Diastereo- and Enantioselective Synthesis of Bisbenzannulated Spiroketals and Spiroaminals by Ir/Ag/Acid Ternary Catalysis.

We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]-spiroketals in high efficiency with generally high diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). In this procedure, readily available o-alkynylacetophenones undergo cycloisomerization to generate isochromenes in situ that participate in stereoselective allylation/spiroketalization sequence with 2-(1-hydroxyallyl)phenols. Meanwhile, 2-(1-hydroxyallyl)anilines were also compatible in this cascade reaction, furnishing structurally novel bisbenzannulated [6,6]-spiroaminals with good diastereoselectivities (8 : 1-12 : 1 dr) and excellent enantioselectivities (98 %->99 % ee). Moreover, experimental studies and theoretical calculations were performed to illustrate the reaction mechanism and stereochemistry.

Enantioselective Synthesis of Spiroketals and Spiroaminals via Gold and Iridium Sequential Catalysis.

The enantioselective cascade reaction between racemic 2-(1-hydroxyallyl)phenols and alkynols/alkynamides was realized by using a gold and iridium sequential catalytic system. In this procedure, the in situ generated exocyclic vinyl ethers or enamides undergo the asymmetric allylation/spiroketalization with π-ally-Ir amphiphilic species, which provides an efficient and straightforward access to spiroketals and spiroaminals with excellent enantioselectivities. Moreover, racemic 2-(1-hydroxyallyl)anilines were also suitable in this reaction along with a kinetic resolution process, affording enantioenriched spiroaminals and 2-(1-hydroxyallyl)anilines in good yields. The synthetic utility of this method has been demonstrated by efficient enantioselective synthesis of the analogue of Paecilospirone.