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Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ 12 ‐Prostaglandin J 3
Author(s) -
Pelšs Andrejs,
Gandhamsetty Narasimhulu,
Smith James R.,
Mailhol Damien,
Silvi Mattia,
Watson Andrew J. A.,
PerezPowell Isabel,
Prévost Sébastien,
Schützenmeister Nina,
Moore Peter R.,
Aggarwal Varinder K.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201802498
Subject(s) - aldol reaction , yield (engineering) , stereoselectivity , cascade reaction , chemistry , prostaglandin , domino , total synthesis , aldol condensation , bicyclic molecule , stereochemistry , catalysis , combinatorial chemistry , organic chemistry , biochemistry , materials science , metallurgy
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 Δ 12 ‐prostaglandin J 3 , a compound with known anti‐leukemic properties.
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