Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland-Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation sequence: scope and applications of organocatalytic biomimetic reductions.
A practical and novel organocatalytic chemo- and enantioselective process for the cascade synthesis of highly substituted 2-alkyl-cyclohexane-1,3-diones and Wieland-Miescher (W-M) ketone analogs is presented via reductive alkylation as a key step. First time, we developed the one-step alkylation of dimedone and 1,3-cyclohexanedione with aldehydes and Hantzsch ester through an organocatalytic reductive alkylation strategy. Direct combination of l-proline-catalyzed cascade Knoevenagel/hydrogenation and cascade Robinson annulation of CH acids (dimedone and 1,3-cyclohexanedione), aldehydes, Hantzsch ester, and methyl vinyl ketone furnished the highly functionalized W-M ketone analogues in good to high yields and with excellent enantioselectivities. Many of the reductive alkylation products show a direct application in pharmaceutical chemistry.
Ramachary
Dhevalapally B
DB
School of Chemistry, University of Hyderabad, Central University (PO), Hyderabad 500 046, India. ramsc@uohyd.ernet.in
Kishor
Mamillapalli
M
D000438:Alcohols / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000737:chemistry; D006865:Hydrogenation; D006868:Hydrolysis; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012997:Solvents; D013237:Stereoisomerism
D000438:Alcohols; D000447:Aldehydes; D000475:Alkenes; D000596:Amino Acids; D003510:Cyclohexanes; D007659:Ketones; D012997:Solvents; C506365:Cyclohexane