Buchwald–Hartwig amination

Buchwald-Hartwig amination
Named after	Stephen L. Buchwald John F. Hartwig
Reaction type	Coupling reaction
Identifiers
Organic Chemistry Portal	buchwald-hartwig-reaction
RSC ontology ID	RXNO:0000192

The Buchwald–Hartwig amination is a chemical reaction used in organic chemistry for the synthesis of carbon–nitrogen bonds via the palladium-catalyzed cross-coupling of amines with aryl halides. Although Pd-catalyzed C-N couplings were reported as early as 1983, credit for its development is typically assigned to Stephen L. Buchwald and John F. Hartwig, whose publications between 1994 and the late 2000s established the scope of the transformation. The reaction's synthetic utility stems primarily from the shortcomings of typical methods (nucleophilic substitution, reductive amination, etc.) for the synthesis of aromatic C–N bonds, with most methods suffering from limited substrate scope and functional group tolerance. The development of the Buchwald–Hartwig reaction allowed for the facile synthesis of aryl amines, replacing to an extent harsher methods (the Goldberg reaction, nucleophilic aromatic substitution, etc.) while significantly expanding the repertoire of possible C–N bond formation.

 

 

 

 

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Over the course of its development, several 'generations' of catalyst systems have been developed, with each system allowing greater scope in terms of coupling partners and milder conditions, allowing virtually any amine to be coupled with a wide variety of aryl coupling partners. Because of the ubiquity of aryl C-N bonds in pharmaceuticals and natural products, the reaction has gained wide use in synthetic organic chemistry, finding application in many total syntheses and the industrial preparation of numerous pharmaceuticals. Several reviews have been published.

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