A5077027092- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
- Catalytic Alkyne Reactions
- Crystallization and Solubility Studies
- Catalytic C–H Functionalization Methods
- X-ray Diffraction in Crystallography
- Catalytic Cross-Coupling Reactions
- Asymmetric Hydrogenation and Catalysis
- Organoboron and organosilicon chemistry
- Innovative Microfluidic and Catalytic Techniques Innovation
- Synthesis and Catalytic Reactions
- Coordination Chemistry and Organometallics
- Chemical synthesis and alkaloids
- Axial and Atropisomeric Chirality Synthesis
- Fluorine in Organic Chemistry
- Chemical Synthesis and Reactions
- Sulfur-Based Synthesis Techniques
- Marine Sponges and Natural Products
- Crystallography and molecular interactions
- Synthesis and Reactions of Organic Compounds
- Synthesis of heterocyclic compounds
- Chemical Reaction Mechanisms
- Advanced Synthetic Organic Chemistry
- Cyclopropane Reaction Mechanisms
Agios Pharmaceuticals (United States)
2024
Boehringer Ingelheim (United States)
2012-2023
Boehringer Ingelheim (United Kingdom)
2016-2018
Ridgewood Public Schools
2016-2018
Stanford University
2003-2016
Boehringer Ingelheim (Germany)
2009-2014
University of California, San Diego
2003
Abstract Catalysis has become increasingly important for the pharmaceutical industry. is a critical technology that enables economical and environmentally‐sound manufacturing processes. The development of viable catalytic process industrial scales complex task requires collaboration multiple disciplines. In this article, number selected, noteworthy examples are discussed to showcase technologies have been successfully practiced on large active ingredient (API) synthesis, involving transition...
The dynamic kinetic asymmetric allylic alkylations of racemic allene acetates has been developed with the DACH−phenyl Trost ligand 2 to give general access allenes high enantiomeric excess (84−95%) for both malonate and amine nucleophiles. Further, a most unusual dependence enantioselectivity on base uncovered. magnitude is heavily dependent nucleophiles, but sense induction A Rh(I)-catalyzed intramolecular [4 + 2] cycloaddition DYKAT products was accomplished afford formal Diels−Alder...
Aryltrimethylammonium triflates and tetrafluoroborates were found to be highly reactive electrophiles in the Pd-catalyzed cross coupling with aryl Grignard reagents. The reactions proceed at ambient temperature a nearly stoichiometric quantity of reagent, diverse functionality is tolerated. Competition experiments established reactivity PhNMe(3)OTf relative PhCl, PhBr, PhI, PhOTf.
COSMO-RS and machine learning-based models can reduce the cost of screening identifying crystal coformers, facilitating discovery new cocrystals.
The first examples of the use racemic vinylaziridines in a Pd-catalyzed dynamic kinetic asymmetric transformation have been examined. Optimization studies addition to isocyanates revealed that chiral ligand between trans-1,2-diaminocyclohexane and 2-diphenylphosphino-1-naphthoic acid is superior involving 2-diphenylphosphino benzoic acid. Surprisingly, high ee's required an whose pKa was about 4.7 +/- 0.1 as cocatalyst. Both acetic hydroxybenzotriazole meet this requirement. Less...
The highly enantio- and regioselective copper catalyzed asymmetric propargylation of aldehydes with a propargyl borolane reagent is reported. methodology demonstrated broad functional group tolerance provided high enantioselectivities for aliphatic, vinyl, aryl aldehydes. utility the TMS homopropargylic alcohols was by facile conversion to chiral dihydropyranone.
We report the development of a new class guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in remote desymmetrization diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design these peptides, high levels enantioinduction good isolated yields were achieved long-range asymmetric cross-coupling (up to 93:7 er 76% yield) between aryl bromides malonates. Our mechanistic studies suggest that distal stereocontrol is through...
A concise total synthesis of (+)-pseudodistomin D was developed. The absolute stereochemistry established through a dynamic kinetic asymmetric cycloaddition an isocyanate to vinyl aziridine. piperidine core constructed silver(I)-catalyzed hydroamination alkyne and subsequent diastereo- regioselective reduction.
An atom-economical method has been developed for the preparation of chiral vicinal diamines through a dynamic kinetic asymmetric allylic amination and acyl-group migration vinyl aziridines with imido carboxylates. Application transformation enabled concise synthesis azepane core 1 (+)-balanol its syn analogue.
In the presence of catalytic CuI and sparteine, 2-formylpyrroles can be annulated with o-aminoiodoarenes to give substituted pyrrolo[1,2-a]quinoxalines related heterocycles. The reaction also works for annulation 2-formylindoles, 2-formylimidazole, 2-formylbenzimidazole, a 3-formylpyrazole.
