Carbolithiation of <i>o</i>-Amino-(<i>E</i>)-Stilbenes: Diastereoselective Electrophile Substitution with Applications to Quinoline Synthesis

A regioselective carbolithiation of o-amino-(E)-stilbenes has been achieved with a series of alkyllithiums when THF is employed as the reaction solvent. The use of other solvents, such as diethyl ether or hydrocarbons, leads to a pronounced loss in regioselectivity. Moreover, high levels of diastereoselectivity have been obtained following reaction of the lithiated intermediate in THF with different electrophiles such as MeOD, CO2, and Bu3SnCl. It was shown that diastereoselectivity was influenced by the ortho-amino substituent and the alkyllithium utilized for carbolithiation with N-Boc substituent and t-BuLi proving optimal. In the case of carbolithiated intermediate 3a, obtained from the reaction of N-Boc substituted stilbene with t-BuLi, 1H and 13C NMR analysis revealed predominantly one diastereoisomer which was stable at room temperature. Application of the carbolithiation/electrophile reaction methodology to the synthesis of six-membered quinoline ring systems is demonstrated with substituted 3,4-dihydroquinolin-2-ones, 1,2,3,4-tetrahydroquinolines, 1,4-dihydroquinolines, and quinolines all prepared by a common cascade route.