The Radical-Based Reduction with (TMS)₃SiH ‘On Water’

Abstract

Reduction of different organohalides, bromonucleosides among them, was successfully carried out in yields ranging from 75% to quantitative, using (TMS)₃SiH in a heterogeneous system with water as the solvent. Our procedure, employing 2-mercapto­ethanol as the catalyst and the hydrophobic diazo-compound ACCN as the initiator, illustrates that (TMS)₃SiH can be the radical-based reducing agent of choice in aqueous medium. (TMS)₃SiH does not suffer from any significant reaction with water and can safely be used with additional benefit, such as ease of purification and en­vironmental compatibility.

radical reactions - reductions - tris(trimethylsilyl)silane - azo compounds - thiols

References

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Visiting scientist. Permanent address: University of Belgrano-Conicet, Villanueva 1324, 1426 Buenos Aires, Argentina.

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14

General Experimental Procedure.
In a 5-mL screw-cap Wheaton vial equipped with a magnetic stirrer, a heterogeneous mixture of halogenated substrate (0.05 mmol, 10 mM), tris(trimethylsilyl)silane (18.5 µL, 0.06 mmol, 12 mM) and 2-mercaptoethanol (1 µL, 0.014 mmol, 2.85 mM) was prepared in H₂O (0.5 mL). The mixture was deoxygenated with a slow stream of argon for 10 min. The initiator was added and the vial was placed in a thermostatically controlled metal rack at the desired temperature (see Table [1] ). The reaction was monitored by HPLC analysis at different times, and the products were recognized by comparison with commercial references. For product isolation, after extraction by n-hexane, the aqueous phase contained the reduced product, which can be further purified by reverse-phase column chromatography. The procedure was also performed on a 10-fold scale with similar results.