A bridgehead organolithium reagent, the retro-Nazarov reaction, and 4+3 cycloadditions with a nicotinic acid derivative

Substitution reactions of molecules with halogens at the bridgehead position are not widely used in synthetic organic chemistry. This is mainly due to the inaccessibility or difficulty of making molecules containing bridgehead halides. Our approach demonstrates the easy synthesis of such compounds through the 4+3 cycloaddition reaction. Lithium-halogen exchange forms the stable bridgehead organolithium. This organolithium has been quenched by a number of electrophiles, forming a wide array of substitution products at the bridgehead position.; The retro-Nazarov ring-opening reaction was first shown to occur with 2-bromo-4-t-butoxy-cyclopentanones substituted at the 3-position with an aryl or alkenyl group. The minimum structural requirements for this reaction to proceed were studied and in the process the natural product turmerone was synthesized.; The 4+3 cycloaddition reaction of the methyl salt of 5-hydroxynicotinic acid methyl ester and several dienes produced a number of interesting cycloadducts. These cycloadducts were studied with respect to the regioselectivity and stereoselectivity from the cycloaddition.