Construction of the N1–C3 Linkage Stereogenic Centers by Catalytic Asymmetric Amination Reaction of 3-Bromooxindoles with Indolines

Abstract

The catalytic asymmetric amination reaction of 3-bromooxindoles with indolines for the construction of the N1-C3 linkage stereogenic centers has been realized for the first time. Moreover, the racemic substrates (3-substituted indolines) were also applicable under the same chiral conditions. The newly developed method conveniently led to a formal synthesis of (+)-psychotrimine.

Enantioselective Synthesis of 3‐Substituted 3‐Amino‐2‐oxindoles by Amination with Anilines

“…Last but not least, the amination of 3‐substituted 3‐bromooxindoles is a useful strategy to obtain this fascinating skeleton (path vi) with advantages as 3‐substitution compatibility, N1−H free without protecting group, and readily modification to the target derivatives. Using indolines as the nucleophiles and chiral Box‐Ni II complex catalyst, the Wang group realized asymmetric synthesis of N ‐tryptamine‐related 3‐alkyloxindole, a precursor for the total synthesis of (+)‐psychotrimine [12] . However, the amination of 3‐bromo‐3‐benzyl oxindole with anilines rendered the desired products with high yield but moderate enantioselectivity, [13] which might be due to the background reaction and amine‐poisoning of the metal catalysts.…”

“…Using indolines as the nucleophiles and chiral Box-Ni II complex catalyst, the Wang group realized asymmetric synthesis of N-tryptamine-related 3-alkyloxindole, a precursor for the total synthesis of (+)-psychotrimine. [12] However, the amination of 3-bromo-3-benzyl oxindole with anilines rendered the desired products with high yield but moderate enantioselectivity, [13] which might be due to the background reaction and amine-poisoning of the metal catalysts.…”

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

“…Encouraged by these results, the focus was shifted to the development of this aza-Morita–Baylis–Hillman reaction using isatin-derived ketimines [ 51 – 53 ]. This reaction could also lead to the construction of tertiary benzylic amines [ 54 – 57 ] and would help in the development of yet another fundamental reaction with commonly used Michael acceptors and inexpensive catalysts. As mentioned earlier, the application of the MBH adduct has greatly contributed to the success of the MBH reaction, as it necessitated quick access to these adducts for the rapid development of other methodologies.…”

Enantioselective Organocatalytic Mannich Reaction and Fluorination Sequence of Pyrazolones to Isatin‐derived Ketimines

“…3‐Aminooxindole skeleton forms the core structure of biologically active natural products and pharmaceuticals, such as enzyme receptors against vasopressin and potent gastrin/cholecystokinin‐B, chondrogenic and anticancer agents . Because of their pharmaceutical and synthetic importance, a number of efforts have been devoted to the enantioselective construction of 3‐aminooxindole and 4‐substituted pyrazolone derivatives . The development of new approaches for the construction of vicinal quaternary stereogenic carbon centers is an ongoing topics in synthetic organic chemistry .…”