The Diao Group developed a Ni-catalyzed reductive cyclization of 1,6-dienes to form 3,4-disubstituted cyclopentane and pyrrolidine derivatives with high trans-diastereoselectivity. This cyclization reaction enables the efficient synthesis of trans-3,4-dimethyl gababutin, a pharmaceutical lead for treating neuropathic pain, and trans-3,4-dimethylpyrrolidine, a precursor to drug candidates and pesticides. Mechanistic investigation attributes the trans-diastereoselectivity to a classic, organometallic catalytic cycle mediated by Ni(I) and Ni(III) intermediates. This pathway distinguishes this work from previous Ni-catalyzed cross-couplings, where single-electron-transfer mechanism takes place.
The work was accomplished by postdoc Yulong Kuang, in collaboration with graduate students David Anthony and Flaminia Marrucci. Graduate student, Joseph Katigbak, carried out the DFT calculations.
Click here to read the article in Chem.
Click here for more information on Tianning Diao's research group.