Two one-pot oxidative cyclization strategies to spiroacetals are described herein. The first approach utilizes a Lewis acid-mediated Ferrier reaction for the initial fragment coupling followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-initiated oxidative carbon–hydrogen bond cleavage and cyclization. The second approach relies on a Heck cross coupling for fragment assembly followed by a DDQ-mediated dehydrogenation of enol ethers into enones and subsequent acid-induced cyclization. These methods provide mild convergent protocols to spiroketal subunits, which are ubiquitous in natural products, medicinal drugs, and chemical libraries.
Cyclopropane-substituted allylic ethers undergo carbon–hydrogen bond cleavage to form stable oxocarbenium ions upon reaction with DDQ. Significantly, in the presence of an appending nucleophile, facile ring closure occurs to yield highly functionalized tetrahydropyrans with no accompanied cyclopropane scission. This methodology was showcased during the total synthesis of the sponge-derived macrodiolide clavosolide A
