Synthesis of Spirocyclic C‐Arylglycosides and ‐Ribosides by Ruthenium‐Catalyzed Cycloaddition

Abstract

Spirocyclic C-arylglycosides were synthesized from the appropriately protected delta-gluconolactones. Addition of lithium acetylide followed by glycosylation with 3-(trimethylsilyl)propargyl alcohol converted the delta-gluconolactones into silylated diynes. After desilylation, subsequent ruthenium-catalyzed cycloaddition of the resultant diynes with alkynes or chloroacetonitrile gave spirocyclic C-arylglycosides in good yields and selectivity. This strategy was also extended to the synthesis of spirocyclic C-arylribosides from the known gamma-ribonolactone derivative. Moreover, silver-catalyzed iodination of the sugar diynes followed by ruthenium-catalyzed cycloaddition with acetylene delivered spirocyclic C-iodophenylglycosides and -ribosides, which were subjected to palladium-catalyzed C-C bond-forming reactions and copper-catalyzed coupling with nitrogen heterocycles to lead to various derivatives.

Ruthenium-Catalyzed Cycloadditions to Form Five-, Six-, and Seven-Membered Rings

“…Later, Yamamoto reported the synthesis of spirocyclic C -ribosides (Scheme ) and C -arylglycosides (Scheme ). , Use of monoiodo-terminated 1,6-diynes delivered C -( ortho -iodoaryl)­ribosides and C -( ortho -iodoaryl)­glycosides, which were derivatized via palladium- or copper-catalyzed C–C or C–N couplings, respectively (not shown).…”

Anomeric Spiro-Annulated Glycopyranosides: An Overview of Synthetic Methodologies and Biological Applications

“…The reaction proceeded through a one-pot sequential process with carbodiimides adding to the carboxylic acid and then boron trifluoride etherate induced intramolecular N-sialylation with high α-selectivity. The [2 + 2 + 2] cycloaddition strategy of alkynes could be readily applied for the synthesis of spiro-annulated glucosides under either rhodium [42] or ruthenium catalysis [43]. The cycloaddition of the propargyl ketoside with a 1,2-triple bond 55 with acetylene afforded the desired benzo-fused spiro-glucoside 56 in high yields (Scheme 18).…”

Syntheses of Heterocycles via Alkyne Cycloadditions Catalyzed by Cyclopentadienylruthenium-Type Complexes

“…61 The synthesis of the heterocyclic analogs of this fascinating molecular target was attempted by the cycloaddition of glucose-derived unsymmetrical 1,6-diyne 132 with chloroacetonitrile 18 in the presence of 5 mol% 1 at room temperature to afford spirocyclic C-pyridylglycoside 133 in 83% yield as a single isomer (Scheme 32a). 61 The synthesis of the heterocyclic analogs of this fascinating molecular target was attempted by the cycloaddition of glucose-derived unsymmetrical 1,6-diyne 132 with chloroacetonitrile 18 in the presence of 5 mol% 1 at room temperature to afford spirocyclic C-pyridylglycoside 133 in 83% yield as a single isomer (Scheme 32a).…”