UCLA organic chemistry laboratories led by Distinguished Professors Neil Garg and Ken Houk have reported a groundbreaking study in Nature.
The groups demonstrate that two highly strained reactants, a cyclic allene and a bicyclobutane, undergo coupling at room temperature through a sigma-bond insertion reaction. “This stepwise s + p cycloaddition is unique because it does not require the usual thermal or transition metal activation often required for such reactions,” said Houk.
The authors show that the significant geometric distortion of the reactants leads to each having innate diradical character. The authors suggest that this ‘diradicaloid’ property is essential for the success of their newly discovered reaction and propose that diradicaloids can be further exploited in synthetic chemistry following their studies.
“The products formed are likely to be extremely valuable for drug discovery efforts,” added Garg, who noted the growing popularity of bicyclohexanes, the motif accessed in this study, in medicinal chemistry.
This latest report is the 30th collaborative publication between the Garg and Houk laboratories and marks a noticeable advancement in their joint studies of strained intermediates. Prior to this effort, the groups shared the 2024 Royal Society of Chemistry Horizon Perkin Prize in Physical Organic Chemistry “for the creative advancement of strained intermediates involving cumulated cyclic dienes and trienes ” and published a landmark study on elusive anti-Bredt olefins in Science Magazine in 2024.
The researchers in the Garg and Houk laboratories who completed the experiments and computations are Garg lab graduate students Arismel Tena Meza, Christina Rivera, and Andrew Kelleghan, and Houk Laboratory Teacher-Scholar, Adjunct Assistant Professor Huiling Shao.
For more information, contact Professors Neil Garg (neilgarg@ucla.edu) and Ken Houk (houk@chem.ucla.edu).
