1,2‐Diamine‐Derived (thio)Phosphoramide Organocatalysts in Asymmetric Michael Additions

Abstract

Phosphoramides and thiophosphoramides were prepared from optically pure C2‐symmetric 1,2‐diamines and were used as chiral organocatalysts in the asymmetric Michael additions of aldehydes and ketones to N‐substituted maleimides. The 1,2‐diphenylethane‐1,2‐diamine derived thiophosphoramide, which could be prepared in good yield in a one‐step procedure, was found to be more active and selective catalyst in the addition of aldehydes to various maleimide derivatives, when compared to sulfonamides having the same backbone. Products resulted in reactions of ketones with maleimides were also obtained in high yields and enantioselectivities. The thiophosphoramide derivative was also efficient in the asymmetric conjugate addition of carbonyl compounds to β‐nitrostyrene and in the reaction of nitromethane with α,β‐unsaturated ketones. Based on results obtained with (thio)phosphoramides in asymmetric additions to maleimides it was suggested that a weaker, more flexible hydrogen‐bonding of the rigid electrophile to the catalyst is responsible for the improved performance of these bifunctional organocatalysts, as compared with sulfonamides.

Recent Advances in Organocatalytic Asymmetric Michael Addition Reactions to α, β‐Unsaturated Nitroolefins

“…Using 20 mol % of catalyst 92, the product 91 was obtained with high ee with a poor yield at 70°C in 144 h. Initially, this reaction was activated through the formation of enamine intermediate by the interaction of catalyst 92 with isobutyraldehyde 1 (Scheme 23). [70] In 2020, Armando Carlone and his co-workers demonstrated an organocatalyzed Michael addition reaction of acetaldehyde dimethyl acetals 93 with several substituted nitroolefins 94 catalyzed by catalyst 96. Herewith, 10 mol % amberlyst-15 was used as a co-catalyst to deprotect the acetals 93.…”

α‐Amino Acids and α,β‐Dipeptides Intercalated into Hydrotalcite: Efficient Catalysts in the Asymmetric Michael Addition Reaction of Aldehydes to N‐Substituted Maleimides

“…Very recently, Szőllősi et al. reported the use of L‐proline adsorbed on the solid surface of diverse inorganic oxides and ion exchanger layered materials, where Laponite RD (synthetic cationic exchanger layered magnesia‐silicate) afforded the best results in the Michael addition of carbonyl compounds to β‐nitrostyrenes using the mixture of solvents chloroform:isopropanol, 9 : 1 [15] . As part of this study, hydrotalcite was evaluated as additive affording excellent conversion (>99 % yield).…”

“…For example, green solvents such as ionic liquids and deep eutectic solvents, [13] or solvent‐free conditions have been used to synthetize chiral succinimides [9d] . Furthermore, both covalently and non‐covalently immobilized organocatalysts, [14,15] represent advantages such as easy recovery and reuse of the heterogenized catalyst. In this regard, Szőllősi et al .…”

Chitosan as a chiral ligand and organocatalyst: preparation conditions–property–catalytic performance relationships

“…Better transformation was reached in water accompanied by low ee (Table 6, entry 1). Acidic additives, which besides solubilizing chitosan in water, may affect the formation of the reaction intermediates, 69 decreased the conversion and had beneficial effect on the ee (entries 2-4). Thus, we carried out further experiments with addition of benzoic acid (BzOH), which afforded only slightly decreased conversion and moderate ee (55%).…”

“…It is known that the Michael addition catalysed by primary amines proceeds through an enamine intermediate. 69 In contrast with the reaction catalysed by the monomer, this nucleophilic moiety will approach preferentially the opposite side of the maleimide in the presence of the polymer chain. A plausible explanation of this inversion is that the polymeric framework allows multiple anchoring of the activated olefin, which may also account for the more efficient activation of the electrophilic reactant, thus, for the faster reaction, compared to D-GlcNH 2 .…”