Development of new olefin metathesis reactions via substrate modification: Alkyne and olefin metathesis

학위논문 (박사)-- 서울대학교 대학원 : 화학부 유기화학 전공, 2016. 2. 최태림.Olefin metathesis (OM) reaction is a facile reaction to synthesize various molecules through carbon-carbon double bond rearrangement. With the development of more reactive yet functional group tolerant catalysts, OM proved its usefulness and became one of the most important reaction in modern organic chemistry. Among the various olefins that can subjected to OM, alkynes have special characteristic. As OM only exchanges carbon-carbon double bonds, reaction between alkyne and metal carbene catalyst does not completely cleave carbon-carbon triple bond: instead, new metal 1,3-dienylidene is formed, which can undergo further metathesis reactions, such as enyne metathesis or conjugated polyene synthesis. This thesis will describe about the various application of OM with alkynes, from synthesis of small molecules to high-molecular-weighted conjugated polyenes. Chapter 2 describes synthesis of multicyclic compounds through selective tandem dienyne ring-closing metathesis (RCM) reaction and Diels-Alder reaction. Dienyne RCM reaction is a useful reaction to synthesize fused bicyclic compounds, but due to the lack of catalyst selectivity between olefins with same structures, dienyne RCM reaction tend to produce two different isomers with different ring sizes. Also, product of conventional dienyne RCM reaction was restricted to the bicyclic compounds containing small or medium sized rings only. Thus, conformation of 1,3-diene functional group in bicyclic compound was fixed to s-trans conformation, thus further modification such as Diels-Alder reaction was impossible. By modifying the dienyne substrate to contain long tether to synthesize bicyclic compound comprising small (5-7 membered) and large (14-17 membered) rings, both problems could be solved. As cyclization rate of small ring and catalyst exchange rate between alkenes were significantly faster than that of large ring, single isomer could be synthesized from dienyne RCM reaction. Also, due to the flexible macrocycle chain, 1,3-diene functional group could form s-cis conformation, which could undergo Diels-Alder reaction to synthesize multicyclic compound. Chapter 3 describes tandem ring-opening/ring-closing metathesis (RO/RCM) polymerization of monomers containing cycloalkene and alkyne. Although cycloalkenes with low ring strain and alkynes were not suitable for metathesis polymerization, mixing those two functional groups in one monomer facilitated efficient tandem RO/RCM reaction to perform ultrafast living polymerization. Living characteristic of tandem polymerization could also synthesize block copolymers. Also, 1,3-diene functional groups in the polymer backbone could undergo further modification by cycloadditionr reactions. By changing monomer structures, we found out that monomers with certain combinations of cycloalkene, alkyne, and linker group could undergo efficient polymerization, while monomers with other combinations did not. In order to increase polymerization efficiency, two strategies were proposed. Firstly, monomer structures were modified to increase intramolecular RO/RCM with enhanced Thorpe-Ingold effect, which allowed the synthesis of challenging dendronized polymer. Secondly, reaction concentration was reduced to suppress intermolecular side reactions, which could effectively polymerize monomers without structural modifications. In order to further broaden the monomer scope, monomers containing internal alkynes were also studied, and surprisingly, monomers with internal alkynes tend to undergo non-selective α- and β-addition to form two different polymer units with different ring structures. Further studies revealed that steric and electronic effects of internal alkyne substituents changed polymer unit ratio, polymerization reactivity, and even polymerization kinetics. Thorough mechanism study revealed that the rate-determining step of monomers containing certain internal alkyne was six-membered ring cyclization step via β-addition, whereas that for monomers containing other alkynes was the conventional intermolecular propagation step, as observed in other chain-growth polymerization reactions. Last chapter describes about fast cyclopolymerization of 1,7-octadiyne derivatives. Although cyclopolymerization was effective for the synthesis of conjugated polyenes, cyclopolymerization of 1,7-octadiyne was rarely studied, due to the slow polymerization rate by slow six-membered ring cyclization rate. Although this polymerization rate could be increased by using bulky substituents in side chains, simply increasing substituent bulkiness could not effectively increase polymerization rate. Thus, we proposed two strategies to increase polymerization rate. Firstly, dimethyl substitution was introduced to α-position of side chains. This strategy effectively increased polymerization rate by enhanced Thorpe-Ingold effect, and synthesis of 50-mer polymer could be done within 1 hour, instead of previous 24 hours. However, in order to achieve controlled polymerization, reaction temperature should be decreased and polymerization time was increased to 6 hours. To solve this problem, second strategy was applied: by changing substituent position from 4,4-disubstitution to 4,5-disubstitution, polymerization rate was significantly increased, and even living polymerization with narrow PDI and well-predictable molecular weight was possible within 1 hours, and even challenging synthesis of dendronized polymer could be possible. All those polymers were analyzed by UV-Vis, NMR, and IR spectroscopy to observe polymer backbone structures, such as conjugation length of polymer and cis/trans conformation of polymer backbone.Chapter 1. Olefin metathesis reaction with alkyne 1 Brief history of olefin metathesis with alkyne 3 Thesis research 9 References 10 Chapter 2. Synthesis of fused multicyclic compound through dienyne ring-closing metathesis and Diels-Alder reaction 13 Abstract 15 Background 15 Introduction 18 Results and Discussions 19 Conclusion 35 References 36 Chapter 3. Tandem ring-opening/ring-closing metathesis polymerization 39 Abstract 41 Background 42 Part A. Tandem RO/RCM of monomers containing nitrogen linker group 45 Introduction 45 Results and Discussions 46 Conclusion 61 Part B. Strategies and deeper mechanistic study of monomers with low reactivity 62 Introduction 62 Results and Discussions 62 Conclusion 82 References 83 Chapter 4 Fast diyne cyclopolymerization of 1,7-octadiynes 87 Abstract 89 Backgrounds 89 Part A. Cyclopolymerization of 1,7-octadiynes containing dimethyl substituents in α-position of side chain 93 Introduction 93 Results and Discussions 95 Conclusion 104 Part B. Cyclopolymerization of 4,5-disubstituted 1,7-octadiyne 106 Introduction 106 Results and Discussions 107 Conclusion 120 References 120 Supporting Information 123 국문 초록 135Docto