We have developed an efficient route for the synthesis of the perhydroquinoline core of aspidophytine (1), the right-hand domain of the heterodimeric indole alkaloid haplophytine (2). This densely functionalized perhydroquinoline core (3) displays four contiguous stereocenters including an all-carbon quaternary center. The synthetic sequence features a highly effective Diels-Alder reaction between a carbamate-substituted siloxy diene and 2-bromoacrolein, which can also be rendered enantioselective through the use of a chiral Co(III)-salen catalyst. The electron-rich aniline moiety was installed on the perhydroquinoline core via a TBSOTf-mediated intramolecular aza-Michael reaction, and the relative stereochemistry of the aza-Michael product was confirmed by X-ray crystallographic analysis.

Studies directed toward the synthesis of aspidophytine

253rd National Meeting (2017)

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