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A new approach for the generation and reaction of organotin hydrides: the development of reactions catalytic in Tin

Organotin compounds are versatile reagents in organic chemistry.1 Among the most commonly used tin reagents is tributyltin hydride.2 One of tributyltin hydride’s major applications is in free-radical reactions3 such as dehalogenations of alkyl, vinyl, or aryl halides, often followed by intraor intermolecular C-C coupling. These chain reactions allow the formation of quite complex ring systems and the installation of multiple new stereocenters in one pot. Since these reactions proceed under very mild conditions, a large variety of functional groups is tolerated, avoiding laborious protection and deprotection sequences. Tributyltin hydride has also been used in the reduction of halides, tosylates (via the iodide), thiols, isonitriles, nitrates, and R,â-unsaturated aldehydes (1,4-reduction).4,5 The reagent is also employed in the generation of vinyl stannanes, which are important and useful building blocks in organic synthesis.6,7 Despite the broad applications of organotin hydrides, their utilization is not unproblematic. Tributyltin hydride is relatively expensive, unstable, and toxic. Furthermore, the tin byproducts of its reactions are not always easy to separate and represent an ever increasing disposal problem.8 The invention and development of new methods allowing for the catalytic employment of organostannanes in such reactions would significantly reduce the amount of tin waste and thereby be of great value with respect to both environmental and practical concerns. As such, a specific aim of this research program is the development of reaction procedures that will allow for the in situ generation of organotin hydrides and their subsequent use in organic reactions. Several research groups have investigated reaction methodologies that allow the in situ formation of tin hydride from cheaper starting materials or the employment of catalytic amounts of tin. An early method developed for the in situ generation of tin hydride involved the reduction of tributyltin halides by NaBH4. In fact, in one of the first examples of a reaction catalytic in tin, Corey et al.10 used sodium borane to successfully recycle the tin halide byproduct of a dehalogenation reaction. More recently, Fu et al.11 have developed several elegant methodologies to perform “classical” reactions of tin hydride with only catalytic amounts of tin by using silanes such as polymethylhydrosiloxane (PMHS) to regenerate the tin. However, both of these methods have drawbacks. For example, the use of NaBH4 is not compatible with functional groups susceptible to borohydride or borane reductions. As for the silanes, they do not reduce tin halides, and therefore, their utilization has been limited to the recycling of tin alkoxides. Given such limitations, we believed a mild method that allowed the recycling of tin halides back to tin hydrides would be highly desirable. As fluoride had already been shown to heighten the reducing properties of PMHS,12 we wondered whether polymethylhydrosiloxane (PMHS) made hypervalent by the action of KF13 could efficiently convert tin halides to tin hydrides (Scheme 1). In fact, we found that simply stirring an ethereal solution of Bu3SnCl with 1.1 equiv of PMHS and 2.2 equiv of an aqueous KF solution for 3.5 h, followed by NaOH workup, extraction, and removal of the ether provides Bu3SnH in nearly quantitative yield, albeit with approximately 2-3 mol % of residual PMHS. Distillation of this “crude” material affords analytically pure Bu3SnH in 82% yield. We assume the active species in this reaction to be a hypervalent silane species,13 as neither Bu3SnCl or Bu3SnF reacts with PMHS in the absence of KF.14 However, we have not ruled out the involvement of highly coordinated organotin species in the process.15 In either event, we were interested in determining whether the tin hydride generated under theses conditions could be employed in subsequent in situ chemical transformations. We were pleased to find that our combination of Bu3SnCl, aqueous KF, and PMHS performs well in “classical” tin hydride reactions, such as free-radical dehalogenations. Since tin halides are the byproducts of these reactions, we hoped to be able to recycle them, allowing us to perform these reactions with catalytic amounts of tin. Our results summarized in Scheme 2 demonstrate that we are indeed able to perform these reactions with catalytic amounts of tin. Importantly, we could show in control experiments that the halides are not reduced by the reagent combination PMHS/potassium fluoride, which is known to act as a reducing agent.12,13 Apparently the hypervalent silane alone requires more polar solvents or anhydrous conditions in order to serve as an effective reducing agent. Given our success at free-radical hydrodehalogenations with catalytic amounts of tin hydride, we decided to investigate the reaction of more complex substrates and the possible formation of carbon-carbon bonds. All such reac-