Contemporary screening approaches to reaction discovery and development

Abstract

New organic reactivity has often been discovered by happenstance. Several recent research efforts have attempted to leverage this to discover new reactions. In this Review, we attempt to unify reported approaches to reaction discovery on the basis of the practical and strategic principles applied. We concentrate on approaches to reaction discovery as opposed to reaction development, though conceptually groundbreaking approaches to identifying efficient catalyst systems are also considered. Finally, we provide a critical overview of the utility and application of the reported methods from the perspective of a synthetic chemist, and consider the future of high-throughput screening in reaction discovery.

Nickel: The “Spirited Horse” of Transition Metal Catalysis

“…[10][11][12][13][14][15]16 Diverse reactivity and cost-efficiency provided a valuable driving force for the remarkable progress of nickel catalysts in this area, 17 with more challenges coming in the modern design of process equipment. 18,19 Further development of the field involved rapid progress in Ni-catalyzed C-X cross-coupling reactions 20,21,22 and the MizorokiHeck reaction. 23 The utility of very simple catalyst precursors, such as Ni(acac) 2 , in a variety of transformations deserves special mention.…”

Fulfilling the promise of the materials genome initiative with high-throughput experimental methodologies

“…The deep roots and continued prevalence of HTE in pharmaceutical research enable efficient exploration for small molecule functionalization in medicinal chemistry 91 and reaction discovery in synthetic chemistry. 92 Due to the role that molecular structure plays in facilitating a chemical reaction, structure-activity relationships are prevalent in small molecule catalysis and motivate integration of HTE methods with descriptor-based catalyst design from statistical or theoretical computation. 93 Indeed, a hallmark achievement in the catalysis field resulted from a Dow Chemical Corporation computation-guided HTE program that yielded the now industrialized process for synthesizing InFuse TM olefin block copolymers (OBCS).…”

Automatic discovery and optimization of chemical processes

“…A significant departure from this approach is the use of dedicated robotic experimental systems, which could either involve parallel batch or flow experiments. Such systems are developed for high-throughput experiments and enable rapid discovery of new reactions [22,23,24 ], or optimization of process conditions of known reactions [25,26]. A flow array system has been used to discover a new inorganic cluster [7 ].…”