Organocatalytic Enantioselective Construction of Acyclic N,N‐Acetals via Aza‐Addition of Arylamines to Ketimines

Abstract

A chiral phosphoric acid catalyzed enantioselective aza‐addition of arylamines to ketimines has been developed for the construction of chiral acyclic N,N‐acetal motifs. Under the standard conditions, arylamines reacted smoothly with ketimines from isoquinoline‐1,3‐dione to afford a series of acyclic N,N‐acetals in 82–99% yield with 80–96% ee.

An overview of the applications of chiral phosphoric acid organocatalysts in enantioselective additions to CO and CN bonds

“…In the same year, Li and co-workers reported the addition of arylamines 20 to ketimines 195 catalysed by ( S )- H 8 BPA7 (Scheme 91). 243 The reaction affords N , N -acetals 296 in yields up to 99% and enantiomeric excesses ranging from 80 to 96% in most cases. As a limitation, ortho -hindered arylamines such as 1-naphthylamine have adverse effects on the stereocontrol (73%, 12% ee), and the use of alkylamines as nucleophiles produces the racemic product in excellent yield (95%, 0% ee).…”

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

“…In 2021, Li, Dong, Li, and co-workers reported the enantioselective addition of anilines to isoquinoline-1,3(2 H ,4 H )-dione-derived ketimines 169 catalyzed by CPA 161k (Scheme 96A). 153 In 2022, Lin, Duan, and co-workers also reported similar chemistry involving isatin-derived ketimines 21 catalyzed by chiral diamine-type urea 221 (Scheme 96B). 154 Both reactions tolerate a wide range of substrates and delivered high enantioselectivities; however, secondary amines, such as N -alkylaniline, did not react.…”