Chiral Brønsted acid-catalyzed hydrophosphonylation of imines—DFT study on the effect of substituents of phosphoric acid

Switching the N‐Alkylation of Arylamines with Benzyl Alcohols to Imine Formation Enables the One‐Pot Synthesis of Enantioenriched α‐N‐Alkylaminophosphonates

“…With the knowledge that allylic alcohols have been successfully applied in iron‐catalyzed hydrogen borrowing N ‐alkylation[14e] and cascade processes and that imines derived from cinnamaldehyde are well‐suited for the enantioselective hydrophosphonylation with chiral phosphoric acids, we decided to subject allylic alcohols to our N ‐alkylation and imine formation conditions (Table ). The reaction of cinnamyl alcohol and crotyl alcohol with either aniline or p ‐anisidine gave mixtures of 4 possible amine and imine products with or without α,β‐unsaturation.…”

“…With this in mind we decided to develop a homogeneous system to synthesize enantioenriched α‐aminophosphonates. As Beller and co‐workers could combine the iron‐based Knölker's complex 1c with chiral phosphoric acids 2 for hydrogenations and phosphoric acids are common organocatalysts for hydrophosphonylations,[9b], we chose to combine similar systems for the exploration of the enantioselective one‐pot condensation of anilines, alcohols and phosphites. In the course of our investigations we found that it is possible to control the selectivity of the N ‐alkylation of aniline promoted by Knölker's complex 1b and 1c by varying the reaction conditions (Scheme ) .…”

[1,1′-Binaphthalene]-2,2′-diol, 3,3′-Bis[3,5-bis(trifluoromethyl)phenyl]-, (1R)-

“…A DFT study suggests that the steric bulk of the bis(3,5-trifluoromethyl)phenyl groups can be used to explain the higher selectivity observed with phosphate 3 compared with other phosphates with less sterically demanding groups. 13 OH OH Ar Ar Ar = 3,5-(CF 3 4 and a cinchona alkaloid such as cinchonidine to generate a bifunctional catalyst that has both a Lewis acidic and a Lewis basic site (eq 10). 14 This in situ generated catalyst is useful for the hydrophosphonylation of aliphatic aldehydes (eq 11).…”

Enantioselective Synthesis of Amines by Chiral Brønsted Acid Catalysts

“…The use of sterically demanding dialkyl phosphites and aldimines derived from cinnamaldehyde derivatives is essential to achieve high enantioselectivities. The same research group and Yamanaka and coworkers conducted DFT computational analysis of hydrophosphonylation [109]. The chiral phosphoric acid plays a significant role in the activation of both imine and phosphite based on its dual functional catalysis.…”