Organic Small Molecule Catalyzed Carbonylation Reactions

Abstract

C1 chemistry is important from both academia research and industrial application which are extensively studied with metal catalysts. Considering the advantages of organic small molecule catalysts, it's super attractive to explore them as catalyst in carbonylation chemistry. This Review examines organic small molecule catalyzed carbonylation from advanced catalysis perspective, with particular emphasis on N-heterocyclic carbene (NHC) catalysis, oxygen, sulfur, selenium, nitrogen and phosphines main-group species-based catalysts further expand the conceptual and synthetic landscape of sustainable carbonylation. These advances define carbonylation as a catalyst designed reaction class and highlight opportunities for future organic small molecule driven development.Carbonylation reactions constitute a powerful toolbox in modern synthetic chemistry because they provide a direct and atom-economic entry to carbonyl functionalities that permeate pharmaceuticals, natural products, agrochemicals and functional materials 1 . According to FDA statistics from 2015 to 2020, approximately 80% of approved drugs contain carbonyl functional groups (Fig 1 .1a) 2 . For example, the widely prescribed anticoagulant Eliquis (ranked second in 2024 retail drug sales for thrombosis prevention) and the anti-myeloma agent Revlimid (ranked 28th) each contain three or more carbonyl groups and achieved market values of $20.699 billion and $5.809 billion, respectively 3 . In synthetic chemistry, carbonylation technologies are among the most efficient and atom-economical methods for constructing carbonyl compounds 4-8 : these processes convert carbon monoxide (CO)-derived from coal, natural gas or biomass-into value-added carbonylated products with essentially 100% atom utilization 9 . CO is thus recognized as an abundant, cost-effective and versatile C1 feedstock in carbonylation chemistry. A canonical industrial example is the methanol carbonylation to acetic acid embodied by the Monsanto and Cativa processes, which together underpin the production of a substantial fraction of the world's acetic acid 10,11 .1) Advanced Carbonylation Process and the Value of Carbonyl-Containing Motifs80% 20%