Concise Total Synthesis and Stereochemical Analysis of Tetraponerines T3 and T4

摘要

An efficient stereocontrolled preparation ofntetraponerines T3 and T4 is detailed. The sequence takesnadvantage of two consecutive stereoselective aminoallylationsnof appropriate aldehydes with chiral tert-butanesulfinamide andnin situ generated allyl indium species. The absolutenconfiguration of the carbon stereogenic center at the aminalnmoiety is thermodynamically controlled. This was ascertainednon the basis of an exhaustive DFT configurational study ofntetraponerines, which fulfils the lack of detailed structuralninformation for these systems. It was found that the transtransoid-nconfiguration of the AB rings is the most stable geometry for T3 and T4. However, the C ring prefers a cis-configurationnin T3 (ttc-T3) and a trans-fusion in T4 (ttt-T4). Regarding their dynamic behavior, low activation barriers were found by DFTncalculations for the inversion of the nitrogen at the indolizidine framework, allowing rapid equilibration between the majornconfigurations (ttc and ttt) in T3 and T4.