A5020483254- Asymmetric Synthesis and Catalysis
- Asymmetric Hydrogenation and Catalysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Catalytic C–H Functionalization Methods
- Catalytic Cross-Coupling Reactions
- Synthetic Organic Chemistry Methods
- Organophosphorus compounds synthesis
- Fluorine in Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Cyclopropane Reaction Mechanisms
- Crystallography and molecular interactions
- Chemical Synthesis and Reactions
- Axial and Atropisomeric Chirality Synthesis
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Chemical synthesis and alkaloids
- Inorganic Fluorides and Related Compounds
- Radical Photochemical Reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Synthesis and Catalytic Reactions
- Synthesis and Reactions of Organic Compounds
- Coordination Chemistry and Organometallics
- Molecular Junctions and Nanostructures
- Advanced Synthetic Organic Chemistry
Pfizer (United States)
2020-2025
Boehringer Ingelheim (United States)
2013-2022
Boehringer Ingelheim (Taiwan)
2016-2018
Ridgewood Public Schools
2016-2018
Boehringer Ingelheim (India)
2018
Colorado State University
2018
Columbia University
2018
University of Chicago
2018
California Institute of Technology
2018
Leibniz Institute for Catalysis
2018
Abstract Recent studies have demonstrated that amides can be used in nickel‐catalyzed reactions lead to cleavage of the amide C−N bond, with formation a C−C or C−heteroatom bond. However, general scope these methodologies has been restricted where carbonyl is directly attached an arene heteroarene. We now report esterification derived from aliphatic carboxylic acids. The transformation requires only slight excess alcohol nucleophile and tolerant heterocycles, substrates epimerizable...
Synthesis of chiral sulfones: A copper–phosphine complex efficiently provided optically active alkyl phenyl sulfones by hydrosilylation at room temperature. The reduction β,β-disubstituted vinyl in the presence Me-DuPhos monoxide ligand lead to excellent enantiomeric excesses and high yields (see scheme). prepared were desulfonylated subjected Julia olefination conditions.
A general, efficient, and highly diastereoselective method for the synthesis of structurally sterically diverse P-chiral phosphine oxides was developed. The relies on sequential nucleophilic substitution versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced differentiated P-N P-O bond reactivity toward nucleophiles. reactivities both bonds are fine-tuned to allow cleavage occur even with hindered nucleophiles under mild conditions.
A highly enantioselective acylation of silyl ketene acetals with acyl fluorides has been developed to generate useful α,α-disubstituted butyrolactone products. This transformation is promoted by a new thiourea catalyst and 4-pyrrolidinopyridine represents the first example anion-binding catalysis fluoride.
The use of chiral phosphinamides is relatively unexplored because the lack a general method for synthesis. Reported herein development general, efficient, and highly enantioselective synthesis structurally diverse P-stereogenic phosphinamides. relies on nucleophilic substitution phosphinate derived from versatile phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide. These were utilized first readily tunable Lewis base organocatalysts, which used successfully catalysis.
Abstract A nickel‐catalyzed Heck cyclization for the construction of quaternary stereocenters is reported. This transformation demonstrated in synthesis 3,3‐disubstituted oxindoles, which are prevalent motifs seen numerous biologically active molecules. The method shows broad scope, proceeds synthetically useful yields, and provides a rare means to construct stereochemically complex frameworks by nonprecious‐metal catalysis.
A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access previously unobtainable, biologically relevant α-quaternary amino derivatives starting from readily available precursors.
The development of enantioselective carbon-carbon bond couplings catalyzed by nonprecious metals is highly desirable in terms cost efficiency and sustainability. first nickel-catalyzed Mizoroki-Heck coupling reported. This transformation accomplished via mild reaction conditions, leveraging on QuinoxP* as a chiral ligand to afford oxindoles containing quaternary stereocenters. Good reactivity selectivity are observed the presence various functional groups. Computational studies suggest that...
Enantioselective synthesis of α-aryl and α-heteroaryl piperidines is reported. The key step an iridium-catalyzed asymmetric hydrogenation substituted N-benzylpyridinium salts. High levels enantioselectivity up to 99.3:0.7 er were obtained for a range piperidines. DFT calculations support outersphere dissociative mechanism the pyridinium reduction. Notably, initial protonation final enamine intermediate determines stereochemical outcome transformation rather than hydride reduction resultant...
An Ir-catalyzed enantioselective hydrogenation of 2-alkyl-pyridines has been developed using ligand MeO-BoQPhos. High levels enantioselectivities up to 93:7 er were obtained. The resulting enantioenriched piperidines can be readily converted into biologically interesting molecules such as the fused tricyclic structures 5, 6, and 7 in 99:1 er, providing a novel, concise synthetic route this family chiral piperidine-containing compounds.
