Tandem Vinylogous Mannich and Hetero Diels-Alder Reactions: Concise Total Synthesis of (±)-Alstoscholarisine E

ABSTRACT The shortest synthesis to date of (±)-alstoscholarisine E was accomplished in 15.2% overall yield requiring only seven linear steps from commercially available reagents. The approach features a tandem vinylogous Mannich reaction and an intramolecular hetero Diels-Alder reaction to access the cis-oxahydroisoquinolone core. Following the coupling of this cis-oxahydroisoquinolone subunit with a 3-methylindole derivative via a Suzuki reaction, a novel tactic to induce the challenging diastereoselective reduction of the cyclic vinyl ether moiety was discovered. Completion of the synthesis was achieved using a new procedure we developed for iridium-catalyzed, reductive formation of aminals from tertiary lactams, thereby expanding the utility of tertiary amides and lactams as surrogates for iminium ions.