10.1021/jo981075c
The research focuses on the synthesis of enantiopure highly substituted trans-8a-hydroxydecahydroisoquinolines, which are significant components of over 500 alkaloids and hold synthetic interest due to their potential biological activity. The study employs a diastereoselective approach involving a sequential intramolecular Diels-Alder (IMDA) reaction and oxanorbornene nucleophilic ring opening, utilizing chiral perhydrobenzoxazines derived from (-)-8-aminomenthol as a chirality inductor. Key chemicals in the process include 2-furaldehyde, (-)-8-((3′-butenyl)amino)menthol, aluminum hydride, pyridinium chlorochromate (PCC), potassium hydroxide, and triethylaluminum, among others. The method allows for the introduction of different substituents at C-1 and C-8 in the final isoquinolines regio- and stereoselectively, leading to the synthesis of a variety of enantiopure isoquinoline derivatives with four stereocenters, three of which are contiguous, and with known absolute configuration. The conclusions of the research highlight the efficiency of this concise and stereocontrolled synthetic method for potentially important biologically active molecules, demonstrating a five-step synthesis from the easily accessible (-)-8-aminomenthol.