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Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
Published on: July 30, 2017
Palladium-Catalyzed C-H Arylation and Azetidination of Pentacyclic Triterpenoids
Vladislavs Kroškins1, Jevgeṇija Lugiṇina1, Rihards La̅cis1
1Institute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, P. Valdena Str. 3, LV-1048 Riga, Latvia.
Abstract:
Synthetic protocols for site-selective palladium-catalyzed C-H arylation and azetidination of pentacyclic triterpenoids have been developed. Betulin, oleanolic, and ursolic acids were converted into primary amines C(28)-NH2 that were further transformed into the corresponding picolinamides. The latter was found to be a suitable directing group for triterpenoid C-(sp 3)-H (het)-arylation with iodo-(het)-arenes in the presence of Pd-(OAc)2/CuBr2/CsOAc system. C-(sp 3)-H (het)-arylation provided yields from 29 to 83%, and the C(22)/C(16) selectivity from 9:1 in the lupane (betulin) series to 19:1 in the oleane and ursane series. The highest isolated yields of C-(sp 3)-H arylated products were achieved with iodoarenes bearing electron-donating groups, but the use of electron-deficient iodoarenes gave a significant proportion of N-picolinoyl azetidine side product. The latter were obtained with good selectivity as major products when 1-iodo-4-nitrobenzene was used as an additive. C-(sp 3)-H arylation revealed C(22)-selectivity in all tested triterpenoid series; however, the azetidination occurred at C(22) in lupane (betulin) series and at C(16) in oleane series. C-(sp 3)-H (het)-arylation and azetidination is a new entry in the derivatization of natural triterpenoids and can be regarded as a useful tool for further exploration in terms of medicinal chemistry.
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