Work

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

Year: 2025

Type: article

Abstract: ( 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 C 8a 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 C 8 -substituted derivative 13 depending on the reaction temperature. An expeditious synthesis of the Myrioneuron -type alkaloid (−)-myrioxazine A from 13 is reported.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.5c00321