Lanthanide‐Catalyzed Tandem Insertion of Secondary Amines with 2‐Alkynylbenzonitriles: Synthesis of Aminoisoindoles

Abstract

A lanthanide-catalyzed intermolecular hydroamination of 2-alkynylbenzonitriles with secondary amines has been disclosed, providing a streamlined access to a range of aminoisoindoles in moderate to excellent yields. The salient features of this reaction include high bond-formation efficiency, mild reaction conditions, 100 % atomic efficiency and good functional group tolerance. This methodology has also been successfully applied to the construction of other nitrogen-containing compounds, such as 5 H-imidazo[2,1-a]isoindoles and isoquinolines. A plausible mechanism for the formation of aminoisoindoles involving initial N-H activation by a lanthanide complex followed by C≡N insertion into a Ln-N bond to form an amidinate lanthanide intermediate, which undergoes the cyclization is proposed.

Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles with Arylboronic Acids: Synthesis of 2-Arylquinolines

“…Compared to the addition reaction of organometallic reagents such as organolithium or organomagnesium to nitriles, the above-mentioned carbopalladation reagents are highly regarded due to their advantages of stability to air and moisture as well as good functional group tolerance. Inspired by hereinbefore work, as a part of our research program aimed at transition-metal-catalyzed synthesis of N-containing heterocycles with organoboron reagents and nitriles, we envisioned that palladium-catalyzed carbopalladation of 2-aminostyryl nitrile derivatives would afford 2-aminostyryl ketone derivatives easily, which might further prompt an intramolecular nucleophilic attack onto this in situ formed carbonyl group by −NH 2 with the aid of Lewis acid and/or acid medium, providing the desired 2-arylquinoline skeletons (Scheme d). Compared to direct cyclization protocol of 2-aminostyryl ketone derivatives for the construction of 2-arylquinolines, this would be an attractive synthetic strategy in research, since it provides easy and rapid access to large libraries of organic compounds with diverse substitution patterns.…”

Sequential Addition of Amines to Nitrile and Carbon–Carbon Multiple Bond: A Route to 7-Amino-5H-dibenzo[c,e]azepines

“…Pioneering work reported in 2010 by Xie and co-workers showed that titanium amides could catalyze a sequential inter- and intramolecular hydroamination of cyanoalkynes with amines or nitriles with propargylamines, affording the substituted isoindoles, isoquinolines, or imidazoles (Scheme a and b) . Similar transformations were subsequently reported using rare earth catalysts . Demir et al reported that Ph 3 PAuCl and Zn­(ClO 4 ) 2 cooperatively catalyzed tandem hydroamination/cyclization reaction of electron-deficient cyanoalkynes with amines to give 2-aminopyrroles as the main products with a different cyclization pattern (Scheme c) .…”

Rare‐Earth‐Metal‐Catalyzed Synthesis of Azaindolines and Naphthyridines via C−H Cyclization of Functionalized Pyridines

“…To gain some insight into the mechanism of this rare‐earth‐metal‐catalyzed C−H bond activation/cyclization process, a set of control experiments were conducted. First, 1 H NMR monitoring revealed that the addition of Y[N(TMS) 2 ] 3 (10 mol%) to 1 a in toluene‐ d 8 at 100 °C led to the complete liberation of the (Me 3 Si) 2 N ligand (a new peak at 0.08 ppm) from the catalyst and 1 a was cleanly converted into 2 a (Figure ).…”