Recent Nature publication by Houk and Garg groups featured in Chemical & Engineering News (C&EN).
The research team of Liana Hie, CalTech postdoc Dr. Noah Fine Nathel (former Garg Group student), Tejas Shah, Emma Baker (Garg Group), Dr. Xin Hong, Dr. Yun-Fang Yang (Houk Group), University of Pittsburgh Prof. Peng Liu (former Houk Group postdoctoral scholar), Prof. Ken Kouk and Prof. Neil Garg, reported on their development of a nickel-catalyzed method for cleaving the typically unreactive amide functional group in their paper published in the journal Nature. Their research was highlighted recently in Chemical & Engineering News (C&EN).
The research team Liana Hie, Dr. Noah Fine Nathel, Tejas Shah, Emma Baker, Dr. Xin Hong, Dr. Yun-Fang Yang, Prof. Peng Liu, Prof. Ken Houk, Prof. Neil Garg
Excerpt from “Chemists Find a Simple Approach to Activating Amide C-N Bonds” in Chemical and Engineering News (C&EN) (By Stephen K. Ritter)
Nature typically outdoes chemists when it comes to efficiently carrying out reactions. But for a nickel—or make that a simple nickel catalyst—a team of UCLA chemists has matched wits with enzymes on cleaving the C–N bond in amides. The achievement overcomes a classic problem of the low reactivity of amides and opens up this key family of compounds to broader use as synthetic building blocks. Amides are the functional units that link amino acids together in proteins and are present in a range of natural and synthetic molecules. Some enzymes such as proteases have evolved to bind and cleave amide bonds, a process that governs many regulatory functions in cells and is responsible for degrading proteins to amino acids. But the double-bond resonance running through the O–C–N unit of amides makes the molecules poor electrophiles. They are therefore unreactive toward alcohol nucleophiles in all but the harshest conditions and with excessive amounts of reagents. UCLA’s Kendall N. Houk, Neil K. Garg, and their coworkers, who carried out the research, say it’s surprising that chemists have never found a simple way to catalytically cleave amide acyl C–N bonds in the lab. That’s despite the fact that chemists carry out many precious-metal-catalyzed reactions on molecules containing amide linkages. To take a more focused look at the problem, the team used a combination of computational and experimental studies, allowing them to develop a nickel catalyst system that makes short work of amide bonds.
In a series of test cases, the researchers used the new methodology to combine a variety of amides and alcohols to make esters and amines, including tricky situations in which the reactants already contained potentially competing functional groups and stereocenters (
Read full C&EN Article here.
To learn more visit the Garg Group and Houk Group homepages.