Cascade approaches to decahydroquinoline ring systems

The aims of this project were to develop a cascade approach towards decahydroquinoline frameworks (Scheme I) and apply this to the synthesis of decahydroquinoline-containing natural products such as lycopodine, cermizine B and lepadin D (Scheme I).Scheme I.Several linear precursors were synthesized via a modular strategy. For example, lycopodine linear precursor i was synthesized in a total of 12 steps (Scheme II).Scheme II.Conditions for cyclization and hydrogenation were tested, with the diastereoselectivity examined in each system. For example, the lepadin linear precursor ii produced two decahydroquinolines iii and iv upon cyclization (Scheme III).Scheme III.It was found that the diastereoselectivity was dependent on the ring substituents and variation of the hydrogenation conditions could change the facial selectivity of enamine reduction.