Ni-Catalyzed Cross-Coupling of 2-Iodoglycals and 2-Iodoribals with Grignard Reagents: A Route to 2-C-Glycosides and 2'-C-Nucleosides

The synthesis of 2-C-glycals and 2-C-ribals was achieved in good yields using a nickel-catalyzed cross-coupling between 2-iodoglycals and 2-iodoribal respectively and Grignard reagents. The prepared 2-C-glycals and ribals were then transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides and 2'-C-2'-deoxynucleosides. The developed method was applied to the synthesis of a 2-chloroadenine 2'-deoxyribonucleoside - a structural analogue of cladribine (Mavenclad (R), Leustatin (R)) and clofarabine (Clolar (R), Evoltra (R)), two compounds used in the treatment of relapsing-remitting multiple sclerosis and hairy cell leukemia.

Automated summary

Good yields of 2-C-glycals and 2-C-ribals were achieved through a nickel-catalyzed cross-coupling reaction between 2-iodoglycals and 2-iodoribals using Grignard reagents. The synthesized compounds were further transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides, and 2'-C-2'-deoxynucleosides. This method was successfully applied to the synthesis of a 2-chloroadenine 2'-deoxyribonucleoside, an important analogue of cladribine and clofarabine used in the treatment of multiple sclerosis and hairy cell leukemia.