Houk/Garg collaboration study of cyclic allenes reported in Nature is highlighted in Chemical & Engineering News

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In the journal Nature, the Garg and Houk groups report the use of unusual strained intermediates in asymmetric catalysis, work highlighted in C&EN.  “Intercepting fleeting cyclic allenes with asymmetric nickel catalysis”, was published in the August 26, 2020 issue of Nature. The discoveries were made by experimentalists in Professor Neil Garg’s lab, former and current graduate students Michael Yamano (now a Senior Associate Scientist at Amgen), Andrew Kelleghan, and Bryan Simmons (now a Scientist at Bristol-Myers Squibb), and postdoc Maude Giroud, teaming up with computational chemists in Professor Ken Houk’s lab, visiting undergraduates from Nankai and Tianjin Universities in China, Qianzhen Shao and Bo Li, with former Cram Teacher-Scholar and postdoc, Shuming Chen, now a professor at Oberlin College.  “This remarkable team of chemists in our groups was able to create some truly innovative and useful chemistry and to figure out a remarkably complex mechanism as well,” said Houk.


Chemical & Engineering News

 – September 4, 2020 (by Leigh Krietsch Boerner):
HoukGarg Nature

Snagging the power of cyclic allene intermediates

Coupled with a catalyst, strained compounds can control chirality

HoukGarg Nature2Strained cyclic compounds have long been curiosities in organic chemistry, but chemists have not explored many ways to harness their reactivity. Although cyclic allenes racemize spontaneously, chemists have been able to take stereoselective control over the mixtures, but only by using large amounts of chiral compounds. A new study shows that chemists can catalytically take advantage of this process to build stereospecific complexity into target organic compounds, which are useful in agrochemistry and drug development. Neil Garg, Kendall Houk, and coworkers at the University of California, Los Angeles, have managed to grab strained cyclic allene intermediates and use them in catalytic asymmetric reactions to make tricyclic lactams of mainly one enantiomer (Nature 2020, DOI: 10.1038/s41586-020-2701-2).The team reacted a benzyl triazinone and a cyclic allene precursor in the presence of a nickel catalyst with an iron cyclopentadienyl-based chiral ligand to give two intermediates: a strained cyclic allene and an organometallic intermediate based on the Ni catalyst. These species quickly merge to form a chiral adduct through olefin insertion, to give the product (shown) an as high as 85% yield and 94% enantiomeric purity. Garg and coworkers crystallized the product and found that the reaction makes the opposite enantiomer—not the one they expected. Through calculations, they found that the transition state leading to the favored enantiomer forms through stabilization from the solvent, making it slightly lower in energy. This research shows that strained intermediates can be used to make highly enantiomerically pure compounds, Garg says.

Image above right: A 3-D view of a cyclic allene Credit: QR Chem

——————————– Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.