The use of hydroamination in the attempted synthesis of ant alkaloid 223H (xenovenine).

Abstract

The ability to construct C-N bonds is of great importance to organic chemists as exemplified by the vast number of natural products, pharmaceutical agents and fine chemicals that contain such linkages. An atom efficient C-N bond forming reaction namely hydroamination has attracted much interest to date due to its ability in forming amine, imine and enamine functionality. The scope of this project involved the attempted synthesis of a biologically active and nitrogen containing pyrrolizidine alkaloid isolated from cryptic thief ants and poison dart frogs namely 223H (xenovenine). The method of hydroamination was utilized as the pivotal ring forming step and was established as being a valuable synthetic tool towards the construction of 223H (xenovenine). The stereoselective synthesis resulted in the successful formation of ethyl (3R)-5-heptyl-3-methyl-2,3-dihydro-lH-pyrrolizine-7-carboxylate 74, a novel, and structurally analogous precursor to 223H (xenovenine) over 10 synthetic steps from (S)-pyroglutamic acid. The following research also resulted in the synthesis of two other novel compounds namely ethyl 3-[(2R)-2-methyl-5-thioxotetrahydro-lH-pyrrol-l-yl]propanoate 86 and ethyl 3-{(5R)-2-[(E)-2-ethoxy-2-oxoethylidene]-5-methyltetrahydro-lH-pyrrol-l-yl}propanoate 87. A catalytic hydroamination study on the conversion of C-propargyl vinylogous amides into pyrroles demonstrated that transition metal salts of groups 11 and 12 serve as effective hydroamination catalysts. The oxide, acetate, chloride and nitrate derivatives of group 11 and 12 metals namely Cu(II), Ag(I), Zn(II), Cd(II) and Hg(II) were employed as potential hydroamination catalysts in the oxidation states provided. The Zn(II) catalyst series with the exception ZnO provided the greatest hydroamination yields under mild reaction conditions owing to their high Lewis acidities however the Ag(I) and Hg(II) catalyst series also provided excellent yields of product under more forcing reaction conditions.