Regioselective ortho-Lithiation of Halopyridines. Syntheses of ortho-Disubstituted Pyridines and a Convenient Generations of 3,4-Pyridyne

me regioselective onho-lithiation of 3-chlm (4), 3-fluoro-(7).3 -h m o -(lo), 2chloro (22).and 4-chlmpyridine (25) with lithium diisopropylamide affords, after quenching with various electrophiles, the corresponding onho-disubstih~ted pyridines in yields from 16-9696.Halogen-metal exchange between 4-i&3-chlmpyridine (6a) and ten-butyllithium or n-butyllithium provides a wnvenient generation of 3.4-pyridyne (1).which is trapped in a Diels-Alder reaction with furan and 2.5-dimethylfuran to give 31 and 32 (2438%).Heteroatom-facilitated metalation reactions have had a major impact on the design and execution of organic synthesis over the past decade, particularly those reactions involving aromatic and heternaromatic subsh'ates.'.'In co~ection with a synthetic approach to the ellipticine (6H-pyrido[4,3-b]carbmle) family of antitumor alkaloids, we desired to generate and uap 3,4-pyridyne (1) in a Diels-Alder reaction.3At that time, the only two techniques for generating and efficiently trapping 1 with dienes (e.g., fwan) involved tedious, multi-step syntheses of 33pyridyne precursorsf 5 Following the completion of the present research, there have appeared in the literature several other good methods for the generation of 3,dpyridyne (1)6 t~his papx is dedicated lo Professor Ted Taylor in celebration of his 70th birthday, with affection and admimion from a fellow Vermonter.