This paper describes a new amino-amide-based transient directing group (TDG). The TDG can exhibit better performance in the Pd-catalyzed arylation of aliphatic aldehydes and ketones. This reaction showed good substrate compatibility and regioselectivity. The results indicated that 3-amino-N-isopropylpropionamide was more beneficial to the β-arylation of aliphatic aldehydes than other TDGs under relatively mild conditions.

The direct arylation of aromatic and aliphatic ketones was carried out via palladium-catalyzed inert CÀH bond functionalization with 2-amino-N-isopropyl-acetamide as a new catalytic transient directing group. The reaction showed excellent functional group compatibility and site selectivity. We demonstrated that aamino amide forming N,N-bidentate coordination with Pd catalyst is more favorable for the b-arylation of ketones than a-amino acid forming N,O-bidentate coordination with Pd catalyst under relatively mild conditions. This elegant approach provides straightforward access to important structural motifs in organic and medicinal chemistry and is demonstrated here in the efficient synthesis of phenanthridinone alkaloids.

The direct Pd-catalyzed β-C–H arylation of aldehydes and ketones was developed by using 2-amino-N,N′-diisopropylsuccinamide as a novel transient directing group (TDG). The TDG showed good versatility in functionalizing unactivated β-C–H bonds of aldehydes and ketones. It was effective not only for aliphatic aldehydes and ketones but also for aromatic aldehydes and ketones. Besides, it was applicable to o-methylbenzaldehydes.