Construction of All‐Carbon Quaternary Stereocenters via Asymmetric Cyclopropanations: Synthesis of Chiral Carbocyclic Pyrimidine Nucleosides

Abstract

An efficient route to synthesize chiral carbocyclic pyrimidine nucleoside analogues containing all-carbon quaternary stereocenters has been established via the asymmetric intermolecular cyclopropanation of N1-vinylpyrimidines and aaryl diazoesters. With 2 mol% of chiral dirhodium (II) carboxylate complex as the catalyst, a variety of chiral carbocyclic cytosine or uracil nucleoside analogues were obtained in good yields (up to 96% yield), high diastereoselectivities (> 20:1 dr), and excellent enantioselectivities (up to 99% ee).

Catalytic Asymmetric Intermolecular Cyclopropanation of a Ketone Carbene Precursor by a Ruthenium(II)‐Pheox Complex

“…Optically active cyclopropane derivatives have received considerable attention in the fields of organic and pharmaceutical chemistry owing to the biological activities of cyclopropanes . The transition metal‐catalyzed asymmetric cyclopropanations of diazoacetates with olefins using chiral Cu,– Rh,– Ru,– Co,– and Ir [m] catalysts have been reported with excellent stereoselectivities. In most cases, steric hindrance plays an important role in obtaining high stereoselectivities (Scheme , reaction 1).…”

Enantioselective Synthesis of α-Aryl-β-Aminocyclopropane Carboxylic Acid Derivatives via Rh(II)-Catalyzed Cyclopropanation of Vinylsulfonamides with α-Aryldiazoesters

“…In addition, gram-scale synthesis was conducted under standard reaction conditions and gave product 3aa in 89% yield with no decreased stereocontrol (Scheme a). Although several methods including our strategy for the synthesis of α-aryl-β-ACCs have been developed, ,− there are rare reports for their application in peptide synthesis. This prompted us to further explore the incorporation of 3aa into peptides.…”

“…Compared with the traditional multistep methods involving a key Curtius rearrangement for the synthesis of β-ACCs, the transition-metal-catalyzed asymmetric [2 + 1]-cyclopropanation of enamines with α-diazoesters has proven to be one of the more powerful strategies in terms of high stereocontrol and step economy. − In general, most of these cyclopropanation approaches are limited to H-acceptor type of α-diazoesters, whereas the reactions with donor–acceptor α-aryldiazoester counterparts, which would result in conformationally more constrained α-aryl-β-aminocyclopropane carboxylic acid derivatives (α-aryl-β-ACCs) bearing one quaternary carbon stereogenic center vicinal to the amino-substituted carbon with potentially new or improved properties, have not yet been fully investigated. ,− …”

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

“…To address this issue, several ingenious asymmetric catalytic methods have been developed to selectively access this structural motif. However, these examples are limited to three- and five-membered carbocyclic nucleoside analogues . To date, highly enantioselective construction of chiral six-membered carbocyclic nucleosides in a straightforward approach is rare.…”