Nickel‐Catalyzed Enantioselective Decarboxylative Acylation: Rapid, Modular Access to α‐Amino Ketones**

Gao, Yang; Baran, Phil S.

doi:10.1002/anie.202315203

Cited by 10 publications

(4 citation statements)

References 70 publications

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“…Some NHP esters exhibit enhanced reactivity compared with the corresponding benzyl chlorides, and the method allows access to compounds that were challenging to prepare via previous coupling methods. Preliminary findings suggested the adaptability of these conditions for α-alkoxy NHP esters ( 23e ) and other difficult substrates, thereby offering flexibility in choosing between NHP esters and benzylic chlorides on the basis of practical considerations like starting material availability …”

Section: Synthetic Methods Developmentmentioning

confidence: 99%

Section: Synthetic Methods Developmentmentioning

confidence: 99%

“…Preliminary findings suggested the adaptability of these conditions for α-alkoxy NHP esters (23e) and other difficult substrates, thereby offering flexibility in choosing between NHP esters and benzylic chlorides on the basis of practical considerations like starting material availability. 44 In 2022, a collaboration between Merck scientists and our group prompted us to develop a Ni/photoredox dual catalysis system between racemic N-benzylic trifluoroborates (BF 3 K) and heteroaryl bromides to access N-benzylic heterocycles, 45 a common structural motif found in pharmaceuticals (Figure 8). While this approach is not a reductive coupling, it provides access to enantioenriched products related to the diarylalkanes shown in Figure 7.…”

Section: Other Benzylic Radical Precursorsmentioning

confidence: 99%

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Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis

Chen,

Reisman

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: After decades of palladium dominating the realm of transition-metal-catalyzed cross-coupling, recent years have witnessed exciting advances in the development of new nickel-catalyzed cross-coupling reactions to form C(sp 3 ) centers. Nickel possesses distinct properties compared with palladium, such as facile single-electron transfer to C(sp 3 ) electrophiles and rapid C−C reductive elimination from Ni III . These properties, among others, make nickel particularly well-suited for reductive cross-coupling (RCC) in which two electrophiles are coupled and an exogenous reductant is used to turn over the metal catalyst. Ni-catalyzed RCCs use readily available and stable electrophiles as starting materials and exhibit good functional group tolerance, which makes them appealing for applications in the synthesis of complex molecules. Building upon the foundational work in Ni-catalyzed RCCs by the groups of Kumada, Durandetti, Weix, and others, as well as the advancements in Ni-catalyzed enantioselective redox-neutral cross-couplings led by Fu and co-workers, we initiated a program to explore the feasibility of developing highly enantioselective Ni-catalyzed RCCs. Our research has also been driven by a keen interest in unraveling the factors contributing to enantioinduction and electrophile activation as we seek new avenues for advancing our understanding and further developing these reactions.In the first part of this Account, we organize our reported methods on the basis of the identity of the C(sp 3 ) electrophiles, including benzylic chlorides, N-hydroxyphthalimide (NHP) esters, and α-chloro esters and nitriles. We highlight how the selection of specific chiral ligands plays a pivotal role in achieving high cross-selectivity and enantioselectivity. In addition, we show that reduction can be accomplished not only with heterogeneous reductants, such as Mn 0 , but also with the soluble organic reductant tetrakis(dimethylamino)ethylene (TDAE), as well as electrochemically. The use of homogeneous reductants, such as TDAE, is well suited for studying the mechanism of the transformation. Although this Account primarily focuses on RCCs, we also highlight our work using trifluoroborate (BF 3 K) salts as radical precursors for enantioselective dual-Ni/photoredox systems. At the end of this Account, we summarize the relevant mechanistic studies of two closely related asymmetric reductive alkenylation reactions developed in our laboratory and provide a context between our work and related mechanistic studies by others. We discuss how the ligand properties influence the rates and mechanisms of electrophile activation and how understanding the mode of C(sp 3 ) radical generation can be used to optimize the yield of an RCC. Our research endeavors to offer insights on the intricate mechanisms at play in asymmetric Ni-catalyzed RCCs with the goal of using the rate of electrophile activation to improve the substrate scope of enantioselective RCCs. We anticipate that the insights we shar...

