Iron-Catalyzed Aerobic Dehydrogenative Kinetic Resolution of Cyclic Secondary Amines

Abstract

A nonenzymatic iron-catalyzed dehydrogenative kinetic resolution of cyclic secondary amines using air as an oxidant has been reported. The economical and practical method is applicable to a series of cyclic benzylic amines, including 5,6-dihydrophenanthridines and 1,2-dihydroquinolines, with diverse functional groups at the α position in high yields with excellent enantioselectivities. The direct dehydrogenative kinetic resolution of advanced intermediates of bioactive molecules that are difficult to access using existing catalytic asymmetric synthetic strategy was also demonstrated.

Vanadium(V) Complex-Catalyzed One-Pot Synthesis of Phenanthridines via a Pictet-Spengler-Dehydrogenative Aromatization Sequence

“…The absolute configuration of 5w with catalyst (R a ,S)-6f was determined to be S based on the Flack parameter (0.02(6)). The tetrahydroisoquinoline intermediate 4w readily underwent auto-dehydrogenative aromatization, which implies that the enantioenrichment step may be the carbon-carbon bond-forming step of the Pictet-Spengler reaction, i.e., intermediate A to intermediate B ( Figure 3); we clarified a possibility of kinetic resolution of rac-4b [36] using catalyst (R a ,S)-6f under the reaction conditions as shown in Scheme 2 because isolation of 4w was difficult due to its stability. After 3 h, 70% of 4b was converted to 5b and the optical purity of the recovered 4b was 8% ee.…”

Catalytic Kinetic Resolution and Desymmetrization of Amines

“…In 2019, Liu and co-workers reported a nonenzymatic chiral iron complex (cat-28) catalyzed dehydrogenative KR of cyclic secondary amines with air as an oxidant 54 (Scheme 27). This economical and practical method is applicable to a range of cyclic secondary amines, including 5,6-dihydrophenanthridines (79a-d) and 1,2-dihydroquinolines (79e and f) bearing various α-aryl and alkyl substitutions.…”

Asymmetric Synthesis of Hydroquinolines with α,α‐Disubstitution through Organocatalyzed Kinetic Resolution

“…The Akiyama group developed a delicate method for KR of cyclic secondary amines through asymmetric dehydrogenation with imines enabled by chiral phosphoric acid (CPA) catalysis [13] (Figure 1, b). Recently, the Liu group disclosed KR of α‐substituted 1,2‐dihydroquinolines (DHQs) and 5,6‐dihydrophenanthridines through chiral iron complex catalyzed asymmetric dehydrogenation, in which air was used as the oxidant [14] . However, to the best of our knowledge, the scope of all the aforementioned methods have been limited to KR of cyclic amines with α‐mono‐substitution, and KR of cyclic amines with α,α‐disubstitution through these methods is formidable.…”