (2 H, m); 13C-NMR δ
13.1, 18.7, 19.2, 20.9, 22.7, 24.4, 27.0, 31.4, 31.7, 36.5, 36.8, 37.3,
38.7, 42.2, 43.8, 49.7, 56.7, 83.2, 122.8, 139.1, 209.2, 214.9. Anal.
Calcd for C23H34O2S2: C, 67.93; H, 8.43. Found: C, 68.35; H,
8.84.
P r egn -5-en -20-on e (8). A solution of 7 (156.3 mg, 0.384
mmol), Bu3SnH (153.0 µL, 0.576 mmol), and AIBN (12.6 mg,
0.077 mmol) in toluene (6 mL) was heated at reflux for 4 h. After
concentration, NaBH3CN (72.5 mg, 1.15 mmol) and t-BuOH (8
mL) were added, and the mixture was stirred at room temper-
ature for 2 h. After evaporation of the volatiles, the crude
product was extracted with dichloromethane, and the extracts
were purified by preparative TLC (eluent: hexane:ethyl acetate
) 6:1) to give Bu3SnH (139 mg, 83%) and 825 (97.0 mg, 84%)
free from organotin residues as demonstrated by 1H-NMR
spectroscopy.
P en ta d eca n e (10). A solution of 926 (91.0 mg, 0.204 mmol),
Ph3SnH (143.0 mg, 0.41 mmol), and AIBN (17 mg, 0.1 mmol) in
xylenes (4 mL) was heated at reflux for 20 h. Further portions
of Ph3SnH (143.0 mg, 0.41 mmol) and AIBN (17 mg, 0.1 mmol)
were added after 5 and 10 h. After concentration, NaBH3CN
(120.0 mg, 1.91 mmol) and t-BuOH (10 mL) were added, and
the mixture was heated to reflux for 0.5 h. After evaporation of
the volatiles, the crude product was extracted with dichlo-
romethane, and the extracts were purified by column chroma-
tography on silica gel (eluent: hexane) to give Ph3SnH (347.5
mg, 81%) and 10 (36.0 mg, 83%) free from organotin residues
as demonstrated by 1H-NMR spectroscopy.
of 5, the catalytic protocol resulted in the isolation of
mixtures of 6 and the migration product 1124 (cf. Table
1, entry 3) owing to the low concentration of tin hydride
in the reaction mixture.
Finally, we note that this new workup protocol permits
recovery in very high yield, and thus recycling, of the
triorganotin hydride, with obvious economic and envi-
ronmental implications for large scale work.
Exp er im en ta l Section 22
An th r a cen e (2). A solution of 1 (1.0 g, 2.98 mmol), Bu3SnH
(1.74 mL, 6.55 mmol), and AIBN (98.0 mg, 0.60 mmol) in
benzene (60 mL) was heated at reflux for 6 h. After concentra-
tion to half volume NaBH3CN (0.37g, 5.95 mmol) and t-BuOH
(25 mL) were added, and the mixture was heated to reflux for 1
h. Concentration and column chromatography on silica gel
(eluent: hexane f hexane:benzene ) 1:1) afforded Bu3SnH (1.91
g, 100% recovery) and 2 (0.53 g, 100%) free from organotin
residues as demonstrated by 1H-NMR spectroscopy.
Bis(p-m eth oxyp h en yl)p h en ylm eth a n e (4). A solution of
3 (1.0 g, 2.95 mmol), Bu3SnH (0.86 mL, 3.25 mmol), and AIBN
(24.0 mg, 0.15 mmol) in benzene (30 mL) was heated at reflux
for 12 h. NaBH3CN (0.21 g, 3.34 mmol) and t-BuOH (30 mL)
were then added and the reflux continued for 30 min. After
cooling, the solution was washed with saturated aqueous sodium
bicarbonate and dried with sodium sulfate. Concentration and
column chromatography on silica gel (eluent: hexane f hexane:
ethyl acetate ) 10:1) afforded Bu3SnH (0.92 g, 97%) and 4 (0.89
g, 100%) free from organotin residues as demonstrated by 1H-
NMR spectroscopy.
Ack n ow led gm en t. We thank the National Science
Foundation for support of this work (CHE-9625256).
D.C. is a Fellow of the A. P. Sloan Foundation.
Su p p or tin g In for m a tion Ava ila ble: 1H-NMR spectra of
2, 4, 6, 8, and 10 as isolated by silica gel chromatography
showing absence of organotin residues and the corresponding
spectra from the control experiments omitting the borohydride
treatment (10 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
2,3,4,6-Tetr a -O-a cetyl-1-d eoxy-D-glu cose (6). A solution
of 523 (91.0 mg, 0.188 mmol), Bu3SnH (74.2 µL, 0.28 mmol), and
AIBN (6.2 mg, 0.04 mmol) in benzene (3 mL) was heated at
reflux for 4 h. After concentration to dryness, NaBH4 (8.0 mg,
0.21 mmol) and EtOH (4 mL) were added, and the mixture was
J O960751C
(24) Beckwith, A. L. J .; Duggan, P. J . J . Chem. Soc., Perkin Trans.
2 1993, 1673.
(22) For general experimental procedures see: Crich, D.; Sun, S.;
Brunckova, J . J . Org. Chem. 1996, 61, 605.
(23) Bonner, W. A.; Robinson, A. J . Am. Chem. Soc. 1950, 72, 354.
(25) Gonzalez, M. D.; Burton, G. Z. Naturforsch. 1985, 40b, 639.
(26) Barton, D. H. R.; Crich, D.; Kretzschmar, G. J . Chem. Soc.,
Perkin Trans. 1 1986, 39.