Total Synthesis in the Trost Laboratories: Selected Milestones From the Past Twenty Years

Abstract

Since the early days of his independent career, Prof. Barry M. Trost has maintained a keen interest in complex molecule synthesis. Over the past 55 years, Trost and coworkers have reported syntheses of more than 260 natural products, pharmaceuticals, and other complex biomolecules – a truly extraordinary feat and an incredible testament to Prof. Trost's inventiveness and ingenuity. Even more remarkably, Trost generated more than half of this output – as well as some of his most daring and ambitious syntheses – in just the past twenty years. This review provides a brief summary of all total syntheses from the Trost laboratories since 2000, as well as more detailed vignettes of sixteen particularly notable campaigns, including conquests of callipeltoside A, galanthamine and three related alkaloids, agelastatin A, terpestacin, pseudolaric acid B, ushikolide A, bryostatin 16, laulimalide, aeruginosin 98B, lasonolide A, perophoramidine, leustroducsin B, des‐epoxy‐amphidinolide N, bulleyanaline and three related alkaloids, and bryostatin 3.

Enantioselective Pd‐Catalyzed Allylic Substitution using Phosphite‐Oxazoline PHOX‐Based Ligands containing a Methylene Linker

“…[2] The stereoselectivity comes from an interplay between steric interactions imposed by the chiral cavity of the ligand and the H‐bond and the electrostatic interactions of the amide groups with the nucleophile [3] . Trost ligands represent one of the most effective ligand families and are the ligands of choice for unhindered substrates, being the most widespread applied in total synthesis [1,4] . Another relevant breakthrough arrived with the application of the heterodonor phosphine‐oxazoline PHOX ligands 2 (Figure 1), whose application complemented the Trost ligands, providing high enantioselectivities with hindered substrates and low with narrow ones [5] .…”

“…[3] Trost ligands represent one of the most effective ligand families and are the ligands of choice for unhindered substrates, being the most widespread applied in total synthesis. [1,4] Another relevant breakthrough arrived with the application of the heterodonor phosphine-oxazoline PHOX ligands 2 (Figure 1), whose application complemented the Trost ligands, providing high enantioselectivities with hindered substrates and low with narrow ones. [5] The stereoselectivity is based on the trans influence of the two donor groups that favors the nucleophilic attack predominantly trans to the donor group with the strongest trans influence.…”