Furo pyridine, lithiation

Lithiation of compounds 8.110 generally takes place at the 2-position [as, e.g., in thieno[3,2-b]pyridine (84JHC785), furo[3,2-c]pyridine (83T1777), and thieno[2,3-b]pyridine (74JHC355)]. However, in thie-no[2,3-6]pyrazine lithiation occurs at the 5- and 6-positions in a 17 83 ratio (80JHC1019). Compounds of type 8.111 undergo lithiation as follows imidazo[l,2-[Pg.236]

Cyclization of iodopyiidinyl aUyl ethers derived fom dihalopyridines and sodium aUyUc oxides leads to formation of furo[2,3-fc]pyridines 292, furo[3,2-c]pyiidines 293, and furo[2,3-c]pyridines 294 by a Heck mode of reaction (Scheme 101). In the reaction sequences, the initial step in the preparation of iodopyridine aUyl ethers involves regioselective lithiation of 3-fluoro, 2-fluoro-, and 4-chloropyridines with LDA. Subsequently, the lithiated species are treated with iodine as electrophile. A variety of iodopyiidinyl ethers have been prepared from dihalopyridines and sodium aUyhc oxides and subjected to the Pd-catalyzed cyclization reactions with formation of the furoannulated pyridine products. When the allyl groups carry a 2-substituent as in stracture 295, hydridopaUadium elimination is prevented. Instead, sodium formate reductive elimination of the palladium substituent gives the product 296. The isomeric structures 297 and 298 are available similarly. ... 

While the metalation of pyridines is well understood, the regioselective lithiation of furopyridines was studied to map the best way to prepare functionalized derivatives of furo[3,2-fc]pyridines (13JOC5618). A number of aryl bromides, including bromopyridines were studied to determine the optimal amount of f-butyllithium to use in the preparation of aryl sulfonamides via metal-halogen exchange (130L2954). 

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