A new class of tunable heterophosphole dimeric ligands have been designed and synthesized. These enabled the first examples Cu-catalyzed hydrogenation 2-substituted-1-tetralones related heteroaryl ketones via dynamic kinetic resolution, simultaneously creating two contiguous stereogenic centers with up to >99 : 1 dr 98 2 er. The ligand-Cu complexes were isolated characterized by single crystal X-ray, DFT calculations revealed a novel heteroligated copper hydride transition state.
A concise asymmetric synthesis of an 11β-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total 1 was accomplished in 7 steps and 38% overall yield aided by the development innovative, sequential strategy involving Pd-catalyzed pyridinium C-H arylation Ir-catalyzed hydrogenation resulting fused tricyclic indenopyridinium salt highlighted use a unique P,N-ligand (MeO-BoQPhos) 1000 ppm...
An electrochemical method has been developed for a mediated oxidation of primary alcohols to carboxylic acids. The is compatible with variety bearing nitrogen-containing heterocycles in undivided batch and flow modes. use heterogeneous NiOOH electron–proton transfer mediator avoids the need homogeneous catalysts that contribute more unit operations during downstream purging increased process mass intensity. To demonstrate applicability this continuous processing, single-pass nicotinyl...
Abstract Air‐stable P‐chiral dihydrobenzooxaphosphole oxazoline ligands were designed and synthesized. When they used in the iridium‐catalyzed asymmetric hydrogenation of unfunctionalized 1‐aryl‐3,4‐dihydronaphthalenes under one atmosphere pressure H 2 , up to 99:1 e.r. was obtained. High enantioselectivities also observed reduction exocyclic imine derivatives 1‐tetralones.
A scalable electrochemical procedure for the synthesis of carboxylic acids from organic halides has been developed using a spinning cylinder electrode reactor. The process is based on reductive dehalogenation starting material followed by trapping resulting carbanion with CO2. protocol compatible both chlorides and bromides uses inexpensive graphite stainless steel as materials. As sacrificial metal anodes are avoided, method can be readily scaled up in flow mode. wide range substrates (24...
An efficient method for the catalytic asymmetric conjugate addition of diorganozinc reagents to vinyl sulfones is reported. Using a Binap•Cu complex, enantioselectivities up 98% ee and high yields can be attained variety substrates. Several dialkylzinc are also compatible with this procedure.
Recent studies have demonstrated that amides can be used in nickel-catalyzed reactions lead to cleavage of the amide C−N bond, with formation a C−C or C−heteroatom bond. However, general scope these methodologies has been restricted where carbonyl is directly attached an arene heteroarene. We now report esterification derived from aliphatic carboxylic acids. The transformation requires only slight excess alcohol nucleophile and tolerant heterocycles, substrates epimerizable stereocenters,...
Biocatalytic reductive amination catalyzed by engineered imine reductase (RedAms) is a new and powerful tool for the synthesis of substituted chiral amines. Herein, we describe streamlined compound 3, key intermediate to CDK 2/4/6 inhibitor 1, relying on enzymatic hydroxyketone introduce secondary amine with high diastereoselectivity. The improved precursor titanium-catalyzed cyclization process development two SNAr reactions en route 3 are also presented.
Electrochemical synthesis of a key thiol intermediate in the preparation axitinib has been achieved on multi-10 g scale using modified spinning cylinder electrode reactor adapted for "quasi-divided" cell operation. This concept enables target cathodic reduction to occur without need sacrificial electrodes or divided cells equipped with ion exchange membranes. The new design, based scalable platform, features an inner cathode made leaded bronze and vessel which variable number...
A commercial process for vepdegestrant (1), the most advanced PROTAC protein degrader in human clinical trials, has been developed to support and needs. The features an efficient convergent synthetic strategy through final reductive amination of two chiral intermediates, as well several highly telescoped processes robust crystallization purity control. (1) consists seven proposed regulatory GMP steps with five isolations overall yield 29%.
[reaction: see text] The stereoselective displacement of a variety chiral benzylic alcohols with triethylmethanetricarboxylate (TEMT) under Mitsunobu conditions (DEAD, PMe(3)) has been demonstrated to proceed in good yield (70-94%) and high degree inversion. Subsequent saponification decarboxylation the products thus obtained provide 3-aryl-3-substituted propanoic acids without racemization.
5-Cyanoimidazole was identified as an inexpensive ligand for nickel-catalyzed cross-electrophile couplings by screening a diverse set of pharmaceutical compound library. A strategic approach led to the discovery this novel ligand, which successfully applied in preparation various alkylated arene products with good high yields. Furthermore, properties allowed expanding scope reductive challenging substrates, such sterically hindered neopentyl halides, are known generate motifs that prevalent...
Abstract The copper-catalyzed diorganozinc addition to N -diphenylphosphinoylimines was shown proceed with a very high degree of enantiocontrol if the reaction run in presence Me-DuPHOS monoxide ligand (BozPHOS). scope is described as well our efforts identify nature enantioactive metal complex responsible for asymmetric induction.