Studies On Some New Organic Synthetic Reactions And Methods Involving Imines

Development of new reactions and new methodologies is one of the most attractive areas in organic chemistry. In this thesis, we have studied a series of new types of imine involved cascade reactions and liquid phase syntheses. The details are summarized below:1. We have developed a three component cascade reaction of aromatic aldehydes, anilines and benzenediazonium-2-carboxylate. The reaction furnishes a rapid and direct construction of substituted phenanthridine rings from readily available starting materials via a one-pot cascade process, provided a 30-member library of 6-aryl-phenanthridines with yields 31～95%. Three component cascade synthesis of 6-aryl-phenanthridines on poly(ethylene glycol) support was also studied. Cleavage from the soluble support under mild conditions afforded a 6-member library of 6-aryl-phenanthridines in high yields (70-90%) with purity (75-96%).2. When we used the aliphatic aldehydes to replace the aromatic aldehydes in the cascade reaction above, surprisingly, 3,4-disubstituded quinolines were obtained, rather than substituted phenanthridines. During further researches, we developed a new approach to 2,3-disubstituded quinolines. The one-pot reaction of aliphatic aldehydes with the electron-rich anilines using 2,2,2-trichloroacetic acid as the catalyst furnishes a rapid and direct construction of substituted quinoline rings, provided a 21-member library of substituted quinolines with yields 64～92%. A plausible process of this reaction is as following: Aldehyde was in equilibrium with the enol form, aldehyde reacted with aniline catalyzed by 2,2,2-trichloroacetic acid to afford imine, the generated imine immediately reacted with enol to form intermediate via intramolecular cyclization. Oxygen in the air apparently acted as an effective oxidant for aromatization of intermediate to afford quinoline. 3. We have developed a new cascade reaction including ketenimine and ketene or aryl azide which provides a new approach to the selective syntheses of (Z)-4-(phenoxymethylene)-azetidin-2-ones and acetimidamides. A plausible mechanism for the cascade process was proposed. Aryl azide reacted with triphenylphosphine and ketenes generated in situ from acid chlorides to afford aza-allene. Its reaction with ketenes generated in situ from acid chlorides afforded (Z)-4-(phenoxymethylene)-azetidin-2-one, thus provided a 14-member library of (Z)-4-(phenoxymethylene)-azetidin-2-one with yields 76～91% and an excellent stereoselectivity. Its reaction with azidobenzene afforded acetimidamide, provided a 14-member library of acetimidamide with yields 70～87%.4. We have developed an efficient liquid-phase synthesis of strongly fluorescent tetraaryl-4,5-dihydro-1,2,4-triazoles via 1,3-dipolar cycloaddition of imines and nitrile imines generated in situ on soluble polymer support. The 1,3-dipolar cycloaddition between soluble polymer-supported nitrilimines generated in situ and imines in parallel one-pot fashion gave the corresponding PEG-supported regioisomeric strongly fluorescent tetraaryl-4,5-dihydro-1,2,4-triazoles as indicated by NMR. Cleavage from the support under mild conditions afforded a 25-member library of strongly fluorescent triazoles with yields 75～95% and purity 77～98%. It was interesting to screen the tetraaryl-4,5-dihydro-1,2,4-triazoles for their optical properties. The correlation between optical properties (especially emission wavelengths and the fluorescence quantum yields) and the molecular structures can currently be described only empirically.5. We have developed the general and efficient methods for the construction of 2,3-dihydro-4-pyridones andβ-lactams on soluble polymer support. The aza-Diels-Alder reaction of Danishefsky's diene with poly(ethylene glycol) (PEG)-bound imines derived from PEG-bound aldehydes, followed by cleavage from the support, afforded a 12-member library of 2,3-dihydro-4-pyridones with yields 75～99% and purity 83～99%, On the other hand, Staudinger reaction of PEG-bound imines with ketenes generated in situ from acid chlorides, followed by cleavage from the PEG, gave a 12-member library of cis-β-lactams with yields 65～99% and purity 63～98%.