High Throughput Strategies for the Discovery and Optimization of Catalytic Reactions

Isbrandt, Eric S.; Sullivan, Ryan J.; Newman, Stephen G.

doi:10.1002/anie.201812534

Cited by 131 publications

(103 citation statements)

References 140 publications

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“…Our initial search for the desired reactivity was guided by semi-high-throughput experimentation (HTE), which allowed numerous reaction components to be screened in parallel. [32] Semi-HTE enabled facile and rapid identification of the most optimal alkyl radical precursor for this transformation. While limited reactivity was achieved with alkyl silanes, [33] silicates, [34] and potassium trifluoroborate salts (R-BF 3 K), [35] significant conversion was observed using Hantzsch esters [36] as the alkyl radical source.…”

Section: N-heterocyclic Carbenes (Nhcs) Have Emerged As Uniquementioning

confidence: 99%

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids**

et al. 2020

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As a key element in the construction of complex organic scaffolds, the formation of C À C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various CÀC bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical-radical coupling was made possible merging Nheterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the latestage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies. N-heterocyclic carbenes (NHCs) have emerged as uniqueLewis basic catalysts that harness umpolung (polarity reversal) reactivity to mediate a wide range of organic transformations. [1] The majority of NHC-catalyzed processes are initiated by carbene addition into a carbonyl. Subsequent proton transfer affords the Breslow intermediate, [2] a species that is nucleophilic at a typically electrophilic carbonyl carbon center. While the utility of two-electron NHC reactivity has continued to expand since the fields inception, the scope with respect to NHC-derived operators is limited by their inability to engage sp 3 electrophiles, thus highlighting the potential opportunity for single-electron NHC operators.Early work from our group showcased a mild oxidation of allylic alcohols [2b] and aldehydes [3] to esters using an NHC and MnO 2 (Scheme 1 A). Oxidation of the Breslow intermediate with stoichiometric MnO 2 was employed to access an acyl azolium intermediate, and subsequent displacement by an alcohol afforded the desired C À O bond. Shortly thereafter, Studer and co-workers developed an NHC-catalyzed oxidation of aldehydes to esters mediated by 2,2,6,6-tetramethyl-1

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Section: N-heterocyclic Carbenes (Nhcs) Have Emerged As Uniquementioning

confidence: 99%

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids**

et al. 2020

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“…Microdroplets provide excellent platforms for microreactions and have elicited enormous research interest for their potential application in biological assays, [1][2][3][4] combinatorial analysis, [5][6][7][8][9][10] and drug discovery, [11,12] for which it is crucial to separate microdroplets and deposit them into desired locations with as pecific arrangement and morphology.S of ar, various methods have been developed and employed to distribute microdroplets,s uch as inkjet printing,d ispensing, discontinuous dewetting, and microfluidics. [13][14][15][16] Forexample, biosample suspensions were separated into microdroplet arrays and used for incubation and screening, [17] and microdroplets of ac olloidal nanoparticle solution were dispensed and assembled for fluorescence-based metal-ion recognition.…”

Section: Introductionmentioning

confidence: 99%

Droplet Precise Self‐Splitting on Patterned Adhesive Surfaces for Simultaneous Multidetection

Fang

Zhao

et al. 2020

Angewandte Chemie

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Precise separation and localization of microdroplets are fundamental for various fields, such as high‐throughput screening, combinatorial chemistry, and the recognition of complex analytes. We have developed a droplet self‐splitting strategy to divide an impacting droplet into predictable microdroplets and deposit them at preset spots for simultaneous multidetection. No matter exchange was observed between these microdroplets, so they could be manipulated independently. Droplet self‐splitting was attributed to anisotropic liquid recoiling on the patterned adhesive surface, as influenced by the droplet Weber number and the width of the low‐adhesive stripe. A quantitative criterion was also developed to judge the droplet self‐splitting capability. The precise separation and distribution of microdroplets enabled simultaneous arrayed reactions and multiple analyte detection using one droplet of sample.

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“…The ever increasing interest and value of flow chemistry technologies (Bogdan and Dombrowski, 2019) has led to highly integrated systems as well [ Figure 1E MIT's Pharmacy on Demand module (Adamo et al, 2016), Figure 1F MIT's Reconfigurable Self-Optimizing Reactor (Bedard et al, 2018)]. High throughput reaction screening platforms have recently seen a resurgence of interest (Buitrago Santanilla et al, 2015;Perera et al, 2018;Isbrandt et al, 2019). But it is interesting to note how often one can find footnotes to highly automated and productive platforms being fed by substrates that have been synthesized manually.…”

Section: Introductionmentioning

confidence: 99%

A Perspective on Innovating the Chemistry Lab Bench

et al. 2020

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Innovating on the design and function of the chemical bench remains a quintessential challenge of the ages. It requires a deep understanding of the important role chemistry plays in scientific discovery as well a first principles approach to addressing the gaps in how work gets done at the bench. This perspective examines how one might explore designing and creating a sustainable new standard for advancing automated chemistry bench itself. We propose how this might be done by leveraging recent advances in laboratory automation whereby integrating the latest synthetic, analytical and information technologies, and AI/ML algorithms within a standardized framework, maximizes the value of the data generated and the broader utility of such systems. Although the context of this perspective focuses on the design of advancing molecule of potential therapeutic value, it would not be a stretch to contemplate how such systems could be applied to other applied disciplines like advanced materials, foodstuffs, or agricultural product development.

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High Throughput Strategies for the Discovery and Optimization of Catalytic Reactions

Cited by 131 publications

References 140 publications

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids**

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids**

Droplet Precise Self‐Splitting on Patterned Adhesive Surfaces for Simultaneous Multidetection

A Perspective on Innovating the Chemistry Lab Bench

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