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UBC Theses and Dissertations

Construction of functionalized nitrogen heterocycles using 2-(diphenylphosphoryl)oxygen-1,3-butadienes in multicomponent [4+2] cycloaddition reactions He, Qiuyu


This dissertation presents research work on hetero-Diels-Alder reactions using 2-diphenylphosphoryloxy-1,3-butadienes and imines for the construction of six-membered nitrogen heterocycles. Chapter 1 provides an overview of hetero-Diels-Alder reactions that primarily focuses on imines and enol-based dienes. Chapter 2 describes hetero-Diels-Alder reactions between 2-diphenylphosphoryloxy-1,3-butadienes and imines under the promotion of iron(III) chloride. Twelve examples of 2-diphenylphosphoryloxy-1,3-butadienes were synthesized, and eighteen cycloaddition products were constructed in 30–91% isolated yields. Relative configurations of products formed in diastereomeric mixtures were analyzed by 2-dimensional NMR spectroscopy, and the diastereomeric ratios ranged from 2:1 to >20:1. The utility of the enol phosphate functionality was demonstrated in manipulations of the cycloaddition products in transition metal catalyzed cross-coupling reactions. Chapter 3 describes the multicomponent hetero-Diels-Alder reactions using dienes from Chapter 2, amines, and aldehydes through in situ generation of iminium species under the promotion of boron trifluoride diethyl etherate. The reactions were carried in non-distilled dichloromethane without the use of inert atmosphere. Thirty-one examples of cycloaddition products were presented with a diverse scope of aromatic aldehydes, aliphatic aldehydes, N-sulfonyl amines, and N-carbamoyl amines. Chapter 4 describes a sequence of cycloaddition–cross-coupling–oxidation reactions to construct functionalized pyridines. The N-Fmoc substituted cycloaddition products were subjected to Pd(0)-catalyzed Kumada coupling reactions with varied Grignard coupling partners. The Fmoc protecting group in the cross-coupling products was deprotected using piperidine. A subsequent addition of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidized the heterocyclic ring to an aromatic pyridine structure. Twenty examples of disubstituted pyridines and one example of trisubstituted pyridine were constructed in 17–88% yields over two synthetic steps. Twelve examples of fluorescent 4-biphenylpyridines were constructed and could potentially be applied in light-luminating materials. Their wavelengths of maximum emission lied in the range of 349–389 nm.

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