Copper mediated A3-coupling reaction for the preparation of enantioselective deoxy sugar based chiral propargylamines using bifunctional ligand l-proline.

An efficient three component coupling of aromatic aldehyde, deoxy sugar based alkyne (α-2-deoxy propargyl glycoside) and heterocyclic amine have been refluxed to synthesize stereoselective chiral propargylamines with good to excellent yield using only CuI catalyst along with bifunctional ligand l-proline. This method has proved to be applicable in wide range of substrates and found highly enantioselective with respect to earlier reported methods. In addition, l-proline was found as a chiral source which demonstrated that it could be developed as a highly enantioselective method for the construction of deoxy sugar based chiral propargylamines. The ligand l-proline was used for the first time in enantioselective A3-coupling reaction of α-2-deoxy propargyl glycosides involving substituted aromatic aldehyde and heterocyclic amines. Herein, we have synthesized 15 novel compounds based on A3-coupling reaction and structures of all the enantioselective compounds were characterised by TLC and NMR spectroscopy.

Synthesis of glycoconjugate mimics by 'click chemistry'.

Stereo-defined 2-deoxy propargyl glycosides can be used for the synthesis of corresponding 1,4-disubstituted sugar derived triazoles by using only CuI and stereo-defined sugar azide derivatives. The click chemistry which involves copper (I) catalysed alkyne-azide 1,3-dipolar cycloaddition, was used to prepare a library of glycoconjugates mimics. Different sugar propargyl-2-deoxy-O-α-d-glycopyranoside derivatives and ß-glycopyranosyl azide derivatives were coupled using catalyst CuI to yield triazole glycoconjugates. The catalyst CuI (2.5 eq.) in CH3CN was found to be most efficient for the synthesis of 1,4-disubstituted triazole scaffolds affording up to 94% of optimized yield and with retention of the anomeric configuration of the starting glycosides. The key feature of this methodology is the absence of sodium l-ascorbate/ascorbic acid which is most active substrate of current research with strong potential for click reactions. In this article, the library of novel stereoselective deoxy sugar derived triazole glycoconjugates have been synthesized and structures were determined by the 1H, 13C & 2D NMR spectroscopy.

L-Proline/CeCl3·7H2O-NaI mediated stereoselective synthesis of α-2-deoxy glycosides from glucal.

Glucal with different alcohols can be converted into the corresponding 2-deoxy glycosides without Ferrier rearrangement in high yield by treatment with eco friendly transition metal based catalysts [CuCl3·2H2O-NaI (A) or CeCl3·7H2O-NaI (B)] and chiral amine ligand L-proline at various reaction conditions which were optimized for stereoselectivity. The catalyst CeCl3·7H2O-NaI (B) and ligand L-proline in toluene, was found to be much more efficient and high atom economic for the stereoselective glycosidation of propargyl alcohol with glucal, afforded exclusively α-2-deoxy propargyl glycoside in 98% optimized yield. The ligand L-proline was used for the first time in stereoselective glycosidation of α-2-deoxy glycosides involving glucal and alcohols.