Catalytic and supported Barton-McCombie deoxygenation of secondary alcohols: A clean reaction

Article abstract of DOI:10.1016/S0040-4039(00)00418-4

Secondary alcohols were deoxygenated using a new version of the Barton- McCombie process involving a catalytic amount of supported tin hydride in the presence of trimethoxysilane. The products are then easily separated from the catalyst by a simple filtration avoiding pollution by toxic tin by-products. (C) 2000 ElSevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00418-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3377–3380
Catalytic and supported Barton–McCombie deoxygenation of
secondary alcohols: a clean reaction
Paul Boussaguet,a Bernard Delmond,b Gilles Dumartin a,∗ and Michel Pereyre a
aLaboratoire de Chimie Organique et Organométallique, UMR CNRS 5802, Université Bordeaux I, Bordeaux, France
bLaboratoire de Chimie des Substances Végétales, Institut du Pin, Université Bordeaux I, 351 Cours de la Libération,
33405 Talence Cedex, France
Received 21 January 2000; accepted 10 March 2000
Abstract
Secondary alcohols were deoxygenated using a new version of the Barton–McCombie process involving a
catalytic amount of supported tin hydride in the presence of trimethoxysilane. The products are then easily
separated from the catalyst by a simple filtration avoiding pollution by toxic tin by-products. © 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: deoxygenation; supported reagents; catalytic reaction; tin and compounds; alcohols; clean reaction.
The deoxygenation of secondary alcohols proposed by Barton and McCombie1 is widely used
for the synthesis of bioactive compounds.2–5 Indeed, this method allows a specific deoxygenation of
polyfunctional compounds under mild reaction conditions. The substrate, usually a thionocarbonate or
a xanthate, readily obtained from the secondary alcohol,6 reacts with a tin-centered radical to give an
unstable intermediate which affords, after β-elimination, an alkyl radical rapidly trapped by the tin
hydride, usually tributyltin hydride. Nevertheless, the contamination by organotin compounds, well-
known to be toxic and very difficult to eliminate, is the major drawback of this reaction. In order to
reduce or solve this problem, Fu et al.7 has proposed a method using the tin hydride in a catalytic amount.
Previously, Neumann and Peterseim8 had used a stoichiometric amount of a tin hydride grafted onto an
unsoluble polymer.
We have decided to go one step further by using an unsoluble polymer-supported tin hydride9,10 in
a catalytic amount (Scheme 1). Such a method requires a small quantity of functionalized polymer and
allows easy elimination of the supported tin by-products by simple filtration. Results already reported
show a very low tin pollution level, if any, in the catalytic use of an unsoluble organotin hydride for the
reduction of haloalkanes.10,11
∗
Corresponding author. Fax : 33 5 56 84 66 46; e-mail: g.dumartin@lcoo.u-bordeaux.fr (G. Dumartin)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00418-4
tetl 16698

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Scheme 1. Catalytic and supported variant of Barton–McCombie deoxygenation reaction
The crucial point is the regeneration of the tin hydride from the phenoxytin obtained after the
deoxygenation. Indeed, the use of a reducing agent showing a specific reactivity for phenoxytin and
a neutrality towards the usual organic functions is necessary in order to preserve the high selectivity of
the deoxygenation method. Silanes, and particularly PMHS (polymethylhydrosiloxane), have been used
in tin chemistry because of their ability to rapidly react with Sn–OR bonds12 to give the Sn–H bonds.
Accordingly, Fu et al.7 has shown the utility of PMHS for the formation in situ of the Sn–H bond from
Sn–OPh in the presence of n-BuOH for deoxygenation reactions in homogeneous conditions. However,
the use of PMHS in the presence of a catalytic amount of polymer-supported tin hydride (Scheme 1) gave
poor results, with deoxygenation yields never exceeding 8%. We suppose that the polymeric nature of
this siloxane considerably decreases its diffusion ability into the functionalized polystyrene and prevents
the regeneration of the tin hydride functions. In fact, the low amount of deoxygenated product is only
due to the stoichiometric reaction of the tin hydride initially present.
Thus initially, we have studied the ability of several types of less bulky hydrosil(ox)anes to regenerate
Bu3SnH from Bu3SnOPh13 (Fig. 1). In these homogeneous conditions, only trimethoxysilane afforded
results comparable with those obtained by the use of PMHS.
Next, we used the trimethoxysilane in the Barton–McCombie deoxygenation in the presence of a small
amount of supported tin hydride and the reduction went successfully (Table 1). It seems that, in contrast
to PMHS, the less bulky trimethoxysilane can freely diffuse through the cavities of the polystyrene since
the use of this reducing agent in the catalytic cycle allows completion of the deoxygenations after 24–36
h for three selected substrates.14 The deoxygenation yields are comparable with those obtained in the
classical stoichiometric and homogeneous version using Bu3SnH.
Thanks to the catalytic use of a supported organotin hydride which was proved to be non-polluting,10,11
this new variant of the Barton–McCombie deoxygenation of secondary alcohols seems especially suitable
for applications in the synthesis of biologically active compounds.
References
1. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. 1 1975, 1574–1585.
2. Barton, D. H. R.; Subramanian, R. J. Chem. Soc., Perkin Trans. 1 1977, 1718–1723.
3. Robins, M. J.; Wilson, J. S. J. Am. Chem. Soc. 1981, 103, 932–933.
4. Robins, M. J.; Wilson, J. S.; Hansske, F. J. Am. Chem. Soc. 1983, 105, 4059–4065.
5. Schwartz, R. E.; Hirsch, C. F.; Springer, J. P.; Pettibone, D. J.; Zink, D. L. J. Org. Chem. 1987, 52, 3706–3708.

