Copper‐Catalyzed Asymmetric Arylation of N‐Heteroaryl Aldimines: Elementary Step of a 1,4‐Insertion

Abstract

Copper complexes of monodentate phosphoramidites efficiently promote asymmetric arylation of N‐azaaryl aldimines with arylboroxines. DFT calculations and experiments support an elementary step of 1,4‐insertion in the reaction pathway, a step in which an aryl‐copper species adds directly across four atoms of C=N−C=N in the N‐azaaryl aldimines.

Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach

“…The copper-catalyzed asymmetric conjugate addition (ACA) of organometallic species is a powerful tool to synthesize new C–C bonds from α,β-unsaturated carbonyl compounds. − After tremendous attention for more than 20 years, the ACA is now arguably one of the most useful asymmetric transformations available to synthetic chemists, and has been used in the synthesis of a variety of natural products. − However, there are still a number of challenges that need to be met to reach its full potential. A lack of robustness in Cu-catalyzed ACAs is well-known, and widely implicated in preventing the approach from enriching mainstream synthetic strategies and methods, , though it should be mentioned that examples of ACAs to give >50 g of product have recently been reported. , Another reason for the underutilization of this method stems from method development being carried out with commonly available substrates, so that seemingly obvious extensions to slightly unusual or more highly decorated reaction partners do not display the desired reactivity patterns. , …”

Rhodium‐Catalysed Asymmetric Arylation of Pyridylimines

“…Catalytic asymmetric arylation of aryl aldimines is an ideal approach to chiral diarylmethylamines, [8] however, construction of pyridine‐incorporating chiral diarylmethylamines by catalytic asymmetric arylation has been rarely studied. To the best of knowledge, only several entries in two reports were disclosed: Lin and Feng realized the rhodium‐catalysed asymmetric addition of two 3‐pyridylboronates to arylimines (Scheme 1‐c, left), [9a] and Zhou achieved the copper‐catalysed asymmetric arylation of two 3‐pyridylimines (Scheme 1‐c, right) [9b] . It is of note that a blocking group next to pyridine nitrogen was necessary in all these cases.…”

Catalytic and Mechanistic Approach to the Metal-Free N-Alkylation of 2-Aminopyridines with Diketones

“…The title compound 24 was synthesized according to general procedure and isolated as a yellow solid (141 mg, 61%) through silica gel flash column chromatography (eluted with 3:1, hexane/ EtOAc). 1 H NMR (500 MHz, CDCl 3 ,): δ 7.87−7.89 (d, J = 5.8 Hz, 1H), 7.24−7.35 (m, 10H), 6.18−6.20 (dd, J = 7.6 Hz, 1H), 5.75− 5.77 (d, J = 7.6 Hz, 2H), 5.25−5.26 (d, J = 5.0 Hz, 1H), 3.66 (s, 3H) ppm.…”