ABSTRACT
Re-investigation of the l-proline catalyzed double aldol cascade dimerization of succinaldehyde for the synthesis of a key bicyclic enal intermediate, pertinent in the field of stereoselective prostaglandin synthesis, is reported. The yield of this process has been more than doubled, from 14 % to a 29 % isolated yield on a multi-gram scale (32 % NMR yield), through conducting a detailed study of the reaction solvent, temperature, and concentration, as well as a catalyst screen. The synthetic utility of this enal intermediate has been further demonstrated through the total synthesis of Δ12 -prostaglandin J3 , a compound with known anti-leukemic properties.
Subject(s)
Aldehydes/chemistry , Fatty Acids, Omega-3/chemical synthesis , Proline/metabolism , Prostaglandins/chemical synthesis , Catalysis , Fatty Acids, Omega-3/chemistry , Molecular Structure , Proline/chemistry , Prostaglandins/chemistryABSTRACT
The asymmetric unit of the title compound, C10H14N2O3, contains two independent mol-ecules with similar conformations. In the both mol-ecules, the cyclo-hexene rings adopt the same envelope conformation with the flap C atoms lying 0.658â (3) and 0.668â (3)â Å from the mean planes formed by the remaining atoms. In the crystal, adjacent mol-ecules are connected via N-Hâ¯O hydrogen bonds and weak C-Hâ¯O inter-actions, forming supra-molecular layers parallel to (-101).
ABSTRACT
Highly chemoselective conjugate reduction of chiral alpha,beta-unsaturated amino ketones has been developed by using triisopropyl phosphite ligated copper hydride complex. The highlights of the method are wide substrate compatibility and exceptional chemoselectivity.