Synthesis of Primary Amines / Hydrazines via Buchwald-Hartwig Amination
Mechanism + Description
Mechanism as for Pd catalysed B-H amination for secondary and tertiary amines.
Primary amines can be constructed using B-H amination methodology. Initially, ammonia equivalents like HN(TMS)2 or benzophenone imine were used followed by deprotection to reveal the primary amine. Catalyst systems have now been identified that work with NH3 directly thus making this transformation more mass efficient. Likewise, aryl/heteroaryl hydrazines can be prepared from benzophenone hydrazone, or with certain ligands, N2H4 directly.
Relevant scale up examples with Scheme
Org. Process Res. Dev., 2006, 10, 70-77
7 kg scale
Org. Process Res. Dev., 2014, 18 (12), 1752–1758
1 kg scale
Org. Process Res. Dev., 2008, 12, 512–521
8 kg scale