Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.

Hydroamination of alkenes catalyzed by transition-metal complexes is an atom-economical method for the synthesis of amines, but reactions of unactivated alkenes remain inefficient. Additions of N–H bonds to such alkenes catalyzed by iridium, gold, and lanthanide catalysts are known, but they have required a large excess of the alkene. New mechanisms for such processes involving metals rarely used previously for hydroamination could enable these reactions to occur with greater efficiency. We report ruthenium-catalyzed intermolecular hydroaminations of a variety of unactivated terminal alkenes without the need for an excess of alkene and with 2-aminopyridine as an ammonia surrogate to give the Markovnikov addition product. Ruthenium complexes have rarely been used for hydroaminations and have not previously catalyzed such reactions with unactivated alkenes. Identification of the catalyst resting state, kinetic measurements, deuterium labeling studies, and DFT computations were conducted and, together, strongly suggest that this process occurs by a new mechanism for hydroamination occurring by oxidative amination in concert with reduction of the resulting imine.