Syntheses of biologically active natural products using metal-mediated reactions as key reactions

Abstract

This review deals with total syntheses of biologically active natural products by the use of metal-mediated coupling reactions as key steps. First, we explored the coupling reactions mediated by samarium (II) diiodide (SmI2), which is a useful versatile one electron reducing reagent. The SmI2-mediated coupling reactions of N,N-dibenzyl-alpha-bromoamide and N,N-bis(p-methoxyphenyl)-alpha-bromoamide with carbonyl compounds gave the corresponding beta-hydroxyamides, respectively. Then, oxidative treatment of compound 6c with ceric (IV) ammonium nitrate (CAN) gave d,l-myrmicacine (7b). Synthesis of pyrrolizidine alkaloid pyrrolam A (8), which causes damage to fertilized eggs at a low concentration, was accomplished via the SmI2-mediated cyclization between a bromoalkyl and ynamide group. Next, (+/-)-oxerine (15), a monoterpene alkaloid, was synthesized starting from 3-bromopyridine. The synthesis of (+/-)-oxerine (15) was also carried out via the SmI2-mediated intramolecular cyclization of gamma-ethynyl bromide (40). Next, we focused on the palladium-catalyzed oxidation of alcohol and tried to expand it to the intermolecular cyclization. As a result, treatment of hydroxy-enamines and hydroxy-amines with a palladium catalyst gave the corresponding pyrroles and indoles in moderate to good yields. Finally, the syntheses of three pyrrolidine alkaloids were described. The chromium (II) chloride-mediated coupling reactions of (R)- and (S)-Garner aldehydes (56 and 57) with allyl bromides proceeded with moderate stereoselectivity to afford the corresponding homoallyl alcohols, which were converted to (2R, 3S)-2-hydroxymethyl-3-hydroxypyrrolidine (61), (2R, 3R, 4R)-3-hydroxy-4-methylproline (66), and the enantiomer (77) of (-)-bulgecinine (78).