A new class of catalysts consisting of small organic molecules with a "key" proton embedded in their structure can produce amines and alchohols with enantioselectivities of 92% or more, according to a team of researchers at Boston College, Chestnut Hill, Mass.
The catalysts are derived from the abundant and renewable amino acid valine, and can be synthesized in four steps using inexpensive, readily available materials, note the researchers. The proton plays a key role in achieving the high enantioselectivity, as well as "unprecedented" rates of catalyst regeneration and product release, they add. Using as little as 0.25% catalyst with organoboron reagents and imines and carbonyls, the researchers produced amines and alcohols at yields of greater than 85% in less than six hours at room temperature — with an enantiomeric ratio (e.r.) of 97:3 or more. The amines and alcohols can be used to prepare biologically active molecules. More details appear in a recent article in Nature."A reaction that can be initiated by a minute amount of readily accessible and inexpensive catalyst to afford valuable organic molecules with high selectivity and which requires only renewable resources, as opposed to precious and rate elements, is extremely important to future advances in medicine and the life sciences," contends Amir Hoveyda, a professor of chemistry at the college."The catalyst turnover and product release are exceptionally fast for a catalyst that does not have a metal center and thus does not enjoy the tremendous advantages that facile ligand exchange offers organometallic systems. We gain the same advantage by the embedded proton, as we describe in the [Nature] paper," he says.In addition, the system can easily favor either enantiomer. "We can just use the other enantiomer of valine to prepare the catalyst," he adds. Robustness of the catalyst and susceptibility to poisoning are not concerns, he notes. However, key challenges remain, including making the reaction gamma-selective, and altering the catalyst so that H-bonding sites aren't required.The next step involves trying additional organoboron reagents, classes of imines and carbonyls, as well as working towards a more in-depth mechanistic understanding. "There is a substantial area of reactivity/selectivity space that these catalysts are capable of filling and we have had several exciting findings since we submitted our paper to Nature. I am not sure optimizing 97:3 e.r. values any further is the best way to spend our time and funds; at some points improving selectivity becomes a matter of reaction engineering versus furthering the science," Hoveyda contends.Larger-scale testing is imminent; two vendors have approached Hoveyda about licensing the catalyst and scaling up the synthesis will take a few months.Hoveyda also has worked on a new way to produce Z alkenes using a molybdenum-based catalyst (see "Method Makes Z Alkenes").