Total Synthesis of Stemoamide, 9a-epi-Stemoamide, and 9a,10-epi-Stemoamide: Divergent Stereochemistry of the Final Methylation Steps
Total syntheses of stemoamide, 9a-epi-stemoamide, and 9a,10-epi-stemoamide by a convergent A + B ring-forming strategy is reported. The synthesis required a diastereoselective late-stage methylation of the ABC stemoamide core that successfully enabled access to three of the four possible diastereomeric structures. For the natural stemoamide series, the diastereoselectivity can be rationalized both by kinetic and thermodynamic arguments, whereas for the natural 9a-epi-stemoamide series, the kinetic selectivity is explained by the prepyramidalization of the relevant enolate.
Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones
A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions. peerReviewed
CCDC 1973338: Experimental Crystal Structure Determination
Related Article: Imre Pápai, Petri M. Pihko, Juha H. Siitonen, Dániel Csókás|2020|Synlett|31|1581|doi:10.1055/s-0040-1707201
CCDC 1973339: Experimental Crystal Structure Determination
Related Article: Imre Pápai, Petri M. Pihko, Juha H. Siitonen, Dániel Csókás|2020|Synlett|31|1581|doi:10.1055/s-0040-1707201