Enantioselective copper‐aminopyridine‐catalyzed aza‐Henry reaction with chelating N‐(2‐pyridyl)sulfonyl imines

Abstract

This article describes a copper-catalyzed aza-Henry reaction. Copper complexes of camphor-derived aminopyridines catalyze the addition of nitromethane to N-(2-pyridyl)sulfonyl aldimines to give the corresponding β-nitrosulfonamides with good yields and variable enantiomeric excesses (up to 83%). An example of transformation of these compounds into N-(2-pyridyl)sulfonyl-α-amino acids and deprotection of the sulfonamide with Mg-MeOH is provided.

Concise asymmetric synthesis of Linezolid through catalyzed Henry reaction

“…13b-14 Among these, the camphor-derived Cu(II)-amino(imino) pyridine complexes have attracted growing attention due to their good-to-high enantioselectivity combined with the advantage of using a cheap ligand available in both enantiomeric forms. [15][16][17][18][19] At rst, we looked at the obtainment of the aldehyde 3 as substrate for the asymmetric Henry reaction (Scheme 1).…”

Nitro-Mannich Reaction

“…In 2012, the group of Blay and Pedro reported the enantioselective Cu-catalyzed nitro-Mannich reactions of N-(2-pyridyl)sulfonyl imines 117 with nitromethane (Scheme 65). 117 magnesium in MeOH−THF provided a good yield for this transformation.…”

“…In 2012, the group of Blay and Pedro reported the enantioselective Cu-catalyzed nitro-Mannich reactions of N -(2-pyridyl)sulfonyl imines 117 with nitromethane (Scheme ) . They used chiral amino-pyridine ligand 118 in combination with Cu(OTf) 2 and DIPEA to form the β-nitroamine products in moderate to good yields and enantioselectivities.…”

An un-forgotten classic: the nitro-Mannich reaction between nitrones and silyl nitronates catalysed by B(C6F5)3

“…A direct approach for the nitro-Mannich reaction, that is, making the nitronate in situ, would be more appealing, yet the only reports of this used an excess of nitro alkane and it was restricted to specically designed imines. [24][25][26][27][28] A turning point occurred in 2019, when Behr et al showed the possibility to use nitrones as imine surrogates, however, the substrate scope was limited to short chain nitro alkanes and required excess base, which in turn limited the functional group tolerability (Scheme 1b). 29 In addition, a large excess of the nitro nucleophile was required, as the authorsobserved that the process was reversible and following formation of the rst nitro-Mannich product, a retro-nitro-Mannich addition occured, redelivering the starting material.…”