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Section: Synthetic Methods Developmentmentioning

confidence: 99%

Section: Synthetic Methods Developmentmentioning

confidence: 99%

Section: Other Benzylic Radical Precursorsmentioning

confidence: 99%

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Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis

Chen,

Reisman

2024

Acc. Chem. Res.

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“…Unactivated alkenes such as internal β,γ-unsaturated amides also participate in catalytic hydroacylation with high regio- and enantioselectivities, demonstrating the general applicability of the catalyst to encompass diverse internal alkenes. While enantioenriched α-amino ketones and 1,4-dicarbonyl compounds are versatile building blocks, catalytic methods for the asymmetric synthesis of such compounds are relatively rare. , This hydroacylation protocol provides complementary access to these valuable structure motifs. Computational studies reveal that hydrogen bonding of the JoSPO ligand to the carbonyl group in the acyl Rh(III) hydride species facilitates C(acyl)–H cleavage and helps to suppress the undesired decarbonylation pathway.…”

Section: Introductionmentioning

confidence: 99%

Amide-Directed, Rhodium-Catalyzed Regio- and Enantioselective Hydroacylation of Internal Alkenes with Unfunctionalized Aldehydes

Sun,

Gao,

Sun

et al. 2023

J. Am. Chem. Soc.

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Despite the current progress achieved in asymmetric hydroacylations, highly enantioselective catalytic addition of unfunctionalized aldehydes to internal alkenes remains an unsolved challenge. Here, using a coordination-assisted strategy, we developed a rhodium-catalyzed regio-and enantioselective addition of unfunctionalized aldehydes to internal alkenes such as enamides and β,γ-unsaturated amides. Valuable α-amino ketones and 1,4dicarbonyl compounds were directly obtained with high enantioselectivity from readily available materials.

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Electrochemical Decarboxylation Coupling Reactions

Liu,

Li,

Guo

et al. 2024

Chemistry A European J

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Carboxylic acids are attractive synthetic feedstocks with stable, non‐toxic, and inexpensive properties that can be easily obtained from natural sources or through synthesis. Carboxylic acids have long been considered environmentally friendly coupling agents in various organic transformations. In recent years, electrochemically mediated decarboxylation reactions of decarboxylic acids and their derivatives (NHPI) have emerged as effective new methods for constructing carbon‐carbon or carbon‐heterocarbon chemical bonds. Compared with transition metal and photochemistry‐mediated catalytic reactions, which do not require the addition of oxidants and strong bases, electrochemically‐mediated decarboxylative transformations are considered a sustainable strategy. In addition, various functional groups tolerate the electrochemical decarboxylation conversion strategy well. Here, we summarize the recent electrochemical decarboxylation reactions to better elucidate the advantages of electrochemical decarboxylation reactions.

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Nickel‐Catalyzed Enantioselective Decarboxylative Acylation: Rapid, Modular Access to α‐Amino Ketones**

Cited by 10 publications

References 70 publications

Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis

Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis

Amide-Directed, Rhodium-Catalyzed Regio- and Enantioselective Hydroacylation of Internal Alkenes with Unfunctionalized Aldehydes

Electrochemical Decarboxylation Coupling Reactions

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Nickel‐Catalyzed Enantioselective Decarboxylative Acylation: Rapid, Modular Access to α‐Amino Ketones**

Cited by 10 publications

References 70 publications

Enantioselective C(sp2)–C(sp3) Bond Construction by Ni Catalysis

Enantioselective C(sp2)–C(sp3) Bond Construction by Ni Catalysis

Amide-Directed, Rhodium-Catalyzed Regio- and Enantioselective Hydroacylation of Internal Alkenes with Unfunctionalized Aldehydes

Electrochemical Decarboxylation Coupling Reactions

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Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis

Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis