Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a 'pre-fuel'. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be reprogrammed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in lifelike non-equilibrium systems. File list (4) download file view on ChemRxiv REV_SachCHO_20191221_Chemrxiv.pdf (1.38 MiB) download file view on ChemRxiv REV_SI_SachCHO_20191221_GF_v2.pdf (1.37 MiB) download file view on ChemRxiv Video1_gel-sol-gel_vial.mp4 (109.69 MiB) download file view on ChemRxiv Video2_microscopy.mp4 (62.71 MiB)

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.

Secondary benzylic alcohols (SBAs) and diarylmethanols (DAMs) are common structural motifs of biologically active and medicinally relevant compounds. Here we report their enantioselective synthesis by -arylation of primary aliphatic and benzylic alcohols under sequential catalysis integrating a Ru-catalyzed hydrogen-transfer oxidation and a Ru-catalyzed nucleophilic addition. The method is applicable to various alcohols and aryl nucleophiles tolerating a range of functional groups, including secondary alcohols, ketones, alkenes, esters, NH-amides, tertiary amines, aryl halides, and heterocycles.Secondary benzylic alcohols (SBAs) and diarylmethanols (DA Ms) constitute valuable synthetic intermediates and prevalent structural motifs of numerous natural products and bioactive compounds. 1,2 Therefore, protocols for their stereoselective synthesis from various accessible starting materials have attracted much attention over the years. Common approaches include potent asymmetric (transfer) hydrogenation of ketones 1,3,4 or 1,2-addition of aryl nucleophiles to aldehydes, 5,6 particularly useful for fine-chemical synthesis when such starting materials are available and do not require additional synthetic steps.Because aliphatic alcohols represent a class of abundant starting materials, increasing attention has been devoted to developing methods for their valorization through selective C−H bond functionalization. [7][8][9] In the context of SBAs, an elegant strategy for the enantioselective alkylation of -C−H bonds of primary benzylic alcohols with unsaturated hydrocarbons (e.g., dienes, enynes) was devised by Krische and co-workers (Scheme 1a). 10,11 The methods of the arylation of -C−H bonds of aliphatic alcohols in the Minisci-type reactions were also established. [12][13][14][15][16][17] (Scheme 1b). Unfortunately, these methods lead to racemic products, leaving the enantioselective -C−H arylation of alcohols unexplored.We have recently reported an enantioselective synthesis of SBAs from unsaturated alcohols and aryl boronic acids under sequential catalysis (Scheme 1c). 18 The one-pot sequence of an Ir-catalyzed isomerization of the starting material and a Ru-catalyzed nucleophilic addition of an aryl boronic acid to the aldehyde intermediate provided a convenient synthetic method with a broad scope and functional group tolerance.

One-pot multi-step procedures bear the potential to rapidly build up molecular complexity while avoiding the wasteful and costly isolations and purifications of consecutive intermediates. Here we report multi-catalytic protocols that convert alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivities under sequential catalysis that integrates alkene cross-metathesis, isomerization, and nucleophilic addition. Because each transformation of the sequence is executed by an independent catalyst, without any catalytic cross-reactivity, allylic alcohols bearing a prochiral double bond can be converted to any stereoisomer of the product with high stereoselectivity (>98:2 er and >20:1 dr). Overall, with the aid of up to four catalysts operating in a single vessel, the protocols directly convert simple starting materials into a range of value-added products with high stereocontrol and excellent material efficiency, demonstrating both the efficacy and the advantages of the one-pot synthesis employing multiple transition-metal catalysts.

Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a ‘pre-fuel’. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be re-programmed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in life-like non-equilibrium systems.

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Water soluble amphiphilic urea-substituted β-cyclodextrins were synthesized and applied as amino acid receptors.

Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a ‘pre-fuel’. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be re-programmed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in life-like non-equilibrium systems.