Evolution of synthetic routes towards homochiral Tapentadol

Analysis of the literature shows that the development of synthetic approaches to Tapentadol, an agonist of the μ-opioid receptor and norepinephrine reuptake inhibitor, has followed four, partially overlapping, phases. The most advanced approaches, based on stereoselective syntheses, appeared only after 2010. The majority of the chemistry examples presented in this review come from patent applications and as such have not been subjected to rigorous peer review, but may serve well as an inspiration to organic chemists for solving analogous synthetic problems.