Synthesis of Chiral Six-Membered Carbocyclic Purine Nucleosides via Organocatalytic Enantioselective [3 + 3] Annulation

Abstract

A direct route to chiral six-membered carbocyclic purine nucleoside analogues with three chiral stereocenters, including a chiral tetrasubstituted carbon center, via a highly enantioselective [3 + 3] annulation has been established. With the application of Takemoto's catalyst, various chiral six-membered carbocyclic purine nucleoside analogues were obtained in high yields (up to 89%) with moderate to good diastereoselectivities (up to 90:10 dr) and excellent enantioselectivities (92-98% ee). Furthermore, diverse chiral six-membered carbocyclic purine nucleoside analogues were generated by simple transformations.

Electrochemical enantioselective dihydroxylation reaction of N-alkenyl nucleobases for the construction of chiral acyclic nucleosides

“…11 To address these issues, it is critical to employ a carbon felt anode with a large specific surface area and KI as a non-metal reaction mediator in order to shorten the reaction time and diminish cathodic metal reduction. In line with our continued interest in nucleosides, 12 we herein report the study of the electrochemically driven asymmetric dihydroxylation reaction for the synthesis of various chiral acyclic nucleosides (Scheme 1). Our results show that the reaction features (a) a high TON (up to 950), (b) exogenous-oxidant-free conditions, (c) an operationally convenient undivided cell setup, (d) scalability through electro-oxidation, and (e) a structurally diverse substrate scope.…”

Current Strategies on the Enantioselective Synthesis of Modified Nucleosides

“…(Scheme 1b). 30 Further, chiral cyclopentene nucleoside analogues 18 containing a quaternary stereocenter were established via a highly enantioselective [3+2] annulation of Morita-Baylis-Hillman (MBH) carbonates 17 with -purine-substituted acrylates 16. After screening various catalysts, (S)-SITCP catalyst 19 was found to give the best yield and excellent enantioselectivity.…”

Further developments of β,γ-unsaturated α-ketoesters as versatile synthons in asymmetric catalysis

“…Moreover, in consideration of the facile deprotonation at both α -positions, aliphatic ketones could be employed as alternative dinucleophiles for C3 synthons for [3 + 3] annulation reactions. In this context, a catalytic asymmetric Michael addition-proton transfer-aldol reaction cascade reaction of α -purine-substituted acetones 96 with β,γ -unsaturated α -ketoesters was accomplished by Niu and Guo et al., in 2018 ( scheme 13 D) ( Huang et al., 2018 ). By using bifunctional thiourea catalysis, chiral six-membered carbocyclic purine nucleoside analogues 97 bearing three chiral stereocenters including a chiral tetrasubstituted carbon center were readily created in high yields (65–89%) with excellent diastereo- and enantioselectivities (92–98% ee, 80:20 to 90:10 dr).…”