Recent Progress on One-Pot Multisubstrate Screening

Abstract

Traditionally, new synthetic reactions have been developed using a model substrate to screen reaction conditions before testing the optimized conditions with a range of more complex substrates. In 1998, Gao and Kagan pooled multiple substrates in one pot to study the generality of an enantioselective method. Although such one-pot multisubstrate screenings may be powerful, few applications have appeared in the literature. With the advancement of various chromatography techniques, it may be time to revisit this underutilized platform. This review article discusses the applications of one-pot multisubstrate screenings as a method for developing new synthetic methods.

Late-Stage C–H Deuteration of Organic Compounds via Ligand-Enabled Palladium-Catalyzed Hydrogen Isotope Exchange

“…In order to avoid the tedious work associated with conducting various extensive optimization campaigns, we turned our attention to the efficient yet underutilized strategy of multi-substrate screening. 38 This approach was first introduced in 1998 by Gao and Kagan 39 and by Jackson et al 40 in asymmetric catalysis as an efficient alternative to high throughput experimentation. Despite its efficiency, this ap-…”

Pd(II)-Catalyzed Nondirected Late-Stage C(sp2)–H Deuteration of Heteroarenes Enabled Through a Multi-Substrate Screening Approach

“…This strategy was introduced in 1998 independently by Gao and Kagan, [18] and Jackson et al [19] as a means to efficiently optimize the stereoselectivity of a reaction for a broad scope of substrates. [20,21] Here, multiple substrates, ideally covering the whole range of properties expected in the scope of the method, are combined in one reaction vessel during the optimization campaign. At the same time the number of substrates should remain small enough to ensure reproducibility and reliable analytics.…”

Palladium(II)‐Catalyzed Nondirected Late‐Stage C(sp2)−H Deuteration of Heteroarenes Enabled Through a Multi‐Substrate Screening Approach

“…This strategy was introduced in 1998 independently by Gao and Kagan, [18] and Jackson et al [19] as a means to efficiently optimize the stereoselectivity of a reaction for a broad scope of substrates. [20,21] Here, multiple substrates, ideally covering the whole range of properties expected in the scope of the method, are combined in one reaction vessel during the optimization campaign. At the same time the number of substrates should remain small enough to ensure reproducibility and reliable analytics.…”

“…Following these seminal reports, the method was almost exclusively adopted in asymmetric catalysis. [20,21] The approach has also been used to obtain scope information or mechanistic information for existing synthetic methods. [22] Furthermore, Plenio used multi-substrate screening to optimize the reaction conditions of Sonogashira reactions.…”