Studies On The Transition Metal-Catalyzed Intramolecular Hydroarylation Reactions Of Allenes Or Alkynes

Heterocyclic compounds have been widely applied in medicine, pesticides, dyes, and polymers, thus, the corresponding synthetic methods have been a hot topic in organic synthesis. Based on previous efforts in our group, the main theme of my dissertation has been focused on gold and platinum-catalyzed intramolecular hydroarylation of allenes or alkynes to construct differently substituted carbazoles, benzo[b]thiophenes, benzo[b]furans, dibenzofurans and optically active 1,4-dihydroarenes. This dissertation includes six chapters:1. Based on the PtCl2-catalyzed cycloisomerization of 1-(indol-2-yl)-2,3-allenols, we have reported a new AuCl-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols, providing an efficient route to differently substituted carbazoles, which proceeds by a selective 1,2-alkyl or aryl shift via a gold-carbene intermediate. The migratory aptitude of 1,2-alkyl or aryl migration has been established. DFT calculations support the originally hypothesized 1,2-migration on the metal-carbene intermediate. In order to show the synthetic potential of our method, we have realized the highly efficient synthesis of isomukonidine, clausine L, mukonidine, glycosinine, mukonal, and clausine V.2. We further reasoned that benzo[b]thiophenes, benzo[b]furans, and dibenzofurans could be afforded by using thiophenes, furans, and benzo[b]furans instead of the indole unit in the starting allenol derivatives. Thus, we have developed a general Au-catalyzed reaction of 1-heteroarylalka-2,3-dienyl acetates, providing a series of benzo[b]thiophenes, benzo[b]furans, and dibenzofurans. Two possible pathways are involved in this reaction as supported by the mechanistic studies.3. A simple and efficient method for the synthesis of 1,4-dihydroarenes by gold-catalyzed 6-endo hydroarylation reaction of benzylic allenes has been developed. Furthermore, asymmetrical intramolecular cyclization of enantioenriched allenes has been realized to offer a practical and convergent route to aromatic ring-fused six-membered cyclic compounds containing a chiral stereocenter, i. e., 1,4-dihydronaphthalenes, 1,4-dihydrodibenzo[b]thiophenes, and 4,7-dihydrobenzo[b]- thiophenes by applying dinuclear (dppm)Au2Cl2/AgOTf to ensure the high efficiency of chirality transfer. With the help of Dr. Haoyang Wang of Shanghai Institute of Organic Chemistry, ESI-MS experiments have been applied to detect the reactive dinuclear intermediates successfully, which unveiled the mechanism.4. Based on AuCl3-catalyzed reaction of 1-(indol-2-yl)-3-alkyn-1-ols to provide differently substituted carbazoles, we have develoed an efficient AuCl(PPh3)/AgBF4-or PtCl4-catalyzed reaction of 1-(indol-2-yl)-2,2-dialkyl-substituted-3-alkyne-l-ols. Different 1,2-alkyl migration of different pathways have been established:1,2-alkyl migrated carbazoles could be obtained exclusively in the presence of AuCl(PPh3)/AgBF4 via a Wagner-Meerwein type 1,2-alkyl shift, whereas in some cases the use of PtCl4 afforded inverted regioselectivity forming 1,2-methyl migrated carbazoles involving a platinum-carbene intermediate.5. We also expanded the reaction scope of PtCl4-catalyzed reaction of 2-(indol-2-yl)-3,3-dialkyll-substituted-4-alkyn-2-ols to provide tetrasubstituted carbazoles. A novel PtCl4-catalyzed rearrangement reaction to differently tetrasubstituted carbazoles has been found, and a rationale has been proposed for this transformation.6. A simple and efficient [IPrAuCl]/AgSbF6-catalyzed cyclization reaction to a series of differently poly-substituted 2-oxygenated carbazole derivatives has been developed. Based on careful mechanistic study, a possible mechanism involving 1,3-migration of benzoate group forming allene, Au+-mediated cyclization-elimination forming gold-carbene intermediate and subsequent highly selective 1,2-migration has been proposed for the formation of carbazoles. Finally, the first total synthesis of recently isolated naturally occurring carbazole alkaloid karapinchamine A in 5.2 gram has been realized in 6 steps from commercially available chemicals without applying any protection-deprotection.