d-Fructose-derived β-amino alcohol catalyzed direct asymmetric aldol reaction in the presence of p-nitrophenol

Abstract

D-Fructose derived b-amino alcohols 2 and 3 were used as organocatalysts for direct asymmetric aldol reaction of various aromatic aldehydes with three kinds of cyclic ketones in the presence of different additives as a co-catalyst. The results showed that the combinations of b-amino alcohol 2 and pnitrophenol built up a novel catalytic system. Loading of 20 mol% 2 and 15 mol% p-nitrophenol gave excellent yields (up to 98% with respect to aldehyde) of aldol reaction products with good enantioselectivity (up to 87% ee). Accordingly, a mechanism for the reaction was proposed by 1 H NMR spectrum in this paper. Furthermore, the catalysts can be reused and have the significant catalyst recovery (77-84%).

Catalytic Efficiency of Primary β‐Amino Alcohols and Their Derivatives in Organocatalysis

“…Recently, Fang and co‐workers have also reported the same aldol reactions between various aromatic aldehydes and cyclic ketones catalysed by d ‐fructose‐derived primary β‐amino alcohols 77 and 78 as organocatalysts to afford chiral aldol adducts with excellent yields and moderate to good enantioselectivities (Scheme ). The authors describe a plausible reaction course through enamine bond formation between the amine and the ketone and noncovalent hydrogen bond formation between the free hydroxy group and the aldehyde (Scheme ).…”

Growing Impact of Carbohydrate‐Based Organocatalysts

“…Furthermore, the ring strain (angular strain in the ring) of cyclic ketone also affected the yield and enantioselectivity of the product. Based on results, cyclohexanone exhibited the best activity with higher yields and enantioselectivity in shorter reaction time in comparison to 6 and 5 membered cyclic ketone, possibly because of stability of six membered ring reduces the energy of transition state in the reaction [156] …”

“…The proposed transition state of amino alcohol 81 a catalyzed asymmetric aldol reaction was shown in Figure 28. It is presumed that activation of carbonyl group of aromatic aldehyde takes place via the hydrogen bonding with p ‐nitrophenol and hydroxyl group of the sugar unit of catalyst [156] …”

Synthesis and Applications of Carbohydrate-Based Organocatalysts

“…Other examples of organocatalysed aldol reactions were reported in 2013 by Fang and co-workers [ 199 ]. They exploited for the first time amino alcohols derived from d -fructose, such as 513 and 514 ( Figure 35 ).…”