ring-closing metathesis

ring-closing metathesis
Name	Ring-closing metathesis
Type	Organic reaction
Catalyst	Grubbs catalysts, Schrock catalysts
Substrate	Dienes, enynes
Product	Cycloalkenes

ring-closing metathesis

Ring-closing metathesis is an organic transformation that converts dienes or enynes into cyclic alkenes using metal alkylidene catalysts, with broad utility across University of California, Berkeley research groups, ETH Zurich laboratories, and industrial settings such as BASF and DSM. Developed through work at institutions including California Institute of Technology, Massachusetts Institute of Technology, and Columbia University, the method has been influential in total syntheses undertaken by teams from Scripps Research Institute and Harvard University. Award recognition for pioneers working on olefin metathesis includes linkage to honors associated with Nobel Prize–level achievements and to laboratories previously affiliated with the Max Planck Society.

Introduction

Ring-closing metathesis was popularized by researchers at AbbVie collaborations and by groups at Ecole Polytechnique Fédérale de Lausanne and University of California, Los Angeles, becoming a standard tactic in synthetic campaigns by teams at Pfizer and GlaxoSmithKline. Historical milestones trace through laboratories led by figures associated with California Institute of Technology and Cornell University chemistry departments, and the technique became widely disseminated via conferences organized by American Chemical Society and symposia at Royal Society of Chemistry. Early commercial adoption involved reagent suppliers such as Sigma-Aldrich and instrumentation manufacturers like Agilent Technologies.

Mechanism and Catalysts

Mechanistic framework draws on metal carbene chemistry developed in groups at Brunel University and University of Manchester, relying on [2+2] cycloaddition and cycloreversion sequences studied in laboratories affiliated with Imperial College London and Tokyo Institute of Technology. Ruthenium-based catalysts like those from the Grubbs lineage were optimized in collaborations between California Institute of Technology and companies such as MilliporeSigma, while molybdenum and tungsten systems trace to work at Yale University and University of California, Santa Barbara. Synthetic practitioners at University of Oxford and University of Cambridge often choose ruthenium complexes for functional group tolerance, whereas researchers from Northwestern University and University of Illinois Urbana-Champaign exploit Schrock-type catalysts for electron-poor substrates. Catalyst design has been influenced by industrial projects at DuPont and academic projects linked to ETH Zurich.

Scope and Synthetic Applications

Applications span macrocyclization efforts in natural product syntheses by groups at Scripps Research Institute and Princeton University, including work on alkaloids pursued by teams from University of Tokyo and University of California, San Diego. Small-ring and medium-ring formations are routine in medicinal chemistry programs at Merck & Co. and AstraZeneca, while complex polycyclic assemblies have been reported by researchers at Johns Hopkins University and University of California, Irvine. Total syntheses utilizing the transformation have been communicated by scientists at Columbia University, University of Pennsylvania, and Vanderbilt University, and methodology extensions appear in publications from Duke University and University of Wisconsin–Madison.

Selectivity and Stereocontrol

Control over E/Z geometry has been explored by teams at Princeton University and Scripps Research Institute, and stereochemical outcomes are routinely optimized by groups within Harvard University and Stanford University. Approaches that modulate ring size and substitution patterns are informed by studies at University of Michigan and Brown University, while computational investigations from Massachusetts Institute of Technology and University of Chicago aid predictive models of selectivity. Diastereoselective and enantioselective variants have been developed in research programs at University of California, Davis and University of North Carolina at Chapel Hill working alongside collaborators at Eli Lilly and Company.

Limitations and Common Side Reactions

Limitations include oligomerization and cross-metathesis pathways noted in case studies from Bayer and Sanofi, and catalyst decomposition pathways were characterized by scientists at Cornell University and University of Florida. Functional group incompatibilities were mapped by researchers at University of Basel and University of Zurich, and competing isomerization phenomena have been reported in methodological papers from University of Notre Dame and University of Göttingen. Strategies to mitigate side reactions were trialed by teams at Rensselaer Polytechnic Institute and Wageningen University & Research.

Experimental Conditions and Procedures

Typical procedures are documented in protocols used at Scripps Research Institute and taught in laboratory courses at Massachusetts Institute of Technology and University of California, Berkeley, with solvents and inert-atmosphere technique supplied by vendors such as Fisher Scientific and VWR. Reaction setup and scale-up considerations are addressed in engineering groups at AstraZeneca and Pfizer, whereas analytical monitoring using equipment from Thermo Fisher Scientific and Bruker supports process control. Additives and ligand variations developed by teams at Karolinska Institutet and Weizmann Institute of Science tune reactivity and turnover numbers.

Industrial and Pharmaceutical Applications

Industrial integration into active pharmaceutical ingredient syntheses has been implemented by GlaxoSmithKline and Merck & Co., with process research contributions from Roche and Novartis. Macrocyclization strategies enabled by the transformation underpin drug discovery programs at Bristol-Myers Squibb and Eli Lilly and Company, and scale-up case studies are available from operations at BASF and DuPont. Collaborations between academic centers such as ETH Zurich and companies like Johnson & Johnson have advanced catalyst technologies toward commercial viability, while regulatory considerations are addressed by professionals with experience at European Medicines Agency and U.S. Food and Drug Administration.

Category:Organic reactions