C–H Functionalization of Heteroarenes Using Unactivated Alkyl Halides through Visible-Light Photoredox Catalysis under Basic Conditions

Bissonnette, Noah B.; Boyd, Michael J.; May, Gregory D.; Giroux, Simon; Nuhant, Philippe

doi:10.1021/acs.joc.8b01589

Cited by 39 publications

(30 citation statements)

References 40 publications

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“…Nuhant and co-workers recently demonstrated the Minisci-type reaction of radical fragments derived from alkyl iodides through iridium photoredox catalysis (Scheme 57). [135] Ther eaction proceeds using 2,2,6,6-tetramethylpiperidine (HTMP) as ab ase and sacrificial cycle-initiating reductant. Thescope is broad with respect to heteroarenes,and avariety of primary,secondary and tertiary fragments can be coupled.…”

Section: Angewandte Chemiementioning

confidence: 99%

Recent Advances in Minisci‐Type Reactions

2019

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Reactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. First developed into a useful synthetic tool in the late 1960s by Minisci, this reaction type has been in constant use over the last half century by chemists seeking to functionalize heterocycles in a rapid and direct manner, avoiding the need for de novo heterocycle synthesis. Whilst the originally developed protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder and more benign conditions. The recent surge of interest in new transformations based on free radical reactivity has meant that numerous choices are now available to a synthetic chemist looking to utilize a Minisci‐type reaction. Radical‐generation methods based on photoredox catalysis and electrochemistry have joined approaches which utilize thermal cleavage or the in situ generation of reactive radical precursors. This review will cover the remarkably large body of literature that has appeared on this topic over the last decade in an attempt to provide guidance to the synthetic chemist, as well as a perspective on both the challenges that have been overcome and those that still remain. As well as the logical classification of advances based on the nature of the radical precursor, with which most advances have been concerned, recent advances in control of various selectivity aspects associated with Minisci‐type reactions will also be discussed.

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Section: Angewandte Chemiementioning

confidence: 99%

Recent Advances in Minisci‐Type Reactions

2019

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“…As an interesting note, the in situ generation of alkyl halides by treatment with an iodo‐Ghosez reagent also allowed the use of alcohols as alkylating agents. Additional processes based on iridium photoredox catalysis have been reported recently for the direct alkylation of nitrogen‐containing heteroarenes with unactivated primary, secondary, and tertiary alkyl iodides ,…”

Section: Alkylation Of Heteroarenesmentioning

confidence: 99%

“…Since alkyl radicals are remarkably efficient intermediates for the alkylation of electron‐rich arenes, photoredox catalysis represents a logical and interesting possibility in such processes. They can indeed be readily generated from unactivated alkyl halides in the presence of a photoredox catalyst and light, as illustrated by the direct alkylation of 1‐methylindole‐3‐carboxaldehyde with various alkyl iodides under iridium‐catalyzed photoredox conditions, as well as by the palladium‐catalyzed direct alkylation of 1‐benzothiophene‐3‐carbaldehyde (and some other heterocycles) with secondary and tertiary alkyl bromides under irradiation with a blue LED…”

Section: Alkylation Of Heteroarenesmentioning

confidence: 99%

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

Evano

Theunissen

2019

Angew Chem Int Ed

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Alkylated arenes are ubiquitous molecules and building blocks commonly utilized in most areas of science where there is a need for small organic molecules. Despite its apparent simplicity, the regioselective alkylation of arenes is still a challenging transformation in a lot of cases. Classical methods for the introduction of alkyl groups on arenes, which include the venerable Friedel-Crafts reaction, radical additions, metallation or pre-functionalization of the arene, as well as alternatives such as the directed alkylation of C-H bonds, still suffer from severe limitations in terms of scope, efficiency and selectivity. This can be addressed by exploiting the innate reactivity of some (hetero)arenes, in which electronic and steric properties, governed (or not) by the presence of one (or multiple) heteroatom(s) ensure high levels of regioselectivity. These innate alkylations of C-H bonds in (hetero)arenes will be overviewed, in a comprehensive manner, in this review article.

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“…[3] In the past decade, with the development of photoredox catalysis, light-induced photoredox Minisci-type alkylation has been intensively explored. Hence, a range of efficient radical precursors were uncovered including alcohols, [4] ethers, [5] alkyl halides, [6] boronic acids, [7] carboxylic acids, [8] and redox active esters (RAEs), [9] among others (Figure 1, a-f). [10] Very recently, Minisci-type reaction with alkanes under oxidative visible-light photocatalysis was explored by Chen, Lei, and Jin et al [11] In spite of these utilities, some limitations in Minisci-type reactions still remain.…”

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confidence: 99%

LiBr‐Promoted Photoredox Minisci‐Type Alkylations of Quinolines with Ethers

Wang

Han

et al. 2019

Adv Synth Catal

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A visible-light-mediated photoredox Minisci-type alkylation with ethers as the alkylating reagent is reported. User-friendly LiBr has been found to be the key promoter for this radical coupling. The reaction exhibits broad functional group tolerance for both C2 and C4 couplings/ alkylations of quinolines. Mechanistic studies suggest that the bromide additive could not only dramatically enhance the reaction but also alter the reaction mechanism probably over a reductive catalytic cycle.

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C–H Functionalization of Heteroarenes Using Unactivated Alkyl Halides through Visible-Light Photoredox Catalysis under Basic Conditions

Cited by 39 publications

References 40 publications

Recent Advances in Minisci‐Type Reactions

Recent Advances in Minisci‐Type Reactions

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

LiBr‐Promoted Photoredox Minisci‐Type Alkylations of Quinolines with Ethers

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