Highly Selective One-Pot Synthesis Of Macrocyclic Oligomers And Research For Its Mechanism

In the past few decades, the access to efficient synthesis of aromatic macrocycles has attracted increasing attentions due to their demonstrated and many other potential applications. One-pot H-bonding-assisted macrocyclization strategy has been recenly elaborated that has become the dominant method for the rapid construction of H-bonded macrocyclic foldamers of various structures. POCl3and BOP have been shown recently to allow the circular methoxybenzene-based pentamers and pyridone-based pentamers to be formed from their building blocks respectively, and do not yield any circular fluoropentamer from its corresponding monomeric fluorobenzene amino acids, thereby limiting the development of their functions. It is therefor of outstanding interest to us to continue searching for suitable one-pot macrocyclization reagents capable of selectively producing fluoropentamer from its corresponding monomeric building block.The main works in the thesis are described below:In order to identify a suitable macrocyclization reagent for one-pot synthesis of fluoropentamer, we designed and synthesized three different types of amine-ester monomer, and screened various metal salts,unexpectedly identifying trimethyl aluminum (AlMe3) as a macrocyclization reagent for highly selective one-pot synthesis of strained macrocyclic aromatic hexamers. Through a series of experiments, we have investigated the effects of temperature, time, solvent, Lewis base, monomer concentration, concentration of AlMe3on the one-pot macrocyclization reaction, and have successfully obtained the optimal conditions involving monomeric methoxybenzene amine ester at100mM and the use of3equivalents AlMe3with reaction temperature set at70℃and a reaction time of12h in tetrahydrofuran (THF) in the absence of Lewis base. According to temperature-dependent distributions of intermediate and circular oligomers from one-pot cyclohexamerization and the previously elucidated bimolecular mechanism for POCl3-mediated one-pot cyclohexamerization, we speculated that the strained haxamer is also generated from bimolecular reactions, rather than by a chain-growth mechanism. That is to say, two acyclic intermediates (for instance, a dimer and a tetramer molecule or two trimer molecules) may react with each other to produce cyclic hexamers. The substrate scope was then examined by applying the optimized macrocyclization coditions to monomeric26b-26d whose exterior alkoxy chains differ by lengths. Except for26b for which no macrocyclization product was observed,27c and27d both were produced satisfactorily from26c and26d.