Study of Intramolecular Cyclization of Organic etero-Containing Enynes Catalyzed by Ruthenium Metal Complexes

在本篇論文中，我們致力於研究半三明治釕金屬錯合物與含異原子的不飽和有機化合物之間的反應並探討其中新穎有趣的化學。文中製備了一系列含胺基、氧基及吡啶官能基的釕金屬烯炔基錯合物與亞乙烯基錯合物。利用釕金屬催化含氮原子的有機1,7-烯炔化合物，經由形成中間體釕亞乙烯基 (4a、4b、4b’ 和 4c’) 後，進行分子內環化反應而得到產物吲哚。亞乙烯基錯合物 4b’進行5-endo-dig環化，接著進行 [3,3]-sigmatropic骨架重排而形成錯合物 [[Ru]{=C(C14H19N)}][PF6] 7b’，進一步在含氯的溶劑中，會進行1,2-氫轉移得到吲哚化合物，並完成此一催化循環。我們在溫和條件下，可直接合成出具多烯取代的吲哚並擁有很好的立體選擇性，只會得到 (SR/RS)構型的產物而不會有另一可能異構物(SS/RR)的產生。當生成錯合物[Cp(PPh3)2Ru=C=CH(Ph)N(CH2CHCMe2)2][PF6] (4c) 時，因為立體障礙而無法生成環化產物，而錯合物[[Ru]=C=CH(Ph)NHCOCH3][BF4] (10) 則是會受到電子效應的影響，無法生成環化產物。一步將含氮的1,7-烯炔化合物，延伸至同樣在苯五號位置上，也具有氮原子的吡啶基炔丙醇化合物，並將其與釕金屬Cp(PPh3)2RuCl在甲醇與四氫呋喃共溶劑中進行反應，可得到一個環化的釕金屬吲哚嗪酮基錯合物 [[Ru]{–C(C7H5ON)}][PF6] (13)。然而，當使用二氯甲烷為反應溶劑時，有趣的是我們會得到三個新產的物 14、15以及16，分別以 2.4 : 1 : 1.6 的比例存在。 [CpPPh3Ruη²-HC≡CC(=O)(C5H4N)][PF6] (14)是一個同時與氮原子及三鍵所配位並藉由一碳氮螯合配位體所連接的錯合物，其中所發生的氧化反應是經由釕金屬醇鹽進行氫負離子轉移，形成釕氫化物及吡啶酮基。15 是個具有三苯基磷加成與碳氮螯合配位體C(H)=C(PPh3)C(=O)(C5H4N) 的六員金屬含氮雜環錯合物；而錯合物 16 則是由配位體C(=CH(PPh3))C(=O)(C5H4N) 結構所構成的五員金屬含氮雜環產物。錯合物 16 和5 分別是親核性的三苯基磷加成在錯合物 14 中配位在金屬上炔基的 Ca 或 Cb 碳位置上所得到的產物。另外，將 12上的羥基以TBS保護得到 17並進一步與 [Ru]Cl在二氯甲烷中進行反應，同樣會得到三苯基磷加成的類似產物 18 和 19。們又製備了一系列的含氧原子的釕炔基錯合物及釕亞乙烯基錯合物[Ru]=C=CH(Ph)OCH2CHCR2][PF6] ([Ru] = CpRuL2; 23a, L = PPh3, R = H; 23b, L =PPh3, R = CH3; 23a’, L = 1/2 dppe, R = H; 23b’, L = 1/2 dppe, R = CH3)。在酸性環境下，錯合物 23a 會失去丙烯基轉變成含氧釕碳烯環錯合物 24；然而，在相同條件下 23a’ 卻不會。對錯合物 Cp(PPh3)2RuC≡CR (28, R = Me; 28’, R = Ph) 進行烷化反應可生成亞乙烯基錯合物 [[Ru]=C=C(R)CH2COOR’][PF6] (29)，並進一步以 n-Bu4NOH去質子化得到釕呋喃錯合物 31a (R = Me, R’= Et) 和 31b (R = Me, R’=CH2CF3)。In this thesis, we investigated versatile reactivities of half-sandwiched ruthenium complexes with hetero-atom containing organic compounds. A series of ruthenium vinylidene and acetylide complexes containing amine, aniline, oxygen, and pyridyl groups have prepared. We studied the intramolecular cyclization of organic 1,7-enynes containing heteroatom catalyzed by ruthenium to form indole products via vinylidene intemediates [[Ru]=C=CH(Ph)N(CH2CHCR1R2)2][PF6] ([Ru] = CpRuL2; 4a, L = PPh3, R1 = R2 = H; 4b, L = PPh3, R1 = CH3, R2 = H; 4b’, L = 1/2 dppe, R1 = CH3, R2 = H; 8c’, L = 1/2 dppe, R1 = R2 = CH3). Complex 4b’ undergoes a 5-endo-dig cyclization followed by a [3,3]-sigmatropic rearrangement to give complex [[Ru]{=C(C14H19N)}][PF6] 7b’. Further reaction in chlorinated solvent resulting in formation of the indole product 6b via a 1,2-hydrogen migration furnishes a catalytic cycle. This cyclization reaction provides a direct approach to substituted indole compound under mild condition and gives good diasetereoselectivity. Only (SR/RS) form products are obtained without observing the other probable (SS/RR) isomers. Complexes 4a and 4c’ can undergo a resembling transformation to form indoles 6a and 6c, respectively. The cyclization is also influenced by the steric effect and electronic effect in the cases of [Cp(PPh3)2Ru=C=CH(Ph)N- (CH2CHCMe2)2][PF6] (4c) and [[Ru]=C=CH(Ph)NHCOCH3][BF4] (10) where no cyclization product is formed. urther extention of the N-containing 1,7-enynes gives a propargylic alcohol pyridine 12, where the N-atom is at the C5-position on the phenyl ring. Reaction of Cp(PPh3)2RuCl with 12 affords a cyclic indolizinone complex [[Ru]{–C(C7H5ON)}][PF6] (13) in a mixture of methanol and THF. Dramatically, using CH2Cl2 as a solvent, treatment of 12 with [Ru]Cl in the presence of KPF6 yields three new