Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

Abstract

Herein we report a workflow coupling photoredox-nickel dual-catalyzed N-arylation reactions to benchtop analysis for the efficient generation of fragment-based libraries. Technological advances in photoreactor design facilitated reliable and reproducible experimentation. Knowledge on the reactivity under previously reported reaction conditions of spirocyclic and strained heterocyclic building blocks, viewed as chemistry informers, could thus be rapidly accessed, identifying privileged or challenging scaffolds and paving the way for further exploration.

Nickel‐Photoredox‐Catalyzed Synthesis of sp2−sp3 Fragments and the Impact of Bicycloalkane Isosteric Replacement on Their Physical‐Chemical Properties

“…Given our long‐standing interest in enabling technologies such as photochemistry, [5,6] we then considered the nickel‐photoredox dual‐catalyzed etherification reaction developed by MacMillan , as this strategy occurs at room temperature, using mild bases. The original report used a combination of potassium carbonate and quinuclidine as base, which was less than ideal given the strong basicity of potassium carbonate and the high cost of quinuclidine [7] .…”

Photocatalysis in the Life Science Industry

“…Spirochem reported the use of bespoke photochemical equipment for the rapid investigation of photocatalytic C−N bond coupling reactions of strained amine containing molecules, expediting future syntheses with these building blocks (see section 4.1.2, Scheme 120). 272…”

“…SpiroChem reported the development of a photoreactor that sits on a standard stirrer plate for running up to 10 reactions in parallel using 5 mL crimp top vials. 272 Each reaction is illuminated by an individual 35 W blue LED with watercooling and fans used to dissipate the heat from the highpowered lamp, and an integrated wavelength specific light filter installed to protect users. The reactor was employed, in combination with TLC-MS and benchtop NMR, to enable the synthesis of 29 arylated amines in 4 days via C−N crosscoupling reactions (Scheme 120).…”