Abstract
Arjan Viram Odedra, Ph.D., National Tsing Hua University, June 2006. Cobalt and Ruthenium Complexes Mediated/Catalyzed Intramolecular Cyclization of Enynes. Advisor: Professor Rai-Shung Liu Intramolecular cyclizations of enynes mediated/catalyzed by cobalt and ruthenium complexes are described in this dissertation. The thesis is divided into three chapters. First chapter presents cobalt mediated double carbonylative cycloaddition of epoxy alkyne with tethered alkyne. In the presence of Co2(CO)8 and CO, cis-epoxyalkynes bearing a tether olefin undergo a tandem [5 + 1]/[2 + 2 + 1] and/or [5 + 1]/[2 + 2]-cycloaddition depending on substrate and condition. In this novel cycloaddition reaction cobalt stitches together cis-epoxy alkyne, CO and olefin in highly stereocontrolled way to synthesize tricyclic -lactones efficiently in a one-pot operation. The reaction mechanism is proposed to involve a cobalt-coordinated cyclic allene species. This new approach is successfully extended to construct various tricyclic carbo- and heterocyclic frameworks that can tolerate suitable oxygen and nitrogen functionalities. Second chapter deals with ruthenium catalyzed anionic bergman cyclization of unstrained enediynes. TpRu(PPh3)(CH3CN)2PF6 (10 mol%) catalyst effected the nucleophilic addition of water, alcohols, aniline, acetylacetone, and dimethyl malonate to unfunctionalized enediynes under suitable conditions (100 oC, 12-24 h), and gave functionalized benzene products in good yields. In this novel cyclization, nucleophiles very regioselectively attack the internal C1’-alkyne carbon of enediynes to give benzene derivatives as a single regioisomer. Experiments with methoxy substituents exclude the possible involvement of naphthyl cations as reaction intermediates in the cyclization of (o-ethynylphenyl) alkynes. Deuterium-labeling experiments indicate that the catalytically active species is ruthenium-□-alkyne rather than ruthenium-vinylidene species. This hypothesis is further confirmed by the aromatization of o-(2’-iodoethynyl)phenyl alkynes with alcohols. We propose a nucleophilic addition/insertion mechanism for this nucleophilic aromatization based on a series of experiments. Last chapter discusses ruthenium catalyzed cycloisomerization of enenye. TpRuPPh3(CH3CN)2PF6 (10 mol %) catalyzed the cycloisomerization of unactivated cis-3-en-1-ynes and efficiently produces stable cyclopentadiene and related derivatives. TpRuPPh3(CH3CN)2SbF6 catalyzed cycloisomerization of 1-alkyl-2-ethynyl benzene to 1-alkyl-1H-indene in excellent yield whereas TpRuPPh3(CH3CN)2PF6 was inactive. The mechanism of this cyclization is proposed to involve a [1, 5]-sigmatropic hydrogen shift of ruthenium-vinylidene intermediates on the basis of deuterium labeling experiments. TpRuPPh3(CH3CN)2PF6 also catalyzed isomerization of TBS-protected cis-2-en-4-yn-1-ol to afford cyclopentenone derivatives in good yield.