Alkynylation of C(O)–H Bonds Enabled by Photoredox‐Mediated Hydrogen‐Atom Transfer

Mukherjee, Satobhisha; Garza‐Sanchez, R. Aleyda; Tlahuext‐Aca, Adrian; Glorius, Frank

doi:10.1002/anie.201708037

Cited by 103 publications

(51 citation statements)

References 69 publications

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“…[1a, 23] Single-electron reduction of the resulting species would provide an azolium radical ion that, when coupled with an alkyl radical, would furnish synthetically valuable ketones (Scheme 1 D). Traditional methods for accessing acyl radicals, which are functionally equivalent to achiral azolium radicals, involve the use of aldehydes, [24] a-keto acids, [25] and others, [26] many of which suffer from significant drawbacks (i.e. toxicity, instability, superstoichiometric additive requirements, etc.).…”

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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“…[2,3] Specifically,C (sp 3 )ÀHf unctionalization involving ah ydrogen-atom transfer (HAT) process driven by photoenergy is attractive due to the mild reaction conditions and high functional-group tolerance. [4] In combination with av isible-light photoredox catalysis, structurallyd istinct HATcatalysts, such as thiols, [5] thiophosphoric acids and imides, [6] quinuclidines, [7] sulfonamides, [8] chloride [9] and bromide [10] ions, aryl carboxylates, [11] and N-hydroxy compounds [12] wered eveloped. The currently-available HAT catalysts have limitations,s uch as:1)limited scope of cleavable CÀHb onds; [13] 2) catalystd ecomposition due to the inherent nucleophilicity [14] and/or reactivity with carbon-carbonm ultiple bonds; [15] and 3) insufficient stability, [16] thus leaving room for improvement.…”

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confidence: 99%

“…The reactionb etween N-Boc pyrrolidine (3a)a nd p-toluenesulfonyl cyanide (TsCN, 4a)i nt he presence of K 2 CO 3 produced cyanation product 5a in 56 %y ield (entry 1). When using previously reported HATc atalysts, such as quinuclidine (2b), [7] benzoic acid (2c), [11] and triisoproplysilylthiol (2d) [5] instead of 2a, 5a was obtained in low yield (entries 2-4). Further optimization of the reaction conditions improved the yield of 5a to 95 %w hen the catalyst loadings of 1 and 2a were reduced to 1a nd 5mol %, respectively,i nd ichloromethane solvent (condition B, entry 5).…”

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confidence: 99%

C(sp³)−H Cyanation Promoted by Visible‐Light Photoredox/Phosphate Hybrid Catalysis

Wakaki

Sakai

Enomoto

et al. 2018

Chemistry A European J

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Inspired by the reaction mechanism of photo-induced DNA cleavage in nature, a C(sp )-H cyanation reaction promoted by visible-light photoredox/phosphate hybrid catalysis was developed. Phosphate radicals, generated by one-electron photooxidation of phosphate salt, functioned as a hydrogen-atom-transfer catalyst to produce nucleophilic carbon radicals from C(sp )-H bonds with a high bond-dissociation energy. The resulting carbon radicals were trapped by a cyano radical source (TsCN) to produce the C-H cyanation products. Due to the high functional-group tolerance and versatility of the cyano group, the reaction will be useful for realizing streamlined building block syntheses and late-stage functionalization of drug-like molecules.

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“…In 2017 Glorius et al reported the synthesis of ynones from aldehydes (Scheme ) . Photoredox‐mediated hydrogen‐atom transfer under blue light irradiation provided access to acyl radicals.…”

Section: C–c Bond: Sp2‐sp Disconnectionmentioning

confidence: 99%

A Retrosynthetic Approach for Photocatalysis

et al. 2020

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Visible‐light‐mediated chemical reactions have become very popular within the last 15 years. Many excellent reviews have summarized reaction principles and recent results in photochemistry and photocatalysis. However, despite their popularity photochemistry and photoredox catalysis are not regular parts of the bachelor and master curriculum of chemistry education. As a consequence, most chemists will use in synthesis planning classic retrosynthetic disconnections and only rarely consider photocatalytic steps. The aim of this article is to be a useful tool for synthetic chemists, that are interested in the synthetic aspects of photocatalysis and looking for a specific retrosynthetic disconnection. Not only are informative schemes provided but also are the availability of the catalysts and reagents as well as the functional group tolerance of the respective method briefly discussed.

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Alkynylation of C(O)–H Bonds Enabled by Photoredox‐Mediated Hydrogen‐Atom Transfer

Cited by 103 publications

References 69 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**

C(sp³)−H Cyanation Promoted by Visible‐Light Photoredox/Phosphate Hybrid Catalysis

A Retrosynthetic Approach for Photocatalysis

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Alkynylation of C(O)–H Bonds Enabled by Photoredox‐Mediated Hydrogen‐Atom Transfer

Cited by 103 publications

References 69 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**

C(sp3)−H Cyanation Promoted by Visible‐Light Photoredox/Phosphate Hybrid Catalysis

A Retrosynthetic Approach for Photocatalysis

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C(sp³)−H Cyanation Promoted by Visible‐Light Photoredox/Phosphate Hybrid Catalysis