Synthesis of α-Heteroaryl Propionic Esters by Palladium-Catalyzed α-Heteroarylation of Silyl Ketene Acetals

Li, Bowen; Luo, Bangke; Blakemore, Caroline A.; Smith, Aaron; Widlicka, Daniel W.; Berritt, Simon; Tang, Wenjun

doi:10.1021/acs.orglett.1c02257

Cited by 6 publications

(3 citation statements)

References 27 publications

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“…We reported a practical synthesis of α-heteroaryl propionic esters via efficient palladium-catalyzed α-heteroarylation of silyl ketene acetals in high yields (Scheme 15A). 37 The implementation of bulky BOPPO ligands was critical to achieving the transformation. By taking advantage of the hemilabile BOPPO catalytic system, a regioselective 2-alkylation of indoles with α-bromo esters was also achieved in good yields (Scheme 15B).…”

Section: Heck-type Reactionsmentioning

confidence: 99%

“… An acceptable yield (73%) was obtained, although a stoichiometric palladium species was employed. We reported a practical synthesis of α-heteroaryl propionic esters via efficient palladium-catalyzed α-heteroarylation of silyl ketene acetals in high yields (Scheme A) . The implementation of bulky BOPPO ligands was critical to achieving the transformation.…”

Section: Oxaphosphole-based Ligands For Cross-coupling Reactionsmentioning

confidence: 99%

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Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

Cao,

He,

Tang

2024

Org. Process Res. Dev.

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P-Chiral phosphorus ligands received little attention in organic chemistry until Knowles made his landmark contribution in asymmetric hydrogenation by developing the P-chiral ligands CAMP and DIPAMP. The development of P-chiral phosphorus ligands accelerated in the end of the last century with the advent of some highly efficient and renowned ligands for asymmetric hydrogenation, including BisP*, TangPhos, QuinoxP*, DuanPhos, et al. However, most reported ligands were airsensitive, difficult to make, or lacked structural modularity, hampering their availability and applicability. The development of sterically and electronically tunable P-chiral phosphorus ligands is particularly desirable. Over the past decade, a family of sterically hindered, electron-rich, structurally tunable, and air-stable P-chiral dihydrobenzooxaphosphole ligands emerged that proved to be efficient and versatile for various asymmetric transformations. The last 5 years witnessed an increasing number of studies related to these ligands with the discovery of their unprecedented catalytic properties in various transformations. This review highlights the unique properties of P-chiral dihydrobenzooxaphosphole ligands in catalysis and their applications in the synthesis of natural products and therapeutic agents.

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Section: Heck-type Reactionsmentioning

confidence: 99%

Section: Oxaphosphole-based Ligands For Cross-coupling Reactionsmentioning

confidence: 99%

Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

Cao,

He,

Tang

2024

Org. Process Res. Dev.

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“…Pyridines are the most prevalent heterocyclic structures found in pharmaceutical products, among which pyridylacetic acid derivatives find use both as subunits of drugs and drug candidates and also as intermediates for their synthesis (Figure ). Synthetic routes to substituted pyridylacetate derivatives (and their benzo-fused (iso)quinoline analogues) frequently start from halopyridines under conditions of palladium-catalyzed cross-coupling with lithium enolates, , silyl enol ethers, or Reformatsky reagents . Alternatively, metal-catalyzed , coupling or direct S N Ar reactions of halopyridines and (iso)quinolines can be carried out with activated methylene compounds such as malonates, ,, ketoesters, cyanoacetate, , or Meldrum’s/barbituric acids, followed by hydrolysis/decarboxylation or deacylation.…”

Section: Introductionmentioning

confidence: 99%

Three-Component Synthesis of Pyridylacetic Acid Derivatives by Arylation/Decarboxylative Substitution of Meldrum’s Acids

Johnson

Marsden

2022

J. Org. Chem.

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Heck Reaction of N‐Heteroaryl Halides for the Concise Synthesis of Chiral α‐Heteroaryl‐substituted Heterocycles

Luo

Yang

et al. 2022

Angewandte Chemie

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The Heck reaction between N-heteroaryl halides and heterocyclic alkenes provides a convenient approach to biologically relevant α-heteroaryl functionalized heterocycles, yet reactions of this type have been challenging due to strong N-heteroaryl coordination to palladium metal, which causes catalyst poisoning. In this report, an efficient palladium-catalyzed Heck reaction between N-heteroaryl halides and heterocyclic olefins is established, leading to a variety of α-heteroaryl substituted heterocycles. The method features an unprecedented broad substrate scope and excellent functional group compatibility. The employment of a sterically bulky P, P=O ligand containing an anthryl moiety is crucial for this transformation due to the coordinative unsaturation facilitated by its steric bulkiness. The asymmetric variant of the Heck reaction is achieved with (S)-DTBM-SEGPHOS via a cationic palladium pathway, which has enabled an efficient asymmetric synthesis of (S)-nicotine and its analogues.

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Synthesis of α-Heteroaryl Propionic Esters by Palladium-Catalyzed α-Heteroarylation of Silyl Ketene Acetals

Cited by 6 publications

References 27 publications

Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

Three-Component Synthesis of Pyridylacetic Acid Derivatives by Arylation/Decarboxylative Substitution of Meldrum’s Acids

Heck Reaction of N‐Heteroaryl Halides for the Concise Synthesis of Chiral α‐Heteroaryl‐substituted Heterocycles

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