Efficient syntheses of new heteroarotinoids through functional pyridylzincreagents and palladium-catalyzed cross-coupling reactions

A convergent synthesis of heteroarotinoids 4, 5a, and 5b, bearing chromene rings in association with pyridyl or ethynylpyridyl moieties, from 6-bromo- 2-pyridylzinc chloride (11) is described, This now functional heteroarylzin c reagent, readily accessible from 2,6-dibromopyridine, may undergo a selec tive palladium-catalyzed carbon-carbon bond-forming reaction to yield the c orresponding 6-substituted-2-bromopyridines 13. Further manipulation of the remaining bromine atom in 13 to give the zinc derivative 14, and subsequen t coupling with ethyl 4-iodobenzoate under palladium catalysis conditions a fforded heteroarotinoid 4. Coupling of the substituted bromopyridines 13 or the triflate 22 with appropriate alkynes under Sonogashira conditions give the corresponding heteroarotinoids 5a, 5b, and 6.