Asymmetric Cyanation of α‐Ketiminophosphonates Catalyzed by Cinchona Alkaloids: Enantioselective Synthesis of Tetrasubstituted α‐Aminophosphonic Acid Derivatives from Trisubstituted α‐Aminophosphonates

Abstract

An enantioselective synthesis of tetrasubstituted a-phosphono-a-amino nitriles through asymmetric cyanation of a-ketiminophosphonates catalyzed by Cinchona alkaloids is reported. a-Ket-

α‐Iminophosphonates: Useful Intermediates for Enantioselective Synthesis of α‐Aminophosphonates

“…In 2012, inspired in Steglich's methodology for the synthesis of phosphorylated aldimines 2, [16] a new synthesis of N-Tosyl protected α-aryl ketiminophosphonates 11 through a formal oxidation of α-aminophosphonates was reported. [24] The synthesis was performed through an initial halogenation of the nitrogen atom using trichloroisocyanuric acid (TCCA), followed by the elimination of hydrogen chloride promoted by a polymer-supported base. This represents a useful strategy to access α-ketiminophosphonates using the corresponding α-aryl α-aminophosphonates 10 as starting materials (Scheme 5).…”

“…For instance, the first enantioselective nucleophilic addition to an open‐chain α‐ketiminophosphonate was achieved in 2012 through an enantioselective cyanation reaction of α‐iminophosphonates 53 , using pyruvonitrile and 10 mol% of cinchona alkaloid XVI (Scheme ).…”

Recent Advances in the Catalytic Asymmetric Construction of Phosphorus-Substituted Quaternary Carbon Stereocenters

“…In 2012, the Palacios group reported an efficient method to access chiral quaternary α-amino-α-cyanophosphonates 212 via an asymmetric cyanation of α-ketiminophosphonates. 113 Cinchona alkaloid derived cinchonidine (211) smoothly catalyzed the reaction of pyruvonitrile (210) as the cyanide source and aryl-substituted α-ketiminophosphonates 209 to give α-amino-α-cyanophosphonates 212 in good yields and enantioselectivities (Scheme 62). It should be noted that the dialkyl ester groups of the phosphonate played an important role in the stereochemistry, because replacement of the i Pr group with Me, Et, Bn, or Ph led to a drastic decrease in the enantioselectivity.…”

Asymmetric Synthesis of Quaternary α‐Amino Acids and Their Phosphonate Analogues

“…In 2012, the Palacios group developed a Strecker reaction for the enantioselective synthesis of tetrasubstituted acyano-a-aminophosphonates 244 (Scheme 82). [107] The reaction between a-ketiminophosphonates 243 and methyl cyanoformate was catalyzed by cinchonidine C79 (10 mol %) and afforded 244 in good yields with good to high enantioselectivities. Global hydrolysis of 244 (Ar = Ph) in 10 n HCl provided (S)-a-phosphonophenylglycine (245) in good yield.…”