| Summary: | <p>A method to enable the synthesis of conduramines and their <em>N</em>-substituted derivatives (enantiopure or racemic form) in six steps (five steps for <em>N</em>-substituted derivatives) from cyclohexa-1,4-diene is reported. Key features of this reaction sequence include a preparation of benzene oxide that is amenable to multigram scale, and its efficient ring-opening upon treatment with a primary amine. Epoxidation of the resultant amino alcohols (40% aq HBF<sub>4</sub> then <em>m</em>-CPBA) is accompanied by hydrolytic ring-opening in situ to give the corresponding <em>N</em>-substituted conduramine derivatives directly. These may undergo subsequent <em>N</em>-deprotection to give the parent conduramines, as demonstrated by the preparation of enantiopure (−)-conduramine A1, (−)-conduramine A2, and (−)-conduramine E2 (the latter two for the first time). The selectivity of the epoxidation reaction is proposed to be the result of competitive ammonium-directed and hydroxyl-directed epoxidation processes, followed by either direct (S<sub>N</sub>2-type) or conjugate (S<sub>N</sub>2′-type) ring-openings of the intermediate epoxides.</p>
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