Abstract:Single-electron N-heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of CÀC bonds. Guided by density functional theory and mechanistic analyses, we report the light-driven synthesis of aliphatic and aamino ketones using single-electron NHC operators. Computational and experimental results reveal that the reactivity of the key radical intermediate is substrate-dependent and can be modulated through steric and electronic parameters of the NHC. Catalyst potential is harnessed in … Show more
“…Pinacolato boryl or halogen groups, which are generally reactive to transition-metal catalysis, were compatible under these reaction conditions ( 4ad , 4ag , and 4ah ). Aliphatic carboxylic acid 3i , which would change spin density localization in the ketyl radical state, also gave acylation product 4ai , albeit in low yield …”
Section: Results
and Discussionmentioning
confidence: 99%
“…Aliphatic carboxylic acid 3i, which would change spin density localization in the ketyl radical state, also gave acylation product 4ai, albeit in low yield. 16 Radical Relay-Type Alkylacylation of Alkenes. To enhance the utility of the reaction, we embarked on the development of a three-component reaction based on a radical relay process.…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…There have been significant advancements in N -heterocyclic carbene (NHC) catalysis based on radical–radical coupling via the SET event between reaction substrates. − Specifically, we have described NHC-catalyzed decarboxylative cross-coupling between aldehydes and aliphatic carboxylic acid-derived redox active esters. − The reaction involves SET from the enolate form of the Breslow intermediate derived from an aldehyde and NHC in the presence of a base to form the redox active ester, followed by radical–radical coupling between a persistent ketyl radical and a transient alkyl radical (Figure B, upper). As an alternative approach, SET reduction of an acyl azolium intermediate that can be formed in situ from the NHC catalyst and the carboxylic acid derivative, mainly combined with photoredox catalysis, has emerged as a powerful strategy for the radical–radical coupling recently reported by the Scheidt, − Studer, − and Chi groups (Figure B, bottom). Considering the broad availability of organoboron compounds, their direct use as electron-donating radical sources will enhance the synthetic utility of this catalytic system .…”
Radical–radical
coupling, the selective reaction between
two different radical species, has contributed to the methodology
for connecting bulky units. Light-driven N-heterocyclic
carbene (NHC) organocatalysis is recognized as a state-of-the-art
methodology enabling radical–radical coupling. The catalytic
process involves forming an acyl azolium intermediate from the NHC
catalyst and an acyl donor, followed by single electron reduction
of this key intermediate, which is largely dependent on the photoredox
catalyst. We designed a radical NHC catalysis in which the direct
photoexcitation of a borate to form a high reducing agent facilitated
the single electron reduction event. The borate produces an alkyl
radical for the single electron transfer process to accomplish the
radical–radical coupling. This protocol enables cross-coupling
between alkylborates and acyl imidazoles in addition to radical relay-type
alkylacylations of alkenes with alkylborates and acyl imidazoles,
affording ketones with a broad scope.
“…Pinacolato boryl or halogen groups, which are generally reactive to transition-metal catalysis, were compatible under these reaction conditions ( 4ad , 4ag , and 4ah ). Aliphatic carboxylic acid 3i , which would change spin density localization in the ketyl radical state, also gave acylation product 4ai , albeit in low yield …”
Section: Results
and Discussionmentioning
confidence: 99%
“…Aliphatic carboxylic acid 3i, which would change spin density localization in the ketyl radical state, also gave acylation product 4ai, albeit in low yield. 16 Radical Relay-Type Alkylacylation of Alkenes. To enhance the utility of the reaction, we embarked on the development of a three-component reaction based on a radical relay process.…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…There have been significant advancements in N -heterocyclic carbene (NHC) catalysis based on radical–radical coupling via the SET event between reaction substrates. − Specifically, we have described NHC-catalyzed decarboxylative cross-coupling between aldehydes and aliphatic carboxylic acid-derived redox active esters. − The reaction involves SET from the enolate form of the Breslow intermediate derived from an aldehyde and NHC in the presence of a base to form the redox active ester, followed by radical–radical coupling between a persistent ketyl radical and a transient alkyl radical (Figure B, upper). As an alternative approach, SET reduction of an acyl azolium intermediate that can be formed in situ from the NHC catalyst and the carboxylic acid derivative, mainly combined with photoredox catalysis, has emerged as a powerful strategy for the radical–radical coupling recently reported by the Scheidt, − Studer, − and Chi groups (Figure B, bottom). Considering the broad availability of organoboron compounds, their direct use as electron-donating radical sources will enhance the synthetic utility of this catalytic system .…”
Radical–radical
coupling, the selective reaction between
two different radical species, has contributed to the methodology
for connecting bulky units. Light-driven N-heterocyclic
carbene (NHC) organocatalysis is recognized as a state-of-the-art
methodology enabling radical–radical coupling. The catalytic
process involves forming an acyl azolium intermediate from the NHC
catalyst and an acyl donor, followed by single electron reduction
of this key intermediate, which is largely dependent on the photoredox
catalyst. We designed a radical NHC catalysis in which the direct
photoexcitation of a borate to form a high reducing agent facilitated
the single electron reduction event. The borate produces an alkyl
radical for the single electron transfer process to accomplish the
radical–radical coupling. This protocol enables cross-coupling
between alkylborates and acyl imidazoles in addition to radical relay-type
alkylacylations of alkenes with alkylborates and acyl imidazoles,
affording ketones with a broad scope.
“…1b , bottom). Scheidt 57 , 58 and our group 64 used Hantzsch esters as precursors of the other transient radical intermediates to furnish two-component radical coupling reactions (Fig. 1c ).…”
Section: Introductionmentioning
confidence: 99%
“…bring undesired operations and pose limitations on substrate scopes. In addition, despite the seminal work achieved in NHC and photocatalyst co-catalyzed ketone synthesis 57 – 64 , three-component radical relay coupling that involves various carbon radicals is still limited 58 , 72 . Fig.…”
The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids are directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction is successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.
N‐heterocyclic carbenes (NHCs) have emerged as catalysts for the construction of C−C bonds in the synthesis of substituted ketones under single‐electron processes. Despite these recent reports, there still remains a need to increase the utility and practicality of these reactions by exploring new radical coupling partners. Herein, we report the synthesis of γ‐aryloxyketones via combined NHC/photoredox catalysis. In this reaction, an α‐aryloxymethyl radical is generated via oxidation of an aryloxymethyl potassium trifluoroborate salt, which is then added into styrene derivatives to provide a stabilized benzylic radical. Subsequent radical‐radical coupling reaction with an azolium radical affords the γ‐aryloxy ketone products.
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