Organocatalytic Enantioselective Henry Reactions

Abstract

A large number of interesting organocatalytic enantioselective protocols have been explored and successfully applied in the last decade. Among them, the Henry (nitroaldol) reaction represents a powerful carbon-carbon bond-forming procedure for the preparation of valuable synthetic intermediates, such as enantioenriched nitro alcohols, which can be further transformed in a number of important nitrogen and oxygen-containing compounds. This area of research is still in expansion and a more complex version of this useful process has recently emerged, the domino Michael/Henry protocol, affording highly functionalized cycles with multiple stereogenic centers.

Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

“…The most common approach to compounds 1 is represented by the enantioselective Henry (nitroaldol) reaction between aldehydes and nitromethane, which is catalysed by metal complexes or organocatalysts [1,[6][7][8][9][10][11][12][13][14][15][16].…”

Synthesis of N,O-Type Inherently Chiral Calix[4]arenes Substituted on the Lower Rim and their Organocatalysis Properties

“…[9][10][11] With the optimized solvents in hand, the effect of temperature on enantioselectivity in the Henry reaction is also studied in a mixed protic solvent (EtOH/H 2 O, 3:1, v/v). The results from the different temperatures (Table 1) showed the enantioselectivity can not be further improved by lowering the temperature at the accompanying expense of increasing the reaction time.…”

“…The resulting nitro alcohol (nitroaldol) products can be transformed into a number of nitrogen and oxygen-containing derivatives such as 1,2-amino alcohols, amino sugars, nitro ketones, nitro alkenes, ketones, and other important compounds. [9][10][11][12][13][14] It was reported that chiral N,O-type cupreidine derivatives can perform outstanding catalytical activities for Henry reaction. Mechanistic studies on their catalytic behaviors indicated they serve as acid-base bifunctional organocatalysts through H-bond interactions with the acceptor and donor components of the reactions through the quinuclidine nitrogen and the aromatic hydroxyl, respectively.…”

Organocatalysis in Total Synthesis

“…In both strategies, ketones, as less explored substrates in organocatalytic Henry reaction [103], were used allowing the achievement of the required chiral quaternary centers with excellent enantioselectivities.…”