Challenges and Opportunities in Multicatalysis

Abstract

Multi-catalysis is an emerging field targeting the development of efficient catalytic transformations to quickly convert relatively simple starting materials into more complex valueadded products. Within multi-catalytic processes either multiple catalysts execute single reactions or precise sequences of multiple catalytic reactions occur in a 'one-pot' fashion. Attractively, multi-catalytic protocols not only enable transformations that are inaccessible through classic approaches, but also are able to significantly reduce the time, waste, and cost of the synthetic processes, making organic synthesis more resources efficient. In this Perspective article, we review different strategies in multi-catalysis that bring distinct challenges and opportunities. We divide this overarching field into three main categories: cooperative, domino, and relay catalysis. Each category is described along with representative examples to highlight its features. Special emphasis is dedicated to relay catalysis, which is further discussed in its sub-categories. Lastly, we provide an analysis of systems that incorporate higher levels of complexity and further underscore the potential of multi-catalytic systems.

Enantio‐ and Diastereodivergent Sequential Catalysis Featuring Two Transition‐Metal‐Catalyzed Asymmetric Reactions

“…[7] This process meets the expected benefits of orthogonal one-pot catalysis, which aims to maximize efficiency in synthesis by skipping intermediate purification steps, therefore minimizing waste and saving time. [8] When we initiated this investigation, allyl enol carbonate 1 a was selected as the model substrate in order to control the sequence of events when both catalysts are present at the outset of the reaction. In contrast to allyl b-keto esters, allyl enol carbonates have the added benefit of having the enone functionality masked until it is revealed by the asymmetric allylation step.…”

Enantioselective α-Arylation of Primary Alcohols under Sequential One-Pot Catalysis

“…The development of a multicatalytic system that executes the envisioned sequential transformation required careful balancing of the conditions to ensure compatibility between the catalysts, reagents, and intermediates of the consecutive steps. [21][22][23][24][25] Special attention must be paid to the selection of the catalysts, considering that any cross-reactivity or any ligand scrambling is likely not only to decrease the required activity but also be detrimental for the overall stereoselectivity. 26,27 The Ru-catalyst containing me-bipam, a chiral phosphoramidite ligand developed by Yamamoto and Miyaura, proved previously both highly enantioselective in the arylation of aldehydes 28,29 and compatible with a series of phosphine-Ru complexes, 18 which represent prospective hydrogen-transfer catalysts.…”

Enzymatic strategies for asymmetric synthesis

“…Being able to combine the advantages of the many disciplines in catalysis (metal, organo-, bio, photo-catalysis) in cascade processes 344 will define how chemicals of the 21 st century are made. [345][346][347][348] Several examples are paving the way toward the merging of enzymes with chemical methods in elaborated (cascade) synthesis. [349][350][351][352][353] Finally, the growing importance of (meta)genomics and ultrahigh-throughput screening, such as seen with microfluidic approaches, 354 will raise new challenges.…”