[Skip to Content](https://www.sigmaaldrich.com#main-content) [![MilliporeSigma](https://www.sigmaaldrich.com/static/logos/purple/millipore_sigma.svg)](https://www.sigmaaldrich.com/US/en) Products Cart0 USEN Products [Login / Register](https://www.sigmaaldrich.com/oidc-sign-in) [Order Lookup](https://www.sigmaaldrich.com/US/en/order-lookup) [Quick Order](https://www.sigmaaldrich.com/US/en/quick-order) Cart0 [Home](https://www.sigmaaldrich.com/US/en)[Cross-Coupling](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/cross-coupling)Willis Pyridinates for Palladium-Catalyzed Cross-Coupling Reactions # Willis Pyridinates for Palladium-Catalyzed Cross-Coupling Reactions ## Introduction The Suzuki-Miyaura cross-coupling reaction is one of the most used transformations in the pharmaceutical industry to form carbon-carbon bonds.1,2 However, limitations to the application of this reaction in discovery chemistry persist, including the notorious low reaction efficiency, poor stability, and difficulty in preparing pyridine-2-boronates and boronic acids for cross-coupling. __Read more about__ - [Representative Scheme and Examples](https://www.sigmaaldrich.com#representative-scheme-examples) - [Advantages](https://www.sigmaaldrich.com#advantages) - [References](https://www.sigmaaldrich.com#references) [Related Materials](https://www.sigmaaldrich.com#related-materials) Professor Willis and industrial partners at Pfizer have shown that by replacing boronates with pyridine-2-sulfinates as nucleophilic coupling partners, a palladium-catalyzed desulfinylative cross-coupling process of exceptional scope can be realized.3 Both aryl bromides and aryl chlorides can be employed as coupling partners to access challenging and medicinally relevant linked pyridine-heterocycle building blocks. ![Six chemical structures, each with a unique product number below them. The structures are variations of benzene rings with different functional groups attached, such as amine (NH2), sulfonate (SO3Na), methyl (CH3), fluorine (F), and ketone (C=O). The product numbers are 900757, 900762, 900760, 900759, 900763, and 900760. ](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/chemistry-and-synthesis/cross-coupling/ts-willis-pyridinates-fig1.jpg "ts-willis-pyridinates-fig1") ## [](https://www.sigmaaldrich.com)Representative Scheme and Examples ![A series of chemical reactions showcasing the use of Willis Pyridinates in Palladium-Catalyzed Cross-Coupling Reactions. At the top, a reaction scheme illustrates the transformation of a pyridine sulfinate compound to various substituted pyridines using Pd(OAc)2 as a catalyst, XPhos as a ligand, and K2CO3 as a base in 1,4-dioxane at 150°C. Below are six examples of this reaction with different substituents on the pyridine ring and their corresponding yields, one notably being 92% with an annotation of ‘6.9 grams’. Each product is depicted with clear molecular structures indicating the position and type of substituents like fluorine atoms or methoxy groups.](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/chemistry-and-synthesis/cross-coupling/ts-willis-pyridinates-fig2.jpg "ts-willis-pyridinates-fig2") ## [](https://www.sigmaaldrich.com)Advantages - Bench-stable, solid reagents - Efficient nucleophilic cross-coupling partners - Convenient removal during aqueous work-up Special thanks to Tim Markovic and [Prof. Michael Willis](https://www.sigmaaldrich.com/US/en/collections/professor-product-portal/willis) for contributing this Technology Spotlight! ## Related Materials Sorry, an unexpected error has occurred Response not successful: Received status code 500 ### References 1\. Miyaura N, Yamada K, Suzuki A. 1979. A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides. Tetrahedron Letters. 20(36):3437-3440. [https://doi.org/10.1016/s0040-4039(01)95429-2](https://doi.org/10.1016/s0040-4039%2801%2995429-2) 2\. 2016\. [https://doi.org/10.1039/9781782622086](https://doi.org/10.1039/9781782622086) 3\. Markovic T, Rocke BN, Blakemore DC, Mascitti V, Willis MC. Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides. Chem. Sci.. 8(6):4437-4442. 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