METALATION AND METAL-ASSISTED BOND FORMATION IN PI-ELECTRON DEFICIENT HETEROCYCLES

Work is reviewed on the regio- and chemo-selective introduction of carbon substituents into pi-electron deficient heterocycles. Halogeno and trifluoromethanesulfonyl derivatives have been coupled with organostannanes and organozinc reagents in Pd-mediated reactions. Acyl, aryl or heteroaryl, and unsaturated or saturated alkyl derivatives are formed. Organomanganese reagents are used in ketone syntheses. Methods for preparing metallopyrimidines, especially stannopyrimidines, are described. Palladized pyrimidines have been isolated. Stannopyrimidines are used in Pd-catalyzed coupling reactions. Pyrimidinylcerium derivatives are superior to lithio analogs in most reactions. Organometallics (Li, Mg, Cu) form C-C bonds by 1:1-adduct formation in an activated, vacant electrophilic position, and the products are aromatized by oxidation. Organotitanium reagents show high regioselectivity. Tetraisopropoxy-zirconium is used for regioselective dihydro formation. N-C bonds are formed by Pd(0)-catalyzed allylation reactions. Stereo- and regio-specific syntheses of carbonucleosides from pyrimidines and purines are described. The regiochemistry in Pd(0, II)-catalyzed allylic rearrangements from O to N in 2-pyrimidinones depends on the oxidation state of the palladium and on the nature of substituents. Pyrimidinyl allylic carbonates rearrange with loss of CO2. The regiochemistry in the N-allyl substituent may change because the allylation is reversible. Allylic rearrangement has been used in the preparation of a carbocyclic uridine analog.