Efficient syntheses of new heteroarotinoids through functional pyridylzinc reagents 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 heteroarylzinc reagent, readily accessible from 2,6-dibromopyridine, may undergo a selective palladium-catalyzed carbon-carbon bond-forming reaction to yield the corresponding 6-substituted-2-bromopyridines 13. Further manipulation of the remaining bromine atom in 13 to give the zinc derivative 14, and subsequent coupling with ethyl 4-iodobenzoate under palladium catalysis conditions afforded 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.