A5077024906- Catalytic C–H Functionalization Methods
- Catalytic Cross-Coupling Reactions
- Synthesis and Catalytic Reactions
- Cyclopropane Reaction Mechanisms
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Asymmetric Hydrogenation and Catalysis
- Chemical Synthesis and Analysis
- Advanced Synthetic Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Radical Photochemical Reactions
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
Harvard University
2024
Scripps Research Institute
2015-2020
Peking University
2013-2015
Beijing National Laboratory for Molecular Sciences
2013
Chinese Academy of Sciences
2013
State Key Laboratory of Organometallic Chemistry
2013
2-Carbomethoxynorbornene is identified as a more effective transient mediator to promote Pd(II)-catalyzed meta-C(sp2)–H alkylation of amides with various alkyl iodides well arylation previously incompatible aryl iodides. The use tailor-made quinoline ligand also crucial for this reaction proceed.
Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class ligands that promote meta-C-H arylation anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables wide substrate coupling partner scope. Meta-C-H with aryl iodides partners is also realized for first time ligand. The utility transformation drug discovery showcased by...
The enzymatic β-C-H hydroxylation of the feedstock chemical isobutyric acid has enabled asymmetric synthesis a wide variety polyketides. analogous transition metal-catalyzed enantioselective functionalization acid-derived substrates should provide versatile method for constructing useful building blocks with enantioenriched α-chiral centers from this abundant C-4 skeleton. However, desymmetrization ubiquitous isopropyl moieties by organometallic catalysts remained an unanswered challenge....
Using a modified norbornene (methyl bicyclo[2.2.1]hept-2-ene-2-carboxylate) as transient mediator, meta-C-H amination and alkynylation of aniline phenol substrates have been developed for the first time. Both identification monoprotected 3-amino-2-hydroxypyridine/pyridone-type ligand use mediator are crucial realization these two unprecedented transformations. A variety compatible with both alkynylation. Amination heterocyclic including indole, indoline, indazole afford desired products in...
A monoprotected aminoethyl amine chiral ligand based on an ethylenediamine backbone was developed to achieve Pd-catalyzed enantioselective C(sp3)–H arylation of cyclopropanecarboxylic and 2-aminoisobutyric acids without using exogenous directing groups. This new catalyst affords disconnection for preparing diverse carboxylic from simple starting materials that are complementary the various ring forming approaches.
Abstract Pd II ‐catalyzed enantioselective C(sp 3 )−H cross‐coupling of free carboxylic acids with organoborons has been realized using either mono‐protected amino acid (MPAA) ligands or aminoethyl amine (MPAAM) ligands. A diverse range aryl‐ and vinyl‐boron reagents can be used as coupling partners to provide chiral acids. This reaction provides an alternative approach the synthesis cyclopropanecarboxylic cyclobutanecarboxylic containing α‐chiral tertiary quaternary stereocenters. The...
Palladium-catalyzed primary and secondary sp3 C–H bond arylation is reported. The method using diarylhyperiodonium salts as reagents shows good functional group tolerance proceeds under mild reaction conditions. KIE experiments show that the activation rate-determining step.
A novel rhodium-catalyzed C–C bond formation was developed to construct biaryls through unreactive aryl C–S cleavage of thioethers with boroxines. This protocol provided a supplemental method traditional Suzuki–Miyaura coupling.
Chiral mono-
We report the development of Pd(II)-catalyzed C(sp3)–H arylation Weinreb amides. Both inductive effect and potential bidentate coordination mode amides pose a unique challenge for this reaction development. A pyridinesulfonic acid ligand is designed to accommodate weak, neutral-coordinating property by preserving cationic character Pd center through zwitterionic assembly Pd/ligand complexes. Density functional theory (DFT) studies C–H cleavage step indicate that superior reactivity...
DNA-compatible C(sp<sup>3</sup>)–H activation reactions of aliphatic carboxylic acids, amides, and ketones were developed for efficient access to DEL synthesis.
Abstract The palladium(II)‐catalyzed β‐ and γ‐alkynylation of amide C(sp 3 )−H bonds is enabled by pyridine‐based ligands. This alkynylation reaction compatible with substrates containing α‐tertiary or α‐quaternary carbon centers. β‐methylene various carbocyclic rings were also successfully alkynylated.
Abstract A novel bidentate α‐amino oxazolinyl directing group has been developed. Different from previous groups, this newly designed was easily prepared amino acids and modified in structure. This auxiliary preferentially effects functionalization at secondary C(sp 3 )H bonds, rather than aryl 2 bonds. The diastereoselectivity of direct arylation between geminal bonds linear molecules also realized for the first time with a chiral by remote chirality relay. Two diastereoisomers are...
Abstract Pd II ‐catalyzed enantioselective C(sp 3 )−H cross‐coupling of free carboxylic acids with organoborons has been realized using either mono‐protected amino acid (MPAA) ligands or aminoethyl amine (MPAAM) ligands. A diverse range aryl‐ and vinyl‐boron reagents can be used as coupling partners to provide chiral acids. This reaction provides an alternative approach the synthesis cyclopropanecarboxylic cyclobutanecarboxylic containing α‐chiral tertiary quaternary stereocenters. The...
The palladium(II)-catalyzed β- and γ-alkynylation of amide C(sp3)−H bonds is enabled by pyridine-based ligands. This alkynylation reaction compatible with substrates containing α-tertiary or α-quaternary carbon centers. β-methylene various carbocyclic rings were also successfully alkynylated.
DNA-encoded library (DEL) technology has the potential to dramatically expedite hit identification in drug discovery owing its ability perform protein affinity selection with millions or billions of molecules a single experiment. To expand molecular diversity DEL, it is critical develop different types transformations that produces distinct scaffolds. Sequential functionalization multiple C–H bonds provides unique avenue for creating and complexity from simple starting materials. However,...
We report the development of Pd(II)-catalyzed C(sp 3 )–H arylation Weinreb amides. A pyridinesulfonic acid ligand is designed to accommodate weak, neutral coordinating property amides via preserving cationic character Pd center through zwitterionic assembly Pd/ligand complexes. DFT studies C–H cleavage step indicate that superior reactivity 3-pyridinesulfonic compared pyridine, Ac-Gly-OH, and ligandless conditions originates from stabilization overall substrate-bound species.
<em> </em><p>We report the development of Pd(II)-catalyzed C(sp<sup>3</sup>)–H arylation Weinreb amides. A pyridinesulfonic acid ligand is designed to accommodate weak, neutral coordinating property amides via preserving cationic character Pd center through zwitterionic assembly Pd/ligand complexes. DFT studies C–H cleavage step indicate that superior reactivity 3-pyridinesulfonic compared pyridine, Ac-Gly-OH, and ligandless conditions originates from...