Pd-catalyzed allylic substitution of purin-8-yl(allyl) acetate: Route to (E)-alkenylpurines

Abstract

Dedicated to Professor Pavel Kočovský on the occasion of his 60th birthday.C 8 -Alkenylpurines were synthesized starting from purin-8-yl(allyl) acetates using Pdcatalyzed allylic substitution. The described protocol allows, by reaction of purin-8-yl(allyl) acetates with stabilized nucleophiles, an access to novel (E)-8-alkenylpurine derivatives under Pd 2 dba 3 ·CHCl 3 catalysis in dry THF in yields ranging from 31 to 76%. A wide range of nucleophiles showed exclusive E-alkene formation, however, ethyl nitroacetate gave mixture of E/Z-alkenes. On contrary, purin-2-yl(allyl) acetates reacted smoothly only with dimethyl malonate.

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

“…18,19 A Pd-catalyzed allylic substitution for the preparation of various C-8-alkenylated purines has also been reported. 20 In addition, transition-metalcatalyzed C−H bond functionalization of purines has gained significant attention in recent years. In particular, the direct arylation 21−26 and to a lesser extent direct alkenylation 27 and benzylation 28 have been developed.…”

“…As a consequence, a plethora of methodologies for the construction and functionalization of purines has been intensively explored. − In the context of a medicinal chemistry program, we were interested in generating a variety of C-8 vinyl-substituted purines based on the direct alkenylation of a suitably substituted purine, which could subsequently be used for further functionalization on the other positions. Increasing interest in C-8 substituted purines has driven the development of more or less efficient methods for their elaboration, including the heterocyclization of aminopyrimidine derivatives with aldehydes, carboxylic acids , or amides, metal-catalyzed cross-coupling reactions of appropriate C-8-halogenated purines, − and direct metalation. , A Pd-catalyzed allylic substitution for the preparation of various C-8-alkenylated purines has also been reported . In addition, transition-metal-catalyzed C–H bond functionalization of purines has gained significant attention in recent years.…”