Enantioselective Access to Decahydroquinolines Bearing a C_4a or C_8a Quaternary Stereocenter from a Common Intermediate Total Synthesis of (−)-Myrioxazine A

(<i>R</i>)-Phenylglycinol-derived perhydrooxazoloquinoline <b>2</b> provides stereoselective access to angularly substituted enantiopure decahydroquinolines (DHQs). Reaction of <b>2</b> with appropriate Grignard reagents leads to <i>cis</i>-DHQs bearing a C_8a aza-quaternary stereocenter, whereas reaction of <b>2</b> with Michael acceptors followed by reductive removal of the 2-phenylethanol of the chiral inductor gives rise to <i>cis</i>- or <i>trans</i>-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 <b>2</b> with Michael acceptors, providing arguments for a proper understanding of the observed stereoselectivity. Finally, the reaction of <b>2</b> with formaldehyde is reversible, allowing the regioselective formation of either the angularly substituted hydroxymethyl derivative <b>12</b> or the C₈-substituted derivative <b>13</b> depending on the reaction temperature. An expeditious synthesis of the <i>Myrioneuron</i>-type alkaloid (-)-myrioxazine A from <b>13</b> is reported.