Towards organo-click chemistry: development of organocatalytic multicomponent reactions through combinations of aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen cycloaddition reactions.
Here we report on our studies on combinations of amino acids and copper(I) for catalyzing multicomponent reactions (MCRs). We aimed to prepare both diene and dienophiles simultaneously, under very mild and environmentally friendly conditions, thus giving the constituents for a stereocontrolled Diels-Alder reaction, which in turn yields compounds 4 to 8. A diversity-oriented synthesis of polysubstituted spirotriones 4 to 6 were assembled from simple substrates like 1-(triphenylphosphanylidene)-propan-2-one, two aldehydes, and cyclic-1,3-diketones through Wittig/Knoevenagel/Diels-Alder and aldol/Knoevenagel/Diels-Alder reaction sequences in one pot under stereospecific organocatalysis. Chemical diversity libraries of polysubstituted spirotrione-1,2,3-traizoles 8 were assembled from simple substrates by means of Wittig/Knoevenagel/Diels-Alder/Huisgen cycloaddition reaction sequences in one pot under stereospecific organo/Cu(I) catalysis. Functionalized dispirolactones such as 6 are biologically active antioxidants and radical scavengers, and spirotrione-1,2,3-traizoles 8 have found wide applications in chemistry, biology, and materials science. Experimentally simple and environmentally friendly, organocatalytic, asymmetric four-component Diels-Alder (AFCDA) reactions of 1-(triphenylphosphanylidene)- propan-2-one, two different aldehydes, and cyclic-1,3-diketones produced diastereospecific and highly enantioselective substituted spirotriones 4 by means of a Wittig/Knoevenagel/Diels-Alder reaction sequence in one pot. Additionally we have developed an organocatalytic, asymmetric three-component Michael (ATCM) reaction of 1-(triphenylphosphanylidene)-propan-2-one, aldehyde, and cyclic-1,3-diketones that produced Michael adducts 15, 16 through a Wittig/Michael reaction sequence in a highly enantioselective one-pot process.
Ramachary
Dhevalapally B
DB
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Barbas
Carlos F
CF
D000596:Amino Acids / Q000737:chemistry; D000975:Antioxidants / Q000138:chemical synthesis; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D016166:Free Radical Scavengers / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis
D000596:Amino Acids; D000975:Antioxidants; D016166:Free Radical Scavengers; D006571:Heterocyclic Compounds; D011083:Polycyclic Compounds; D011759:Pyrrolidines; D012997:Solvents; D013141:Spiro Compounds; D014230:Triazoles; C042514:cuprous ion; D003300:Copper; C032519:pyrrolidine