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Abstract
The oxidative dearomatization of aromatic systems can be utilized to rapidly access various cyclohexane containing natural products that possess tertiary alcohols, amines, or quaternary centers within the cyclohexane ring. By beginning with aromatic starting materials, a latent cyclohexane ring is already present in the starting material, reducing synthetic efforts and subsequent manipulation of oxidation states, which can result in more efficient syntheses.
In particular, the dearomatization of resorcinol derivatives should provide useful intermediates because the two olefins in the resultant cyclohexadienone are electronically differentiated. One olefin is part of an enone functionality, while the other is part of a vinylogous ester system. In order to achieve a general and efficient synthesis of such intermediates, the alkylation of resorcinol was examined.
A novel procedure, involving the in situ generation of reactive o-quinone methide intermediates and their subsequent consumption via a 1,4-conjugate addition reaction, was developed. Unlike previous methods for the generation of o-quinone methides, this one is readily controllable, requiring basic conditions at low temperatures, and thereby allowing for the use of varied nucleophiles in the subsequent 1,4-addition to the o-quinone methide. A large variety of alkylated resorcinol derivatives were produced in good yields.
The dearomatization of resorcinol derivatives was investigated in order to achieve the synthesis of scyphostatin. Various resorcinol derivatives were examined and one promising intermediate was advanced towards the scyphostatin core. The synthesis of an intermediate containing the tertiary alcohol and amine stereocenters has been achieved.
