Martin D. Eastgate

Enantioselective oxygenation of unactivated C(sp³)-H bonds via asymmetric metalation remains an unsolved challenge. Herein we report the development of a Pd-catalyzed, enantioselective C(sp³)-H tosylation of native amides with NaOTs as the nucleophile, representing a rare example of enantioselective C-H functionalization with a nucleophilic coupling partner. High enantioselectivity in this reaction is achieved by chiral monoprotected amino sulfonamide (MPASA) ligands. Substantial enhancement of the enantioselectivity by silver salt additives was also observed. Through desymmetrization of the readily available isopropyl moiety, structurally diverse β-tosylated amides bearing an α-methyl stereocenter were obtained with high yield and enantioselectivity, which complements the current enzymatic method for making Roche ester chiral synthon. The tosylated products are highly versatile chiral building blocks for further diversifications with nitrogen, oxygen, and other nucleophiles, thus providing a platform for constructing chiral methyl stereocenters.

The first practical, fully stereoselective P(V)-radical hydrophosphorylation is presented herein by using simple, limonene-derived reagent systems. A set of reagents have been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products, which can be further diversified (with conventional 2e^- chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity, and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.

The first practical, fully stereoselective P(V)-radical hydrophosphorylation is presented herein using simple, limonene-derived reagent systems. A set of reagents has been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products which can be further diversified (with conventional 2e- chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.

A flurry of recent research has centered on harnessing the power of nickel catalysis in organic synthesis. These efforts have been bolstered by contemporaneous development of well‐defined nickel (pre)catalysts with diverse structure and reactivity. In this report, we present ten different bench‐stable, 18‐electron, formally zero‐valent nickel–olefin complexes that are competent pre‐catalysts in various reactions. Our investigation includes preparations of novel, bench‐stable Ni(COD)(L) complexes (COD=1,5‐cyclooctadiene), in which L=quinone, cyclopentadienone, thiophene‐S‐oxide, and fulvene. Characterization by NMR, IR, single‐crystal X‐ray diffraction, cyclic voltammetry, thermogravimetric analysis, and natural bond orbital analysis sheds light on the structure, bonding, and properties of these complexes. Applications in an assortment of nickel‐catalyzed reactions underscore the complementary nature of the different pre‐catalysts within this toolkit.