Asymmetric aza‐Henry reaction of N‐tosyl imine

Abstract

An efficient stereoselective aza-Henry reaction of N-tosyl imine, catalyzed by the coordination of diethylzinc with a chiral semi-aza-crown ligand, with moderate to high ee (up to 83%) is reported.

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

“…The amount of 4 Å MS was also adjusted, so when the reaction was carried out with 50 mg MS per mmol of imine, an appreciable increase in enantioselectivity was observed with respect to the reaction in the presence of 100 mg MS per mmol of imine (entry 1 versus entry 4). Although the use of MS as an additive in several enantioselective reactions involving nitrocompounds has been shown to have a beneficial effect on the yield and stereoselectivity, the mechanism of this effect is not clear. It has been suggested that, further to act as scavenger for water and proton contaminants that may have a deleterious effect, MS could facilitate the enolization of nitromethane .…”

“…Most significantly, up to two new stereogenic centers can be formed, both attached to two different nitrogen functional groups. As a result, much attention has been paid to the catalytic asymmetric version of this reaction over the past several years by either using metal‐based procedures or organocatalysis . One of the difficulties that arises when carrying out nucleophilic addition reactions to imines is their lower electrophilicity compared with the carbonyl group.…”

“…N ‐phosphinoyl imines have been seldom used because of their poor stability and relatively low reactivity, although the phosphinoyl moiety can be easily removed by acidic hydrolysis. Similarly, there are few reports on the enantioselective aza‐Henry reaction of N ‐sulfonyl protected imines, which are usually bench‐stable solids and can be easily prepared. A possible explanation for this is the difficult deprotection of the N ‐tosyl amines resulting from the nucleophilic addition to the C═N bond.…”

Lanthanide Amide‐catalyzed Aza‐Henry Reaction of N‐Tosyl Imines with Nitroalkanes

“…1 For example, many bifunctional thiourea catalysts, 2 Brønsted-acids, 3a and Na 2 CO 3 3b were reported to be efficient for the aza-Henry reaction. Despite the considerable advances made in this field so far reported, the metal catalysts are restricted, with almost no exception, to the alkoxyl metal compounds, such as Ln(O i Pr) 3 , 4 Ln(OTf) 3 , 4 KOR (R＝ t Bu, i Pr), 5 the Zn alkyoxyl compounds, 6a N,N'-dioxide-Cu(I) complex, 6b or various heterobimetallic complexes using BINOL derivatives as ligands in asymmetric synthesis. 7 Until now, studies on the pure lanthanide amido compounds as catalysts for the aza-Henry reaction remain unexplored.…”

“…22,23 However the studies on the aza-Henry reaction of N-tosyl imines with nitroalkanes are limited. 4,5,24 Herein, we wish to report the aza-Henry reaction of sulfonylimines with nitroalkanes catalyzed by the heterobimetallic lanthanide amide [(Me 3 Si) 2 N] 3 Ln(µ-Cl)Li(THF) 3 .…”