[4+3]CYCLOADDITION REACTIONS OF CYCLIC OXYALLYLS IN NATURAL PRODUCT SYNTHESIS

The [4 + 3] cycloadditions of oxyallyls and related allyl cations to 1 ,3-dienes have been widely utilized for the stereocontrolled construct ion of seven-membered carbocycles. By virtue of the spectator skeleton , the key variant of utilizing cyclic oxyallyls, i.e., by embedding an oxyallyl function in cyclic compounds, provides a conceptually attrac tive and operationally efficient route to other medium-sized carbocycl es and heterocycles in addition to seven-membered rings. The resulting architecturally complex, polycyclic cycloadducts contain not only suf ficient functionality, but also well-defined facial differentiation us eful for subsequent elaboration. [GRAPHICS] Studies comparing the know n [4 + 3] cycloaddition protocols employing a six-membered cyclic oxya llyl or aminoallyl and a cyclic 1,3-diene are described. The scope and limitations of the [4 + 3] cycloadditions under the Fohlisch and Schm id conditions, two methods of choice, are delineated. Of particular no te is use of decalone-derived oxyallyls which affords the highly order ed tetracyclic bridged cycloadducts containing considerable structural and topographical complexity. Discussion will follow on oxidative cle avage of the ketone bridge present in the cycloadducts by the method o f Suarez to generate the medium-sized ring system. Also included is th e further oxidation of the resulting alkyl iodides which permits a fac ile preparation of bridgehead olefins. Finally, preliminary implementa tions of the oxyallyl cycloaddition and Suarez cleavage for the synthe sis of eight-membered cyclic ethers and taxane diterpenes are presente d. [GRAPHICS] We believe the initial phase of research described herei n serves as a testimonial for considerable versatility and utility off ered by this new synthetic methodology utilizing cyclic oxyallyls in t he [4 + 3] cycloaddition reactions.