A STEREOSELECTIVE AND ENANTIOSELECTIVE APPROACH TO CLAVULONES FROM TRICYCLODECADIENONE USING FLASH VACUUM THERMOLYSIS

The stereo- and enantioselective synthesis of clavulones 6 and their analogues 48 is described. gamma-Hydroxycyclopentenones (-)-13 and 44 which are key intermediates in this approach, ape obtained from enantiopure endo-tricyclo[5.2.1.0(2,6)]decadienones (+)-14 and (+)-20 in 6 and 8 steps, respectively, Crucial steps are the reductive epoxy ring opening in compounds (+)-25 and 39 to give dap corresponding diols (+)-27 and 40 and the thermal cycloreversion of tricyclodecenones (+)-27 and 41 using the technique of flash vacuum thermolysis (FVT), The synthesis of enantiopure (-)-13 represents a formal total synthesis of clavulones 6. The synthesis of clavulone analogues (-)-48E and (-)-48Z (X= CH2OH) is completed by condensation of 44 with aldehyde 45 followed by elimination of water and removal of the protective THP-group.