Iodine(III)-Mediated Enantioselective Oxidative Contraction of Dihydropyranones.

The γ-butyrolactone motif is promising in pharmaceuticals and natural products with various biological activities. The oxidative contraction of dihydropyranones mediated by hypervalent iodine (HVI) reagents is an efficient approach of preparing this motif. We show that, using readily available chiral HVI reagents, numerous enantioenriched γ-butyrolactones are accessible.

Diastereoselective Synthesis of Arabino- and Ribo-like Nucleoside Analogues Bearing a Stereogenic C3' All-Carbon Quaternary Center.

The synthesis of novel nucleoside analogues bearing a C3' all-carbon quaternary center and a C2'-hydroxy substituent is described. The all-carbon stereogenic center was generated through an intramolecular 7- attack of a silyl-tethered allyl moiety on a tertiary radical using photoredox catalysis. Subsequent allylic oxidation and diastereoselective hydride reductions provided the hydroxy substituent at C2', which then controls the stereoselective introduction of pyrimidine nucleobases on the corresponding furanose scaffold.

Photoredox-Catalyzed Stereoselective Radical Reactions to Synthesize Nucleoside Analogues with a C2'-Stereogenic All-Carbon Quaternary Center.

The design of novel nucleoside analogues bearing a C2' all-carbon quaternary center is described. The construction of this all-carbon stereogenic center involves the use of photoredox catalysis to initiate an intramolecular attack of a silyl-tethered vinyl functionality on a tertiary radical. Density functional theory calculations were performed to explore the origin of the high diastereoselectivity obtained through the preferred 5-exo-trig cyclization mode.

Iodine(III)-Mediated Contraction of 3,4-Dihydropyranones: Access to Polysubstituted γ-Butyrolactones.

Functionalized γ-butyrolactones are privileged structures in the field of medicinal chemistry; they are found in numerous natural products and synthetic compounds with diverse biological activities. The oxidative ring contraction of 3,4-dihydropyran-2-one derivatives represents a promising yet underappreciated strategy to access these compounds. To the best of our knowledge, very few examples of this strategy have been reported, with limited investigation of the influence of stereogenic centers on the starting dihydropyranones.