Hydroaminomethylation of Natural Allylic and Homoallylic Alcohols: A Ligand-Controlled Route to New Amines

Hydroaminomethylation (HAM) is a tandem catalytic process that allows accessing amines from olefin scaffolds and is perfectly aligned with green chemistry precepts. In this work, HAM was applied to the natural hydroxyolefins: isoprenol, linalool, nerolidol, and isopulegol. Employing 4-methylpiperidine, morpholine, and 1,2,3,4-tetrahydroisoquinoline as counterparts, several new, structurally complex amines were prepared from biorenewable, low-cost substrates, opening a path to exploit this structure diversity in biological activity. By the appropriate choice of rhodium-based catalytic systems, as well as the reaction conditions, the necessary fine tuning for each counterpart was achieved. The unpromoted rhodium system leaded mostly to aminoalcohols, while certain phosphorus(III)-promoted rhodium systems afforded amines containing a tetrahydropyran or a tetrahydrofuran moiety in moderate to high yields.