Enantioselective Access to Decahydroquinolines Bearing a C4a or C8a Quaternary Stereocenter from a Common Intermediate Total Synthesis of (-)-Myrioxazine A.

(R)-Phenylglycinol-derived perhydrooxazoloquinoline 2 provides stereoselective access to angularly substituted enantiopure decahydroquinolines (DHQs). Reaction of 2 with appropriate Grignard reagents leads to cis-DHQs bearing a C8a aza-quaternary stereocenter, whereas reaction of 2 with Michael acceptors followed by reductive removal of the 2-phenylethanol of the chiral inductor gives rise to cis- or trans-DHQs bearing a C4a all-carbon quaternary stereocenter depending on the hydride used for the cleavage of the oxazolidine C-O bond. Theoretical studies have clarified the mechanistic intricacies of the reaction of 2 with Michael acceptors, providing arguments for a proper understanding of the observed stereoselectivity. Finally, the reaction of 2 with formaldehyde is reversible, allowing the regioselective formation of either the angularly substituted hydroxymethyl derivative 12 or the C8-substituted derivative 13 depending on the reaction temperature. An expeditious synthesis of the Myrioneuron-type alkaloid (-)-myrioxazine A from 13 is reported.