Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)-Toxicodenane A.

We present the first enantioselective total synthesis and absolute configuration assignment of (+)-toxicodenane A via a nine-step sequence from the readily available material. The synthesis features a desymmetric enantioselective reduction of 2,2-disubstituted 1,3-cyclohexanedione for the synthesis of a chiral 2,2-disubstituted 3-hydroxy cyclohexanone building block, a highly diastereoselective Grignard reaction for the incorporation of an allyl group, and a Lewis acid-mediated intramolecular transacetalation and Prins cascade reaction for the construction of oxa-bridged bicyclic rings.