Photons or Electrons? A Critical Comparison of Electrochemistry and Photoredox Catalysis for Organic Synthesis

Chemical Reviews, Год журнала: 2021, Номер 122(2), С. 2487 - 2649

Опубликована: Ноя. 9, 2021

Redox processes are at the heart of synthetic methods that rely on either electrochemistry or photoredox catalysis, but how do and catalysis compare? Both approaches provide access to high energy intermediates (e.g., radicals) enable bond formations not constrained by rules ionic 2 electron (e) mechanisms. Instead, they 1e mechanisms capable bypassing electronic steric limitations protecting group requirements, thus enabling chemists disconnect molecules in new different ways. However, while providing similar intermediates, differ several physical chemistry principles. Understanding those differences can be key designing transformations forging disconnections. This review aims highlight these similarities between comparing their underlying principles describing impact electrochemical photochemical methods.

Язык: Английский

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The Development of Multidimensional Analysis Tools for Asymmetric Catalysis and Beyond

Accounts of Chemical Research, Год журнала: 2016, Номер 49(6), С. 1292 - 1301

Опубликована: Май 24, 2016

ConspectusIn most modern organic chemistry reports, including many of ours, reaction optimization schemes are typically presented to showcase how conditions have been tailored augment the reaction's yield and selectivity. In asymmetric catalysis, this often involves evaluation catalyst, solvent, reagent, and, sometimes, substrate features. Such an article will then detail process's scope, which mainly focuses on its successes briefly outlines "limitations". These limitations or poorer-performing substrates occasionally result obvious, significant changes structure (e.g., a Lewis basic group binds catalyst), but frequently, satisfying explanation for inferior performance is not clear. This one several reasons such results reported. apparent outliers also commonplace in catalyst structure, although information placed Supporting Information.These practices unfortunate because that appear at first glance be peculiar poor considerably more interesting than ones follow obvious intuitive trends. other words, all data from campaign contain relevant about under study, "outliers" may revealing.Realizing power as entry point entirely new development unusual. Nevertheless, concept no should wasted when considering underlying phenomena controlling observations given heart strategy we describe Account. The idea can concurrently optimize expose structural features control outcomes would represent transformative addition arsenal ultimately, de novo design.Herein outline recently initiated program our lab unites with mechanistic interrogation by correlating outputs electrochemical potential enantio-, site, chemoselectivity) descriptors molecules involved. ever-evolving inspiration rooted classical linear free energy relationships. encouraged us ask questions parameters themselves, suggest interactions source observed effects, particular applicability, identify sophisticated physical descriptors. Throughout program, integrated techniques disparate fields, synthetic methodology development, investigations, statistics, computational chemistry, science. implementation these strategies described, resulting tools illustrated wide range case studies, include sets simultaneous multifaceted substrate, structures. tactic constitutes approach wherein hypotheses regarding processes developed probed.

Язык: Английский

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Practical High-Throughput Experimentation for Chemists

ACS Medicinal Chemistry Letters, Год журнала: 2017, Номер 8(6), С. 601 - 607

Опубликована: Май 17, 2017

Large arrays of hypothesis-driven, rationally designed experiments are powerful tools for solving complex chemical problems. Conceptual and practical aspects high-throughput experimentation discussed. A case study in the application to a key synthetic step drug discovery program subsequent optimization first large scale synthesis candidate is exemplified.

Язык: Английский

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The Evolution of Chemical High-Throughput Experimentation To Address Challenging Problems in Pharmaceutical Synthesis

Accounts of Chemical Research, Год журнала: 2017, Номер 50(12), С. 2976 - 2985

Опубликована: Ноя. 27, 2017

ConspectusThe structural complexity of pharmaceuticals presents a significant challenge to modern catalysis. Many published methods that work well on simple substrates often fail when attempts are made apply them complex drug intermediates. The use high-throughput experimentation (HTE) techniques offers means overcome this fundamental by facilitating the rational exploration large arrays catalysts and reaction conditions in time- material-efficient manner. Initial forays into HTE our laboratories for solving chemistry problems centered around screening chiral precious-metal homogeneous asymmetric hydrogenation. success these early efforts developing efficient catalytic steps late-stage development programs motivated desire increase scope approach encompass other high-value chemistries. Doing so, however, required advances reactor workflow design automation enable effective assembly agitation heterogeneous mixtures retention volatile solvents under wide range temperatures. Associated innovations analytical greatly increased efficiency reliability methods. These evolved have been utilized extensively develop highly innovative catalysis solutions most challenging large-scale pharmaceutical synthesis. Starting with Pd- Cu-catalyzed cross-coupling chemistry, subsequent expanded valuable synthetic transformations such as phase-transfer catalysis, photoredox C–H functionalization. As experience confidence matured, we envisioned their application beyond process address needs medicinal chemists. Here problem generality is felt acutely, approaches should prove broadly enabling. However, quantities both time starting materials available troubleshooting space generally severely limited. Adapting led us invest smaller predefined transformation-specific “kits” push boundaries miniaturization screening, culminating “nanoscale” carried out 1536-well plates. Grappling also inspired cheminformatics-driven Chemistry Informer Libraries. next-generation promise empower chemists run orders magnitude more experiments “big data” informatics troubleshooting. With advances, poised revolutionize how across industry academia discover new methods, tools broad utility, practical significance.

Язык: Английский

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Photocatalysis in the Life Science Industry

Chemical Reviews, Год журнала: 2021, Номер 122(2), С. 2907 - 2980

Опубликована: Сен. 24, 2021

In the pursuit of new pharmaceuticals and agrochemicals, chemists in life science industry require access to mild robust synthetic methodologies systematically modify chemical structures, explore novel space, enable efficient synthesis. this context, photocatalysis has emerged as a powerful technology for synthesis complex often highly functionalized molecules. This Review aims summarize published contributions field from industry, including research industrial-academic partnerships. An overview developed strategic applications synthesis, peptide functionalization, isotope labeling, both DNA-encoded traditional library is provided, along with summary state-of-the-art photoreactor effective upscaling photocatalytic reactions.

Язык: Английский

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