A Modular Approach to Aryl-C-ribonucleosides via the Allylic Substitution and Ring-Closing Metathesis Sequence. A Stereocontrolled Synthesis of All Four α-/β- and d-/l-C-Nucleoside Stereoisomers

Abstract

Iridium(I)-catalyzed allylation of the enantiopure monoprotected copper(I) alkoxide, generated from (S)-5a, with the enantiopure allylic carbonates (R)-9a,b has been developed as the key step in a new approach to C-nucleoside analogues. The anomeric center was thus constructed via a stereocontrolled formation of the C-O rather than C-C bond with retention of configuration. The resulting bisallyl ethers 15a,b (≥90% de and >99% ee) were converted into C-ribosides 29a,b via the Ru-catalyzed ring-closing metathesis, followed by a diastereoselective dihydroxylation catalyzed by OsO(4) or RuO(4) and deprotection. Variation of the absolute configuration of the starting segments 5a and 9a,b allowed a stereocontrolled synthesis of all four α/β-D/L-combinations.

Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

“…The method by Hartwig et al was also applied in the synthesis of aryl- C -ribonucleosides by Kočovský and co-workers . Nevertheless, a detailed screening of reaction parameters was necessary due to the steric bulk of the nucleophile, and two approaches were used.…”

“…The method by Hartwig et al was also applied in the synthesis of aryl-C-ribonucleosides by Kocǒvskýand coworkers. 347 Nevertheless, a detailed screening of reaction parameters was necessary due to the steric bulk of the nucleophile, and two approaches were used. In the first approach, linear allylic carbonates were reacted with an enantiomerically pure copper alkoxide, 497d, using Hartwig's conditions.…”

Rhodium Porphyrin Catalyzed Regioselective Hydrogenolysis of 1,2-Diarylcyclopropanes with Water as the Hydrogen Source

“…With 1,2-Bis(4-fluorophenyl)cyclopropane (1f). The reaction with 1f (23.0 mg, 0.1 mmol) was heated in air at 200 °C for 60 h to afford 1,3-bis(4-fluorophenyl)propane 36 (2f; 0.052 mmol) in 52% yield and 1,3-bis(4-fluorophenyl)propene 37 (3f; 0.011 mmol) in 11% yield.…”

A New Insight into the Stereoelectronic Control of the Pd0‐Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran‐2‐ones via an Unusual 1,3‐Transposition

“…The classical Tsuji–Trost Pd 0 ‐catalyzed allylic substitution represents a robust, stereo‐ and regioselective methodology that has been frequently utilized in organic synthesis as an indispensable tool. The reaction is known to proceed via η 3 ‐complexes that are formed from allylic esters, typically with inversion of configuration, where the Pd approaches the allylic moiety from the side opposite to the leaving group ( A in Scheme ) . Retention pathway for the formation of η 3 ‐complexes ( B ) has also been reported, especially in those instances, where the leaving group can coordinate the approaching palladium and thus steer its approach to the C=C bond .…”

“…Retention pathway for the formation of η 3 ‐complexes ( B ) has also been reported, especially in those instances, where the leaving group can coordinate the approaching palladium and thus steer its approach to the C=C bond . In all these reactions, good alignment of the π‐orbitals of the double bond with the σ bond of the leaving group (X) has been regarded as a prerequisite for the reaction to occur . In other words, the allylic leaving group should be positioned perpendicularly to the plane of the C=C bond ( A / B ).…”