Asymmetric Conjugate Addition of 3‐Hydroxychromen‐4‐Ones to Electron‐Deficient Olefins Catalyzed by Recyclable C₂‐Symmetric Squaramide

Abstract

The readily scalable asymmetric synthesis of the chiral chromone derivatives functionalized at position 2 via electrophilic enantioselective olefination of the chromone core with nitroolefins and ß,γ‐unsaturated α‐ketoesters in the presence of simple C2‐symmetric tertiary amine‐squaramide catalyst was developed. The reaction products were obtained in 80–99% yield with 89–99% ee in 95% EtOH. The absolute configurations of the synthesized chromone derivatives were unambiguously established by transformation of compound (R)‐3 aa to known methyl (R)‐β‐nitro‐α‐phenylpropionate and by the single crystal XRD analysis of compounds (R,S)‐5 aa and (R,S)‐5 ab. Catalyst V poorly soluble in common organic solvents could be easily separated from the reaction mixture and reused up to 10 catalytic cycles. Catalytic hydrogenation and esterification reactions of the synthesized compounds were carried out to demonstrate synthetic potential of the developed procedure.

Organocatalytic Asymmetric Double Addition of Kojic Acids to 2‐Nitroallylic Carbonates

“…The Pd(0)-catalysis has been recently applied for acylation of weakly nucleophilic 3-hydroxychromen-4-one derivatives. [16] Apparently, the catalyst undergoes the CÀ O oxidative addition to carboxylic acid anhydride thus generating active acyl species. [17] We discovered that, unlike the 7 aa/epi-7 aa mixture, the mixed diacetates 10 aa/epi-10 aa could be readily separated to individual diastereomers by column chromatoghraphy on silica gel (Scheme 4).…”

Recent advances in the synthesis of 4H-chromen-4-ones (2012 − 2021)

“…448 Kovalevsky et al established an efficient and highly enantioselective protocol for the functionalization of 3-hydroxy-4H-chromen-4-ones at C-2, through conjugate addition with nitroolefins promoted by C 2 -symmetric tertiary amine-squaramide catalyst 15, in ethanol 95% at room temperature (Scheme 92). 449 Scheme 90 Scheme 91…”

Enantioselective Catalytic Synthesis of α‐Stereogenic Chromen‐4‐one Amino Derivatives

“…[7] The second approach includes enantioselective addition of chromenones to electron-deficient alkenes catalyzed by bifunctional C 2 -symmetric squaramide (OCat B). [8] In both cases, stereogenic center in the reaction products was linked with three carbon atoms (Scheme 1a,b).…”

“…The first method is based on asymmetric reaction of 3‐hydroxychromene derivatives with α , β ‐ynals via the formation of acylazolium intermediates with NHC ( OCat A ) [7] . The second approach includes enantioselective addition of chromenones to electron‐deficient alkenes catalyzed by bifunctional C 2 ‐symmetric squaramide ( OCat B ) [8] . In both cases, stereogenic center in the reaction products was linked with three carbon atoms (Scheme 1a,b).…”