Origin of the Base‐Dependent Facial Selectivity in Annulation Reactions of Nazarov‐Type Reagents with Unsaturated Indolo[2,3‐a]quinolizidine Lactams

The methyl-substituted Nazarov reagent 4 stereoselectively reacts with Nind-Boc indoloquinolizidine lactams to give the expected H-3/H-15 cis pentacyclic yohimbine-type adducts when using DBU as the base. However, a dramatic change of the facial selectivity was observed when the reaction was performed in the presence of Cs2CO3, leading to the corresponding trans adducts. This annulation is the key step of an stereocontrolled synthesis of the 17a-carba-analog of the heteroyohimbine alkaloid akuammigine. Theoretical calculations were used to rationalize the facial selectivity of these double Michael addition reactions.