An operationally simple copper-BINAP-catalyzed, highly enantioselective propargylation of ketones is presented. The methodology was developed as an process for methyl ethyl ketone and shown to be applicable a wide variety prochiral ketones. resulting homopropargyl adducts are versatile latent carbonyls from which γ-butyrolactones, β-hydroxy ketones, β-hydroxycarboxylates readily obtained.
The copper-catalyzed asymmetric propargylation of cyclic aldimines is reported. influence the imine trimer to inhibit reaction was identified, and equilibrium constants between monomer were determined for general classes imines. Asymmetric a diverse series N-alkyl N-aryl achieved with good high induction. utility demonstrated by titanium catalyzed hydroamination reduction generate chiral indolizidines (−)-crispine A (−)-harmicine.
This review article summarizes C-H functionalization-based synthesis of indoles and related structures (e.g.carbazoles indolines) with an emphasis on literature after 2000.The discussion is organized into four broadly defined sections: a) via nitrene or carbene insertion a bond; b) direct coupling two sp 2 carbon centers; c) transition-metal catalyzed amination d) other strategies.
N-Heterocyclic carbenes (NHCs) were found to catalyze the silyl transfer from trialkylsilyl ketene acetals ketones. In presence of a catalytic amount NHC 3 (IAd, 0.1 5 mol %), series enolizable ketones as well cyclohexanecarboxaldehyde efficiently converted into corresponding enol ethers at 23 °C in THF.
A zinc-catalyzed diastereoselective propargylation of t-butanesulfinyl imines is presented. The methodology provided both aliphatic and aryl homopropargylic amines in up to 98:2 99.8:0.2 dr, respectively. utility the was demonstrated by application synthesis a cis-substituted pyrido-indole through Pictet-Spengler cyclization.
The development of zinc-mediated and -catalyzed asymmetric propargylations trifluoromethyl ketones with a propargyl borolane the N-isopropyl-l-proline ligand is presented. methodology provided moderate to high stereoselectivity was successfully applied on multikilogram scale for synthesis Glucocorticoid agonist BI 653048. A mechanism boron–zinc exchange proposed supported by modeling at density functional level theory. water acceleration effect zinc-catalyzed propargylation discovered, which...
Synthesis of the electron-rich 2-substituted-6-(phenylsulfonyl)pyridines is presented. A series air-stable, tunable, P-chiral pyridyl-dihydrobenzooxaphosphole ligands were designed and synthesized by a diastereoselective SNAr substitution corresponding sulfonyl pyridines. The successfully applied in Ir-catalyzed asymmetric hydrogenation unfunctionalized alkenes with good enantioselectivities.
The utility of allenyl and propargyl boronates for the propargylation aldehydes ketones mediated by zinc is presented. reaction catalytic in with or borolanes. crystalline air-stable diethanolamine was also achieved. A cycle proposed, preliminary mechanistic studies are discussed.
The general zinc-catalyzed allenylation of aldehydes and ketones with an allenyl boronate is presented. Preliminary mechanistic studies support a kinetically controlled process wherein, after site-selective B/Zn exchange to generate propargyl zinc intermediate, the addition electrophile effectively competes propargyl-allenyl equilibration. utility methodology was demonstrated by application rhodium-catalyzed [4+2] cycloaddition.
Lasonolide A is a novel polyketide displaying potent anticancer activity across broad range of cancer cell lines. Here, an enantioselective convergent total synthesis the (-)-lasonolide in 16 longest linear and 34 steps described. This approach significantly reduces step count compared to other known syntheses. The synthetic strategy utilizes alkyne-bearing substrates as core building blocks highlighted by stitching together two similarly complex halves via key Ru-catalyzed alkene-alkyne...
The development of a large scale synthesis the glucocorticoid agonist BI 653048 BS H3PO4 (1·H3PO4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by enolization/bromine–magnesium exchange/electrophile trapping reaction. nonselective propargylation gave desired diastereomer in 32% yield and with dr = 98:2 from 1:1 diastereomeric mixture after crystallization. Subsequently, asymmetric developed which provided 4:1...
The lasonolides are novel polyketides that have displayed remarkable biological activity in vitro against a variety of cancer cell lines. Herein we describe our first-generation approach to the formal synthesis lasonolide A. key findings from these studies ultimately allowed us go on and complete total convergent unites two highly complex fragments utilizing Ru-catalyzed alkene-alkyne coupling. This type coupling typically generates branched products; however, through detailed investigation,...
Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires prefunctionalized building blocks. However, the requisite prefunctionalization steps undermine overall efficiency of synthetic sequences that rely on such reactions, which is particularly problematic large-scale applications, as commercial production pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without In this transformation several classes unactivated...