Novel Generation Of O-Quinodimethanes From Benzo[C]Oxepines And Their Application For The Construction Of Diversity Framework

The formation of carbon-carbon bond is a basic research topic in organic synthesis which do not only play an important role in theoretical research, but also provide means for logic design of novel reactions. The construction of carbon ring skeleton has important meanings for the synthesis of complexity functional structures. The metastable or transient intermediates, due to their high reactivity, are extensively been used as synthesis synthons for the development of effective strategies in the constructing of target compounds in cascade reaction. The elusive intermediate o-quinodimethane (o-QDM) has attracted much attention from both theoretical and synthetic chemists. During the past decades, an explosive amount of enthusiasm in the research area of the o-quinodimethane chemistry has been developed in a variety of fields including the syntheses of steroids and other natural products, their application in the emerging fullerene chemistry, their employment as the first nitric oxide cheletropic trap, their utility as building blocks in the syntheses of polymeric materials or in materials science, and their implications in different electrochemical and physical studies. In this thesis, we originally developed a novel and efficient generation protocol of o-quinodimethane and provided evidences for their existence via the observation of their decay modes and trapping reaction. This novel generation of o-QDM approach were further applied in the synthesis of carbon ring skeletons with diversity such as naphthalene, benzocyclobutene, dibenzocyclooctadiene, tetrahydronaphthol derivatives. In the mechanism exploretion part, we also studied the ring opening reaction of benzo[c]oxepine. The main contents are as follows:In chapter 1, we introducted the structure and properties of o-quinodimethanes and reviewed the generation of this intermediate and described the related precursors, followed by their application in organic synthesis. Based on the previous studies, we proposed our research strategy for this thesis.In chapter 2, naphthalene skeleton is one of the most fundamental structures of polyaromatic structures, which were basic building blocks in pharmaceuticals, polycyclic aromatic electronic materials and organic synthesis catalyst. An unexpected rearrangement aromatization of benzo[c]oxepine has been observed to synthesize substituted naphthalenes. This observation was further exploited to develop an efficient approach for the construction of naphthalenes from simple and commercially available 1,3-dicarbonyl compounds and 1,2-bis(halomethyl)benzene compounds via a new domino reaction sequence.In chapter 3, the formation of naphthalene from benzo[c]oxepine in the above chapter need further inverstigation and the assumptive transient intermediate o-QDM also need to be further verified. In this part, a series of benzo[c]oxepines were synthesized and indanone containing benzo[c]oxepines demonstrated great variety reactivity attributed to the extension of the delocalized π-system by the indanone substituent, which thermodynamically stabilized and increased the lifetime of the o-quinodimethane structure. We were fortunately obtained the decay products of o-QDM including naphthalene, benzocyclobutene, dibenzocyclooctadiene and o-methylstyrene derivatives, which provided convincing evidences for the existence of this elusive intermediate. According to the literature survey, this work provided the most comprehensive and systematic study of the deay modes for ο-QDM intermediates.In chapter 4, as cis-dienes, o-QDMs have a remarkable Diels-Alder reactivity and are often used as building blocks in the synthesis of cyclic organic compounds by intermolecular [4+2] trapping. In this part, the trapping reactions of o-QDM intermediates were achieved with dienophiles for the synthesis of polysubstituted tetrahydronaphthols in high regioselectivity. The synthesis of the related products do not only provided further evidences for the existence of this elusive intermediate but also developed an efficient approach for the construction of tetrahydronaphthols in high regioselectivity.In chapter 5, on the basis of the above research, the applications of this novel generation of o-QDM were exploited for the synthesis of (3-substituted naphthalenes. An efficient and practical method for the synthesis of cyano, sulfonyl and phosphoryl substituted naphthalene derivatives via the rearrangement aromatization of benzo[c]oxepine has been developed. The formation of naphthalene compounds first experienced the C-alkylation and O-alkylation to give benzo[c]oxepines, then electrocyclic of o-QDM gennerated in-situ and followed by aromatization. The system holds the advantages of metal catalysts free, and mild reaction conditions.In chapter 6, the above research of chapter 2 to 5 provided a novel generation of o-QDM and their reativity, while the process of the generation of o-QDM from benzo[c]oxepines need further investigation. In this part, exploratory research was experimented for the ring-opening reaction of benzo[c]oxepines. The addtion of nucleophilic reagents caused ring-opening reaction of benzo[c]oxepines and gave benzyl alcohols compounds.In chapter 7, In addition to the project of "Novel Generation of o-Quinodimethanes from Benzo[c]oxepirtes and Their Application for the Construction of Diversity Framework",I also carried on the study of non-covalent interaction synthesis that design and construction of higher order assembly structures using supramolecular synthons-during the period for doctoral degree. In this charpter, we investigated the H-bond inducted assembly of glycoluril based clips. A series of three glycoluril derivatives were examined through crystallographic characterization to reveal a highly conserved amide···amide homosynthon, with intermolecular R.22(8) hydrogen bonding interactions. As expected, the intermolecular hydrogen bonding interactions promoted dimerization of building blocks even in the presence of competing pyridine rings and various solvent molecules. These robust dimmer synthons were then connected to one-dimensional chain through C-H···O interactions and further extended to two-dimensional layer by additional C-H···π interactions. This robust hydrogen bond motif was achieved without interference from competing intermolecular interactions and significant changes in the hydrocarbon core and as such, has much potential for application in a supramolecular synthon for solid-state design.In chapter 8, we investigated the π-π interactions inducted assembly of glycoluril based clips. A series of seven glycoluril derivatives were examined through crystallographic characterization to reveal a substituent effects controled self-association of molecular clips in the crystalline state. The research in this part provided a novel dimerazation motif which had never been observed in the previous reports. In the self-assembly of these glycoluril based clips, coplanarly and conjugationly played an important role in their dimerazation.In chapter 9, X-ray crystallography, NMR spectroscopy and molecular modeling were used to study the conformation behavior of glycoluril clip. The results of the computational studies revealed the stability of four conformers remained the order aa>as≈sa>ss in both gas and solvation models, while solvation decreased the relative energies of each conformer dramatically. In solid phase, X-ray crystallographic analysis indicated the studied compound presented conformational polymorphism when it crystallized in various solvents. We fortunately obtained the single crystal of aa and as conformers of the same glycoluril clip. The X-ray crystallographic analysis as conformer in this report first provided crystallographic evidence of the conformers of glycoluril clip. Unlike to solid state, the conformers interconvert rapidly in solution and therefore cannot be detected on NMR timescale.