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Fig. 1. Reduction of phenoxytributyltin by an hydrosil(ox)ane:Bu3SnH formation monitored by gas chromatography. Reaction
conditions: see the general procedure in Ref. 13
Table 1
Deoxygenation with a polymer-supported tin hydride/trimethoxysilane system (Fig. 1). Reaction
conditions: see the general procedure in Ref. 14
6. General procedure for the preparation of thionocarbonates: Phenyl chlorothionocarbonate (1.1 equiv.) was added dropwise
to a solution of the alcohol and pyridine (4 equiv.) (except entry 3: dimethylaminopyridine) in CH2Cl2 (50 mL). After
stirring for 2 h, the reaction mixture was washed with water and extracted with ethyl acetate (3×20 mL). The organic
layers were washed [(i) HCl (1 M); (ii) H2O; (iii) saturated sodium carbonate solution; (iv) brine], dried (MgSO4), and
concentrated. The product was purified by chromatography (silica gel, CH2Cl2).
7. Lopez, R. M.; Hays, D. S.; Fu, G. C. J. Am. Chem. Soc. 1997, 29, 6949–6950.
8. Neumann, W. P.; Peterseim, M. Synlett 1992, 801–802.
9. Ruel, G.; The, N.; Dumartin, G.; Delmond, B.; Pereyre, M. J. Organomet. Chem. 1993, 444, C18–C20.
10. Dumartin, G.; Ruel, G.; Kharboutli, J.; Delmond, B.; Connil, M.-F.; Jousseaume, B.; Pereyre, M. Synlett 1994, 11, 952–954.
11. Dumartin, G.; Pourcel, M.; Delmond, B.; Donard, O.; Pereyre, M. Tetrahedron Lett. 1998, 39, 4663–4666.
12. Itoi, K. French Patent, 1.368.522, 1964.

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13. General procedure for the reduction of phenoxytributyltin under homogeneous conditions: A mixture of phenoxytributyltin,
hydrosil(ox)ane (15 equiv.), n-BuOH (15 equiv.) and toluene was stirred at 80°C under an argon atmosphere. Tributyltin
hydride was monitored by gas chromatography (dodecane as internal reference).
14. General procedure for the deoxygenation of thionocarbonates: A mixture of the thionocarbonate, tin hydride polymer
(1 meq.SnH/g, obtained from Amberlite XE 3059,10 given by Rohm and Haas, 0.1 equiv.), AIBN (0.05 equiv.),
trimethoxysilane (15 equiv.), n-BuOH (16.5 equiv.) and toluene (6 mL) was slowly stirred at 80°C under an argon
atmosphere for 24 h (except entry 3: 36 h) (a new addition of AIBN (0.05 equiv.) was done every 8 h). The solution
was diluted with 10 mL THF, and aqueous NaOH (1 M, 10 mL) was slowly added at room temperature. The reaction
mixture was stirred for 4 h, filtered to eliminate the supported catalyst and extracted with Et2O (3×10 mL). The organic
layers were washed [(i) HCl (1 M); (ii) H2O; (iii) brine], dried (MgSO4), and concentrated. The product was purified by
flash cromatography (silica gel, petroleum ether) (except entry 3: petroleum ether:Et2O, 90:10).