products, 14, 15 and 16, in a ratio of 2.4 : 1 : 1.6. Complex [CpPPh3Ruη²-HC≡CC(=O)(C5H4N)][PF6] (14)s an alkynyl-N-coordinating intermediate with chelating C,N ligand. The oxidation via b-hydride transfer from ruthenium-alkoxide generates ruthenium-hydride and the ketone pyridine ligand. Complex 15 is a six-membered aza-metallacyclic phosphine-additionompound with one coordinating PPh3 and one N,C-chelating C(H)=C(PPh3)C(=O)(C5H4N) ligand. Complex 16 is a five-membered azametallacyclic cationic complex with one coordinating PPh3 and one N,C-chelating C(=CH(PPh3))C(=O)(C5H4N) ligand. The formation of 16 and 15 are from the nucleophilic addition of PPh3 to Ca and Cb of coordinated alkyne of complex 14, respectively. Alternatively, the hydroxyl group of 12 is protected by a TBS group to yield 17 and further reaction of 17 with [Ru]Cl in the presence of KPF6 in CH2Cl2 also leads to formation a mixture of phosphine-addition products 18 and 19 in a ratio of 1:4. series of oxygen-containing acetylide and vinylidene complexes [[Ru]=C=CH(Ph)OCH2CHCR2][PF6] ([Ru] = CpRuL2; 23a, L = PPh3, R = H; 23b, L =PPh3, R = CH3; 23a’, L = 1/2 dppe, R = H; 23b’, L = 1/2 dppe, R = CH3) are prepared.omplex 23a transforms to an oxycarbene complex 24 by removing the allyl group under acidic condition, but, the vinylidene complex 23a’ would not give the cyclicarbene complex under the same reaction condition. Other vinylidene complexes [[Ru]=C=C(R)CH2COOR’][PF6] (29) are synthesis by alkylation reactions of alkyl halides with two acetylide complexes Cp(PPh3)2RuC≡CR (28, R = Me; 28’, R = Ph).Treatment of various complexes 29 with n-Bu4NOH yields corresponding ruthenium furyl complexes 31a (R = Me, R’= Et) and 31b (R = Me, R’= CH2CF3).Contents Ibstract III要 VIumbering and Structure of Compounds VIIIraphical Abstract XIIIhapter 1 Introduction 1 1.1. The C2 and C3 Chemistry: Metal Vinylidenes and Allenylidenes 1 1.1-1. Transition-Metal Vinylidene Complexes 1 1.1-2. Metal Vinylidenes in Catalysis 5 1.2. Heterocycles 6 1.2-1. Transition-Metal-Catalyzed Reactions in Heterocyclic Synthesis7 1.3. Motivation of This Thesis 10hapter 2 Catalytic Synthesis of Indoles from Enynes by Ruthenium Complexes 11 2.1. Synthesis of N-Containing 1,7-Enynes 11 2.2. Catalytic Reactions of Enyne N1 12 2.3. Cyclization and [3,3]-Sigmatropic Rearrangement of N2 17 2.4. Steric Effect of Vinylidene Complexes in N3 System 29 2.5. Electronic Effect of N4 System 36hapter 3 Chemistry of Ruthenium Complexes with Propargylic Pyridine 45 3.1. Reactions of Cp(PPh3)2RuCl with Propargylic Pyridine 45 3.2. PPh3 Migration to Form Alkenyl-Phosphonium Complexes 53 3.3. Oxidation of Propargylic Alcohol and the Solvent Effect 61 3.4. Reactions of Cp(PPh3)2RuCl with Protected Propargylic Pyridine 67hapter 4 Chemistry of Ruthenium Complexes with O-Containing 1,7-Enynes 70 4.1. Preparation of Ruthenium Vinylidene and Acetylide Complexes 70 4.2. Formation of Cyclic Oxycarbene Complex 72 4.3. Alkylation Reactions of Ruthenium Acetylide Complexes 81 4.4. Deprotonation of Vinylidenes to Form Ruthenium Furan Complexes 85hapter 5 Summary and Concluding Remarks 87xperimental Section 89eferences 131ppendix A X-ray Crystallographic Data 137 A1. ORTEP Drawing and Crystal Data of Complex 7b’ 137 A2. ORTEP Drawing and Crystal Data of Complex 13 143 A3. ORTEP Drawing and Crystal Data of Complex 14 151 A4. ORTEP Drawing and Crystal Data of Complex 25 16