Direct amino acid-catalyzed cascade biomimetic reductive alkylations: application to the asymmetric synthesis of Hajos-Parrish ketone analogues.
A direct amino acid-catalyzed chemo- and enantioselective process for the double cascade synthesis of highly substituted 2-alkyl-cyclopentane-1,3-diones, 2-alkyl-3-methoxy-cyclopent-2-enones and Hajos-Parrish (H-P) ketone analogs is presented via reductive alkylation chemistry. For the first time, we have developed a single-step alkylation of cyclopentane-1,3-dione with aldehydes/ketones and a Hantzsch ester through an organocatalytic reductive alkylation strategy. A direct combination of amino acid-catalyzed cascade olefination-hydrogenation and cascade Robinson annulations of cyclopentane-1,3-dione, aldehydes/ketones, a Hantzsch ester and methyl vinyl ketone furnished the highly functionalized H-P ketone analogues in good to high yields and with excellent enantioselectivities. Many of the reductive alkylation products have shown direct applications in pharmaceutical chemistry.
Ramachary
Dhevalapally B
DB
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India. ramsc@uohyd.ernet.in
Kishor
Mamillapalli
M
D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D002384:Catalysis; D003517:Cyclopentanes / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction
D000596:Amino Acids; D003517:Cyclopentanes; D007659:Ketones