Enantioselective 1,3-Dipolar [6+4] Cycloaddition of Pyrylium Ions and Fulvenes towards Cyclooctanoids

Organocatalytic enantioselective 1,3-dipolar [6+4] cycloadditions of pyrylium ion intermediates with fulvenes promoted by a chiral primary amine catalyst have been developed to proceed in moderate to good yields and high enantioselectivities. The resultant chiral bicyclo[6.3.0]undecane scaffold containing a transannular bridging ether is densely functionalised providing a rigid scaffold for further manipulations. Computational studies give important insights into the role of the primary amine catalyst. Analysis of the reaction shows that the catalytic reaction proceeds in a step-wise manner and rationalises the stereochemical outcome of the reaction. Several stereoselective complexity-generating transformations, facilitated by the diverse functional groups and transannular bridge, are presented, highlighting the versatility of the core towards a number of the cyclooctanoid natural products.