TiCl4-Mediated Diastereoselective Tandem Reactions of Functionalized Keto Esters and Dihydrofurans: Synthesis of Substituted Tricyclic Hexahydro-2H-benzocycloheptafurans

We report highly diastereoselective TiCl₄-mediated tandem reactions that provide functionalized tricyclic benzocycloheptafurans in an efficient manner. The reaction of a range of substituted α-keto esters with dihydrofuran or phenyl dihydrofuran in CH₂Cl₂ set up a tandem reaction sequence, providing fused ring heterocycles. The precursor-substituted keto esters were synthesized efficiently by using a two-step sequence. The reaction accessed relatively unexplored hexahydro-2H-benzocycloheptafuran ring systems with three contiguous chiral centers, providing excellent diastereoselectivity and good to excellent yields. A metal triflate catalyzed acyloxy oxocarbenium-mediated ring opening of the tandem reaction products also provided convenient access to substituted benzo[7]annulene cores.