Asymmetric Hydrocyanation of N‐Phosphinoyl Aldimines with Acetone Cyanohydrin by Cooperative Lewis Acid/Onium Salt/Brønsted Base Catalysis

Abstract

α-Amino acids are of fundamental importance for life. Both natural and artificial α-amino acids also play a crucial role for pharmaceutical purposes. The catalytic asymmetric Strecker reaction still provides one of the most attractive strategies to prepare scalemic α-amino acids. Here we disclose a new concept for Strecker reactions, in which an achiral Brønsted base cooperates with a Lewis acid and an aprotic ammonium salt, which are both arranged in the same chiral catalyst entity. The described method could successfully address various longstanding practical issues of this reaction type. The major practical advantages are that (1) the N-protecting group is readily removable, (2) acetone cyanohydrin is attractive as cyanation reagent in terms of atom economy and cost efficiency, (3) an excess of the cyanation reagent is not necessary, (4) the new method does not require additives and (5) is performed at ambient temperature.

Acceleration by Double Activation Catalysis and its Negation with Rising Temperature in Hydrolysis of Cellobiose with Phthalic and Hydrochloric Acids

“…Such cooperative catalytic mechanisms are particularly widespread in asymmetric organic synthesis. [8][9][10][11][12] DFT provided theoretical activation energy of the double-activated cellobiose hydrolysis (with salicylic acid and a proton) that is close to the value observed experimentally in hydrolysis with salicylic acid alone; [7] however, numerous concurrent pathways may be possible in practice, and experimental E a alone cannot be a conclusive proof of such mechanism. Nonetheless, validity of this theory is important to verify.…”

“…Generally, simultaneous activation of one substrate by two distinct catalysts is known as double activation catalysis (Scheme 1); a closely related phenomenon is synergistic catalysis where each of the two distinct catalysts activates a separate distinct reactant molecule. Such cooperative catalytic mechanisms are particularly widespread in asymmetric organic synthesis [8–12] . DFT provided theoretical activation energy of the double‐activated cellobiose hydrolysis (with salicylic acid and a proton) that is close to the value observed experimentally in hydrolysis with salicylic acid alone; [7] however, numerous concurrent pathways may be possible in practice, and experimental E a alone cannot be a conclusive proof of such mechanism.…”

“…In principle, a closely related type of catalysissynergistic catalysis, in which each of the two catalysts activates a distinct reactant molecule [8] -should also be negatively affected by rising temperature because it involves a reaction between two different reactant-catalyst complexes, and equilibrium concentration of such complexes was explained to be unfavorably affected by heating. Cooperative catalytic mechanisms are particularly widespread in such popular and relevant field of research as asymmetric catalysis, [8][9][10][11][12] where such mechanisms may be responsible for stereoselectivity. [19] Despite the popularity of this catalysis area, influence of temperature on reactions driven by such cooperative catalytic mechanisms remains largely unexplored.…”

Making Chiral Salen Complexes Work with Organocatalysts

“…The cooperative Lewis acid/onium salt/Brønsted base catalysis developed by Peters was also efficiently applied to the enantioselective hydrocyanations of aldimines. 71 This group performed the Strecker reaction by the addition of acetone cyanohydrin (an attractive cyanation agent releasing only acetone as by-product) to phosphinoyl aldimines (as storable and easily deprotected imine precursors). After optimization of the catalytic system, i.e.…”

“…The cooperative Lewis acid/onium salt/Brønsted base catalysis developed by Peters was also efficiently applied to the enantioselective hydrocyanations of aldimines. 71 This group performed the Strecker reaction by the addition of acetone cyanohydrin (an attractive cyanation agent releasing only acetone as byproduct) to phosphinoyl aldimines (as storable and easily deprotected imine precursors). After optimization of the catalytic system, that is, the structure of the ammonium unit linked to the aluminum-complex 28 and the nature of the catalytic base used to liberate a cyanide anion from acetone cyanohydrin, the reaction occurred efficiently with various N-phosphinoyl aldimines to deliver the targeted enantioenriched α-amino acid precursors in good to excellent yields and up to 90% ee (see Scheme 32).…”