Ligand-Governed Regio- and Enantioselective [2 + 2 + 2] Cycloaddition of 1,7-Enynes: Assembly of the Benzo[<i>c</i>]chromen-1-ol Backbone and Access to Enantioenriched Cannabinol Bioisostere

We herein report a regioselective synthesis of the benzo[<i>c</i>]chromenol core via cationic rhodium-catalyzed [2 + 2 + 2] cycloaddition of 1,7-enynes with tetrolic acid derivatives. With the selection of an appropriate ligand, both regioisomers could be obtained in excellent regiomeric ratio and enantiomeric excess. The regioselectivity was governed by different factors, which was suggested by computational studies. Furthermore, the asymmetric synthesis of an axially chiral cannabinol bioisostere candidate was achieved by the transformation from central chirality to axial chirality. Demonstration of the synthesis of a natural compound was also depicted.