A5017656147- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Catalytic C–H Functionalization Methods
- Asymmetric Hydrogenation and Catalysis
- Catalytic Cross-Coupling Reactions
- Synthesis and Catalytic Reactions
- Nanomaterials for catalytic reactions
- Radical Photochemical Reactions
- Oxidative Organic Chemistry Reactions
- Cyclopropane Reaction Mechanisms
- Sulfur-Based Synthesis Techniques
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Biochemical and Structural Characterization
- Optimal Experimental Design Methods
- Manufacturing Process and Optimization
- Biochemical and Molecular Research
- Crystallography and molecular interactions
- Advanced Statistical Process Monitoring
- Organometallic Compounds Synthesis and Characterization
- Drug Solubulity and Delivery Systems
- Organometallic Complex Synthesis and Catalysis
- Metal complexes synthesis and properties
- Catalysts for Methane Reforming
- Click Chemistry and Applications
Gilead Sciences (United States)
2021-2025
University of Münster
2016-2019
Massachusetts Institute of Technology
2013-2018
IIT@MIT
2013-2015
Boise State University
2012
ConspectusNickel(0) catalysts have proven to be powerful tools for multicomponent coupling reactions in our laboratories over the past 15 years. This interest was originally sparked by ubiquity of allylic alcohol motifs natural products, such as (–)-terpestacin, which we envisioned assembling two π components (alkyne and aldehyde) with concomitant reduction. Mechanistic investigations allowed us elucidate several modes controlling regioselectivity stereoselectivity oxidative cyclization,...
A series of air-stable nickel complexes the form L2Ni(aryl) X (L = monodentate phosphine, Cl, Br) and LNi(aryl)X bis-phosphine) have been synthesized are presented as a library precatalysts suitable for wide variety nickel-catalyzed transformations. These easily from low-cost NiCl2·6H2O or NiBr2·3H2O desired ligand followed by addition 1 equiv Grignard reagent. selection these were characterized single-crystal X-ray diffraction, an analysis their structural features is provided. case study...
The synthesis and characterization of the air-stable nickel(II) complex trans-(PCy2Ph)2Ni(o-tolyl)Cl is described in conjunction with an investigation its use for Mizoroki–Heck-type, room temperature, internally selective coupling substituted benzyl chlorides terminal alkenes. This reaction, which employs a alkene as alkenylmetal equivalent, provides rapid, convergent access to allylbenzene derivatives high yield regioselectivity greater than 95:5 nearly all cases. reaction operationally...
Herein, we report the first ligand-controlled, nickel-catalyzed cross-coupling of aliphatic N-tosylaziridines with organozinc reagents. The reaction protocol displays complete regioselectivity for at less hindered C-N bond, and products are furnished in good to excellent yield a broad selection substrates. Moreover, have developed an air-stable nickel(II) chloride/ligand precatalyst that can be handled stored outside glovebox. In addition increasing activity this catalyst system, also...
Herein is reported the catalytic, visible light-promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally-simple reaction tolerates a range functional groups, proceeds at room temperature, redox neutral. By employing an iridium photocatalyst in concert with halogen atom source, use stoichiometric metals such as silver, mercury, thallium, lead can be circumvented. grants access to valuable synthetic building blocks...
Significance Combinatorial protein libraries—prepared via molecular biology-based approaches—are invaluable tools for engineering. The inclusion of noncanonical amino acids in such libraries is considerable interest. However, at present no approach competes with chemical synthesis terms the variety and number that can be simultaneously incorporated into a molecule. Here, we describe selection from synthetic as strategy enables identification small (∼30 aa), functional variants comprising...
Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for treatment HIV infection. An early manufacturing route, relying on simulated moving bed (SMB) chromatography separation phosphorus diastereomers, was executed scale to produce multiple batches 1. However, developing alternative synthetic conditions became desirable consideration high production cost, long lead time, and...
This manuscript describes the chemical process development and multi-kilogram synthesis of rovafovir etalafenamide (GS-9131), a phosphonamidate prodrug nucleotide reverse transcriptase inhibitor under investigation for treatment HIV-1 infection. Rovafovir is assembled in four-step sequence beginning from nucleoside core an elaborated alcohol. The assembly starts with decarboxylative elimination β-hydroxyacid to yield corresponding cyclic enol ether, which subsequently coupled functionalized...
Herein we report on the development of an MS tag screening strategy that accelerates discovery photocatalytic reactions. By efficiently combining mechanism- and reaction-based dimensions, respective advantages each were retained, whereas drawbacks inherent to approach could be eliminated. Applying this led a mild photosensitized decarboxylative hydrazide synthesis from mesoionic sydnones carboxylic acids as starting materials.
Abstract Review: 100 refs.
Abstract Procedures are evaluated which allow the reaction of aliphatic aziridine substrates with organozinc reagents.
Abstract Review: 51 refs.
Abstract The title reaction is achieved in the presence of a typical iridium photocatalyst and various substrates are tolerable.