Simple Organic Molecules as Catalysts for Enantioselective Synthesis of Amines and Alcohols

The discovery of new catalysts that can generate complex organic compounds via enantioselective transformations is central to advances in the life sciences;(i) for this reason, many chemists try to discover catalysts that can be used to produce chiral molecules with a strong preference for one mirror image isomer.(ii) The ideal catalyst should be devoid of precious elements(iii) and should bring reactions to completion in a few hours using operationally simple procedures. In this manuscript, we introduce a set of small organic molecules that can catalyze reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which can be used to synthesize more complex, biologically active molecules. A distinguishing feature of this new catalyst class is the presence of a 'key' proton embedded within their structure. The catalyst is derived from the abundant amino acid valine and was prepared in large quantities in four steps using inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mol % catalyst in less than six hours at room temperature to generate products in >85% yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents render this advance vital to future progress in chemistry, biology and medicine.