An Asymmetric Nitro-Mannich Reaction Applicable to Alkyl, Aryl, and Heterocyclic Imines

Abstract

[reaction: see text] A protocol for the enantioselective nitro-Mannich coupling between alkyl, aryl, and heterocyclic p-methoxybenzylimines and trimethylsilylnitropropanate catalyzed by a chiral tBu-BOX Cu(II) catalyst is described. It uses the lowest reported loading of commercially available metal catalyst and chiral ligand, and gives the highest yields and selectivities for a broad substrate range including nonaromatic aldimines. The resultant beta-nitroamines are obtained in 70-94% enantiomeric excess in good yield and can be readily reduced to synthetically useful 1,2-diamines.

Phase‐Transfer‐Catalyzed Asymmetric Aza‐Henry Reaction Using N‐Carbamoyl Imines Generated In Situ from α‐Amido Sulfones

“…Despite the remarkable results in terms of enantioselectivity and catalytic efficiency, all methods show a considerable limitation in the variability of the imine partner because preformed imines are employed. We felt that our approach could significantly extend the scope of the reaction, besides providing a new and convenient protocol for this asymmetric transformation 16…”

Enantioselective Aza‐Henry Reactions Assisted by ZnII and N‐Methylephedrine

“…5 In this context, Shibasaki and co‐workers6 described the use of binaphthoxide (binol)‐based heterobimetallic complexes of ytterbium and aluminum as catalysts of the reaction of nitro compounds with N ‐phosphinoyl imines derived from aromatic aldehydes, while Jørgensen and co‐workers7 used copper bis(oxazoline) complexes to catalyze the reaction of silyl nitronates with α‐imino esters. These methods usually require a high catalyst loading (20 mol %), and the substrate scope is limited with regards to one or both of the reaction partners 8. Three alternative organocatalytic aza‐Henry reactions using unmodified nitro compounds have also appeared 9.…”

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

“…These heterocycles could be derived from a common α-keto acid derivative 5 and either diamine 6 or 7 , that could in turn be prepared from β-nitroamine 8 or 9 . Each of the β-nitroamines could be prepared enantioselectively by using our previously reported methodology [28,43,45] and would allow elucidation of the absolute stereochemistry of piperazirum ( 2 ).…”