136834-95-2Relevant academic research and scientific papers
Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles
McNally, Andrew,Haffemayer, Benjamin,Collins, Beatrice S. L.,Gaunt, Matthew J.
, p. 129 - 133 (2014)
The development of new chemical transformations based on catalytic functionalization of unactivated C-H bonds has the potential to simplify the synthesis of complex molecules dramatically. Transition metal catalysis has emerged as a powerful tool with which to convert these unreactive bonds into carbon-carbon and carbon-heteroatom bonds, but the selective transformation of aliphatic C-H bonds is still a challenge. The most successful approaches involve a 'directing group', which positions the metal catalyst near a particular C-H bond, so that the Ca ?'H functionalization step occurs via cyclometallation. Most directed aliphatic C-H activation processes proceed through a five-membered-ring cyclometallated intermediate. Considering the number of new reactions that have arisen from such intermediates, it seems likely that identification of distinct cyclometallation pathways would lead to the development of other useful chemical transformations. Here we report a palladium-catalysed C-H bond activation mode that proceeds through a four-membered-ring cyclopalladation pathway. The chemistry described here leads to the selective transformation of a methyl group that is adjacent to an unprotected secondary amine into a synthetically versatile nitrogen heterocycle. The scope of this previously unknown bond disconnection is highlighted through the development of C-H amination and carbonylation processes, leading to the synthesis of aziridines and ? 2-lactams (respectively), and is suggestive of a generic C-H functionalization platform that could simplify the synthesis of aliphatic secondary amines, a class of small molecules that are particularly important features of many pharmaceutical agents.
A general catalytic β-C-H carbonylation of aliphatic amines to β-lactams
Willcox, Darren,Chappell, Ben G. N.,Hogg, Kirsten F.,Calleja, Jonas,Smalley, Adam P.,Gaunt, Matthew J.
, p. 851 - 857 (2016)
Methods for the synthesis and functionalization of amines are intrinsically important to a variety of chemical applications. We present a general carbon-hydrogen bond activation process that combines readily available aliphatic amines and the feedstock gas carbon monoxide to form synthetically versatile value-added amide products. The operationally straightforward palladium-catalyzed process exploits a distinct reaction pathway, wherein a sterically hindered carboxylate ligand orchestrates an amine attack on a palladium anhydride to transform aliphatic amines into β-lactams. The reaction is successful with a wide range of secondary amines and can be used as a late-stage functionalization tactic to deliver advanced, highly functionalized amine products of utility for pharmaceutical research and other areas.
