Organocatalytic Asymmetric Synthesis Of3-Nitro-2H-chromenes&3-Nitro-1,2-dihydroquinolines

Organocatalysis, that is using small organic molecules to catalyse organictransformations, has become a well-established and powerful synthetic tool for theconstruction of chiral compounds. Chiral2H-chromenes and1,2-dihydroquinolinesare important structural motifs frequently found in many natural products andsynthetic molecules with unique biological and pharmacological activities. Moreover,these two classes of compounds can be readily transformed to valuable chiralchromans and1,2,3,4-tetrahydroquinolines, respectively. Therefore, the investigationof organocatalytic asymmetric synthesis of chiral2H-chromenes and1,2-dihydroquin-olines appeared to be of great importance.Starting from amino acids such as trans-4-hydroxy-L-proline, L-phenylalanineand L-proline, organocatalysts I-a, I-b, II, as well as III were synthesized in thisthesis. Then, these catalysts were used to promote the domino oxa-Michael–Henryreaction of salicylaldehyde derivatives with trans-β-nitro olefins, providing chiral3-nitro-2H-chromenes. Of the four organocatalysts, I-a is the most effectiveorganocatalyst in terms of yield and enantioselectivity, wheras MacMillan’simidazolidinone II exhibits almost no catalytic activity. Under the optimizedconditions, the domino oxa-Michael–Henry reaction of a range of salicylaldehydederivatives with trans-β-nitro olefins were examined in the presence of I-a. Fourteenchiral3-nitro-2H-chromenes were obtained in37-99%yields and with up to90%ee.Based on the iminium-deprotonation activation mode, a new strategy has beenestablished for the organocatalytic asymmetric synthesis of chiral3-nitro-1,2-dihydro-quinolines via installation of electron withdrawing sulfonyl groups at the aminofunction of2-aminobenzaldehyde. Electron-withdrawing sulfonyl group in thesulfonamide substrate, increasing the acidity of N–H, is essential for the observedreactivity in domino aza-Michael–Henry reaction with trans-β-nitro olefins, as noreaction was observed when N-Ac, Cbz, Boc or Bn-protected2-aminobenzaldehydewas used.In addition, chiral2-nitro-3H-pyrrolizines were succefully obtained by applyingiminium-deprotonation activation mode to the domino aza-Michael–Henry reaction of2-formylpyrrole derivatives with trans-β-nitro olefins, albeit with poorenantioselectivity.