Microwave-Assisted Pd/Cu-Catalyzed C-8 Direct Alkenylation of Purines and Related Azoles: An Alternative Access to 6,8,9-Trisubstituted Purines

Abstract

An efficient microwave-assisted palladium/copper comediated C-8 direct alkenylation of purines with styryl bromides has been developed. The method is regioselective, functional group tolerant, rapid, and compatible with other related azoles. Combined with subsequent nucleophilic substitution, it provides an easy access to new 6,8,9-trisubstituted purines.

Palladium‐Catalyzed Amidation and Amination of 8‐Iodopurine

“…[22,23] In general, the sulfanyl group can serve as a leaving group after oxidation to the corresponding sulfone for subsequent substitution with suitable nucleophiles. [24][25][26][27][28][29][30][31] The key step was the regioselective lithiation/iodination of the 8-position of 6-phenylsulfanyl derivative 2 by LDA at -78°C (Scheme 1) by using conditions previously described for the lithiation/iodination of 1. [32,33] Initially, the coupling of 6-chloro-8-iodopurine (4) with benzamide as a representative amide was investigated on the basis of our previously reported conditions [Pd 2 (dba) 3 / Xantphos, Cs 2 CO 3 in dioxane at 100°C].…”

Oxazole

“…A C2-alkenylation of purines and heteroarenes including oxazole utilizing styryl bromide was reported. 55 Palladium acetate and CuI function as co-catalysts; however, it is crucial to premix CuI with phenanthroline for 30 min prior to addition of the other reagents. Reaction times could be shortened from 16 h to 30 min and premixing of CuI with phenanthroline was no longer required using microwave irradiation.…”

Regioselective CH Imidation of Five‐Membered Heterocyclic Compounds through a Metal Catalytic or Organocatalytic Approach

“…Regioselectivity was achieved through a metal catalytic or organocatalytic approach. [6] Over the past decades, a variety of elegant methods have been developed for the intermolecular C À H arylation, [7] alkylation, [8] olefination [9] and alkynylation [10] of azoles. [4] The five-membered heterocycles pyrrole, furan, and thiophene with amine substituents are important synthetic intermediates and employed widely in medicinal chemistry.…”

“…[4] The five-membered heterocycles pyrrole, furan, and thiophene with amine substituents are important synthetic intermediates and employed widely in medicinal chemistry. [6] Over the past decades, a variety of elegant methods have been developed for the intermolecular C À H arylation, [7] alkylation, [8] olefination [9] and alkynylation [10] of azoles. Therefore, direct functionalization of these compounds is economically attractive and of important synthetic usage.…”

“…[5] These skeletons have classically been prepared by cyclocondensation reactions, forming the heterocyclic ring in the key step from two functionalized precursors. [6] Over the past decades, a variety of elegant methods have been developed for the intermolecular C À H arylation, [7] alkylation, [8] olefination [9] and alkynylation [10] of azoles. Transition-metal-catalyzed synthetic transformations have been considered as one of the most reliable and powerful tools for connection of such chemical bonds, giving complex molecular structures in an efficient and economical manner.…”