Atropisomerism and the synthesis of lignans

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Yau, Chi
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A new synthetic methodology was developed to synthesize two chosen lignans, galbulin and cagayanin, with the intent of applying this synthetic scheme for the synthesis of structurally similar lignans. The Stobbe condensation was ideally suited for generating the starting materials for constructing the aryltetralin skeleton. Two successive Stobbe condensations were executed to generate the starting dibenzylidenesuccinates. It was discovered that triflic acid-catalyzed cyclization of these ibenzylidenesuccinates produced the desired aryltetralin lignan structures in good yields. From these aryltetralin skeletons, functional interconversions were performed ultimately to generate the two target natural lignans, galbulin and cagayanin. The dibenzylidenesuccinates, upon treatment with acid, demonstrated some intriguing chemistry. In an attempt to further understand this cyclization step, several other dibenzylidenesuccinates with different substituent patterns were synthesized. These reactions were studied in detail to investigate the effect of the substituent patterns on the outcome of the reaction. Two plausible explanations and detailed mechanisms were postulated to account for the formation of the aryltetralins with literature evidence to support these theories. Methods for coercing the dibenzylidenesuccinate to adopt one atropisomer over the other were studied and the preliminary results are presented. (Abstract shortened by UMI.)