| Following the development of a method for the generation of o-QMs from o-BOC salicylaldehydes and alcohols with organometallic reagents, our group revealed o-QMs generated in this manner undergo inverse demand [4+2] cycloadditions to form diastereoselective chroman backbones. This process was envisioned for the construction of chiral benzylic junctions, where the preferred methods have been catalytic asymmetric hydrogenation and asymmetric conjugate addition. As the prior processes often require lengthy reaction times and are often substrate dependent, an additional asymmetric method would likely prove to be complementary. The first reported examples of enantioselective [4+2] cycloadditions of o-QMs with a chiral enol ether were utilized in the first total synthesis of (+)-mimosifoliol and the formal synthesis of (+)-tolterodine.;Our interest in the rapid assembly of structurally complex chromans prompted us to also pursue the syntheses of type-A PAs, diinsinin and diinsininol. In 1996, these compounds were isolated from the rhizome of Sarcophyte piriei and were previously used in folk medicine for their analgesic and anti-inflammatory properties. To the best of our knowledge, there are no previous synthetic endeavors addressing these targets or similar type-A PA compounds in the literature. The first synthesis of (+/-)-diinsininone, the aglycone of diinsinin, will be presented utilizing a Path A biosynthetic route, the condensation of a flavanone and a benzopyrilium salt. |
