Cinchona based squaramide catalysed enantioselective Michael addition of α-nitrophosphonates to aryl acrylates: enantioselective synthesis of quaternary α-aminophosphonates

Abstract

Abstract-Several cinchona based squaramide catalysts were applied in asymmetric Michael addition of α-nitroethylphosphonates to acrylic acid aryl esters, resulting in high yield and enantioselectivity. The absolute configuration of one of the quaternary α-nitrophosphonate adducts was deduced from its experimental and calculated CD spectra. The adducts were reduced to their cyclic aminophosphonates by catalytic hydrogenation.

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

“…The use of 5 mol% quinidine-derived bifunctional squaramide 45c as the catalyst effectively mediated this reaction affording products 138 in 82-93% yields with 40-96% ee (Scheme 41). 82 Generally, the reaction of acrylates bearing electron-donating groups gave higher ees than that of acrylates possessing electron-withdrawing groups. Selective reduction of the nitro group of 138 (R = Et, Ar = Ph) followed by aminolysis of the ester group produced 5-oxopyrrolidinylphosphonate 139 in 51% yield and with 97% ee.…”

Asymmetric Synthesis of Tetrasubstituted α-Aminophosphonic Acid Derivatives

“…Following the same line, in 2013, Jászay and colleagues reported the addition of α-nitrophosphonates 154 to aryl acrylates 155 using also an squaramide organocatalyst VIII ( Scheme 29 ) [ 64 ]. Even though some bulky phosphonates were tested in the reaction with phenyl acrylate, the use of iso -propyl and butyl phosphonates does not result in a further improvement on the reaction yield or enantiocontrol (82–85%, 52–64% ee) and the best enantiomeric excesses are obtained with ethyl phosphonates (93%, 76% ee).…”

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

“…[112] Recently, Jaszay et al described the Michael addition of nitrophosphonates 252 to aryl acrylates 264 in the presence of 5 mol % quinidine-squaramide C83 to afford tetrasubstituted g-nitrophosphonyl carboxylates 255 in high yields, albeit in low to good enantioselectivities (Scheme 88). [113] Furthermore, 5-oxopyrrolidinylphosphonate 256 was obtained in good yield by selective reduction of the nitro group in 255 using Pd/C-H 2 .…”