cross metathesis

cross metathesis
Name	Cross metathesis
Caption	General scheme of olefin cross metathesis
Type	Organic reaction
Discovered	20th century
Catalyst	Ruthenium, molybdenum complexes
Conditions	Inert atmosphere, dry solvents

cross metathesis is an organometallic transformation in which two alkenes exchange alkylidene fragments to form new carbon–carbon double bonds. It is a cornerstone reaction in modern synthesis, used extensively in the work of leading chemists and research institutions. Developed and refined through contributions associated with Nobel-recognized discoveries, it underpins methodologies exploited in industrial settings and academic laboratories worldwide.

Introduction

Cross metathesis was developed alongside landmark studies in olefin metathesis that involved laboratories and figures connected with Nobel Prize in Chemistry, Bob Grubbs, Richard Schrock, Yves Chauvin and research centers such as California Institute of Technology, Massachusetts Institute of Technology, Max Planck Society, ETH Zurich and Imperial College London. Early demonstrations benefited from collaborations with companies and institutions like Merck & Co., BASF, Monsanto Company, DuPont, GlaxoSmithKline and Pfizer. The technique gained acceptance through applications reported in journals and conferences involving organizations such as American Chemical Society, Royal Society of Chemistry, International Union of Pure and Applied Chemistry and presentations at meetings like the Gordon Research Conferences.

Mechanism and Catalysts

The catalytic cycle is based on a sequence of metallacyclobutane intermediates and [2+2] cycloaddition/retrocycloaddition steps first rationalized by researchers at institutions including Cornell University, Columbia University, University of California, Berkeley, Stanford University and University of Cambridge. Practical catalysts are dominated by ruthenium carbene complexes developed in laboratories associated with California Institute of Technology and commercialized by firms such as W. R. Grace and Company and Sigma-Aldrich. Alternative molybdenum and tungsten alkylidene systems trace to work at DuPont Research and Istituto di Chimica Organica, with mechanistic insights from groups at ETH Zurich and University of Oxford. Catalyst design often references contributions from groups led by Robert H. Grubbs, Richard R. Schrock, Matthias Beller, Kenneth C. Nicolaou and Nicholas E. Shepherd. Industrial process adaptations have involved teams at ExxonMobil, Shell plc, Bayer AG and Johnson & Johnson.

Scope and Substrate Compatibility

Substrate scope has been expanded through studies at University of Illinois Urbana–Champaign, University of Texas at Austin, University of Pennsylvania, Yale University and Princeton University. Cross metathesis tolerates a range of functional groups when substrates are similar to those utilized in syntheses from laboratories at Scripps Research Institute, University of California, San Diego, University of Wisconsin–Madison and Duke University. Compatibility with heteroatom-containing olefins and complex natural products was demonstrated in collaborations with groups at Scripps Institution of Oceanography, Monash University, University of Melbourne and Seoul National University. Industrial applications for polymer precursors and fine chemicals were developed by Dow Chemical Company, AkzoNobel, Rohm and Haas, Takeda Pharmaceutical Company and Eli Lilly and Company.

Stereoselectivity and Regioselectivity

Work on E/Z selectivity and positional control has involved research from Columbia University, Harvard University, Princeton University, University of California, Los Angeles and Johns Hopkins University. Strategies for stereoretention and stereocontrol emerged from collaborations among groups led by Robert H. Grubbs, Huw Davies, Scott E. Denmark, Eric Jacobsen and Phil S. Baran, with methodology development presented at venues such as Gordon Research Conferences and published through Nature Chemistry, Journal of the American Chemical Society, Angewandte Chemie International Edition and Chemical Communications. Regioselectivity challenges prompted mechanistic studies at University of Manchester, University of Strasbourg, Weizmann Institute of Science and Riken.

Synthetic Applications and Examples

Synthetic applications range from model studies to total syntheses executed at Scripps Research Institute, Harvard University, Columbia University, University of Cambridge and California Institute of Technology. Cross metathesis has been a key step in syntheses reported by groups such as K. C. Nicolaou, E. J. Corey, Barry Trost, Christopher T. Walsh and Andrew Myers, and used in process chemistry from Merck & Co., Pfizer, Novartis, Roche, Sanofi and Johnson & Johnson. Industrial syntheses of agrochemicals and fragrances by Symrise, Givaudan, International Flavors & Fragrances, Bayer CropScience and Syngenta have exploited cross metathesis for efficient fragment coupling. Applications extend to polymer chemistry in work from Massachusetts Institute of Technology, University of Minnesota, ETH Zurich and University of Akron.

Limitations and Challenges

Limitations were highlighted in studies at University of California, Irvine, Northwestern University, University of Notre Dame, Temple University and New York University. Challenges include catalyst decomposition studied by teams at University of Basel, Ecole Polytechnique Fédérale de Lausanne, University of Geneva and McGill University, as well as selectivity issues addressed by researchers at University of Tokyo, Osaka University and Peking University. Scale-up and sustainability concerns prompted process research at BASF, Dow Chemical Company, ExxonMobil and Shell plc, and environmental assessments involving United Nations Environment Programme-related initiatives and industrial consortiums.

Recent Advances and Future Directions

Recent advances arise from collaborations involving California Institute of Technology, ETH Zurich, University of Oxford, Max Planck Society and Weizmann Institute of Science, with new catalysts and flow processes promoted by Carbon, Inc., Ginkgo Bioworks, Moderna, Inc. and startup spinouts from academic groups. Future directions emphasize integration with techniques developed at Lawrence Berkeley National Laboratory, Argonne National Laboratory, Sandia National Laboratories, Oak Ridge National Laboratory and cross-disciplinary programs at National Institutes of Health, European Research Council, Wellcome Trust and Horizon 2020. Emerging themes include enantioselective variants, renewable feedstocks collaborations involving IKEA, Unilever, Cargill and Archer Daniels Midland Company, and educational dissemination through organizations such as Royal Society, American Association for the Advancement of Science, Royal Society of Chemistry and Chemical Heritage Foundation.

Category:Organic reactions