Towards the rational design of ylide-substituted phosphines for gold(i)-catalysis: from inactive to ppm-level catalysis

Abstract

The implementation of gold catalysis into large-scale processes suffers from the fact that most reactions still require high catalyst loadings to achieve efficient catalysis thus making upscaling impractical. Here, we report systematic studies on the impact of the substituent in the backbone of ylide-substituted phosphines (YPhos) on the catalytic activity in the hydroamination of alkynes, which allowed us to increase the catalyst performance by orders of magnitude. While electronic changes of the ligand properties by introduction of aryl groups with electron-withdrawing or electron-donating groups had surprisingly little impact on the activity of the gold complexes, the use of bulky aryl groups with ortho-substituents led to a remarkable boost in the catalyst activity. However, this catalyst improvement is not a result of an increased steric demand of the ligand towards the metal center, but due to steric protection of the reactive ylidic carbon centre in the ligand backbone. The gold complex of the thus designed mesityl-substituted YPhos ligand Y_MesPCy₂, which is readily accessible in one step from a simple phosphonium salt, exhibited a high catalyst stability and allowed for turnover numbers up to 20 000 in the hydroamination of a series of different alkynes and amines. Furthermore, the catalyst was also active in more challenging reactions including enyne cyclisation and the formation of 1,2-dihydroquinolines.