Multifunctional phosphoramide-(S)-prolinamide derivatives as efficient organocatalysts in asymmetric aldol and Michael reactions

Abstract

Knowledge accumulated in the field of organocatalysis led to the design and synthesis of three novel and efficient organocatalysts for the stereoselective aldol and Michael reactions in the presence of water.

On the Synthesis of a Novel Chiral Phosphorodiamidic Acid Containing­ the α-Phenylethyl Moiety: Insights on its Conformation and Reactivity

“…The designed compounds were inspired by the octahydrobenzo-1,3,2-diazaphospholidine-2-oxide moiety A , which has been successfully employed in asymmetric synthesis. 16a b In particular, the bicyclic core of A adopts an anchored conformation as a consequence of the conformationally fixed chair cyclohexane ring that orients the alkyl groups at nitrogen atoms in a trans -diequatorial relationship 16c (Figure 1 ). Furthermore, operation of allylic A 1,3 strain in the α-phenylethyl fragments 17 was anticipated to afford a C 2 -symmetric, helix-type conformation around the phosphoryl group (Figure 1 ).…”

Synthesis and Evaluation of N-Diaminophosphoryl Aminothioureas as Bifunctional Catalysts for Vinylogous Aldol Reactions of Isatins and 2(3H)-Furanones

“…It should be noted that, compared to the more conventional N -aryl aminothioureas, the corresponding N -diaminophosphoryl thioureas are far less explored as organocatalysts and only two studies with such thioureas are reported. 15 Moreover, these studies have only examined enamine-forming versions of the catalysts and there are opportunities for noncovalent catalysis and reaction development with N -diaminophosphoryl aminothioureas containing a basic functionality (e.g., a tertiary amine). We anticipated that enantiomerically enriched, diamine-derived, bifunctional catalysts of this type would offer stereocontrol of the vinylogous aldol reaction.…”

“…We anticipated activation of the isatin by hydrogen-bonding with the thiourea and simultaneous activation of the γ-butenolide by deprotonation with the tertiary amine. It should be noted that, compared to the more conventional N -aryl aminothioureas, the corresponding N -diaminophosphoryl thioureas are far less explored as organocatalysts and only two studies with such thioureas are reported . Moreover, these studies have only examined enamine-forming versions of the catalysts and there are opportunities for noncovalent catalysis and reaction development with N -diaminophosphoryl aminothioureas containing a basic functionality (e.g., a tertiary amine).…”

New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

“…In this context, several representative organocatalysts present two or more functional groups that act in cooperative or bifunctional strategies [12][13][14][15][16][17][18]. Several research groups have used natural and unnatural amino acids and peptides [19][20][21][22][23][24][25][26][27][28][29][30][31], chiral ureas and thioureas [32][33][34][35][36][37][38][39][40], and chiral amides [41][42][43][44][45] as building blocks or templates in organocatalyst design.…”