Alkaloids of the Flora of Siberia and Altai: XX. Synthesis of 5-Aryl(hetaryl)-Substituted Anthranilic Acid Esters

摘要

Cross-coupling of methyl 2-acetylamino-5-bromobenzoate and 5'-bromolappaconitine with aryl-, furyl-, pyridyl-, and 5-acetylthiophen-2-ylboronic acids or l-(2-fluoroquinolin-3-yl)-4,4,5,5-tetrarnethyl-1,3,2-dioxaborolane gave the corresponding 5-aryl(hetaryl)-substituted anthranilic acid derivatives. The use of the two-phase toluene-water system as reaction medium and addition of tetrabutylammonium bromide allows the cross-coupling to be accomplished under mild conditions. The catalytic system Pd(dba)2-AsPh3 was found to be efficient in the cross-coupling of methyl 2-acetylamino-5-bromobenzoate with furyl- and pyridylboronic acids, whereas the system Pd(OAc)2-(o-Tol)3P ensured good results in the reactions of 5'-bromolappaconitine with hetarylboronic acids. Facile esterification at the C~8-OH and C~9-OH groups of the aconitane skeleton was observed in the reactions of 5'-bromolappaconitine and 5'-phenyllappaconitine with phenylboronic acid. 5'-Bromo-8,9-O-(phenylboranediyl)lappaconitine under the Suzuki reaction conditions underwent hydrolysis of the boronic ester moiety with formation of the cross-coupling product of 5'-bromolappaconitine with phenylboronic acid.