Copper mediated stereoselective synthesis of C-glycosides from unactivated alkynes

Abstract

A highly stereoselective rapid C-glycosylation reaction has been developed between glycal and unactivated alkynes in the presence of coppertriflate and ascorbic acid at low catalyst loading and at room temperature. A wide variety of glycals and aryl acetylenes participate in the reaction smoothly. TfOH generated during the reduction of Cu(OTf)2 by ascorbic acid may be the active catalyst for the glycosylation.

Methods for 2-Deoxyglycoside Synthesis

“…C -Glycosyl alkynes are attractive carbohydrate synthetic tools that can undergo further transformations to achieve more complex carbohydrate analogues. To that respect, Mukherjee and co-workers 366 have recently developed a new methodology to access C -alkynyl sugars by copper-mediated glycosylation of glycals with unactivated alkynes using copper triflate (10 mol %) and ascorbic acid at room temperature. The reaction was shown to work with a range of glycals (e.g., glucal, galactal, and rhamnal) such as 352 , providing the corresponding C -glycosyl compounds 353 with high α-selectivity ( Scheme 96 ).…”

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

“…To our delight TLC showed full consumption of the starting materials in 2 min and yielded the desired product 3a in 80% yield ( Table 1 , entry 1). The structure and stereochemistry were elucidated by a comparison of the chemical shifts to that of reported values [ 35 ]. Also, the stereochemistry of the resulting product 3a was unambiguously established as α by NOESY spectra, indicating cross peaks between H-1, H-6 and H-4.…”

“…It was established that the system was tolerant to a wide variety of electron-donating as well as electron-withdrawing terminal alkynes to give the corresponding products 3a–e in excellent yields and selectivity. It is noteworthy that the earlier reported [ 35 ] single-step strategy failed to yield a product with aliphatic alkynes, so that we applied the method to aliphatic alkynes. The reaction with cyclopropylacetylene, hept-1-yne and oct-1-yne maintained a high selectivity and gave the corresponding products 3f–h in 54, 42 and 39% yield, respectively.…”

“…Thus, the triflic acid generated in situ consequent to the formation of trimethylsilylacetylene activates the tri- O -acetyl - D - glucal forming an oxonium ion intermediate, which is attacked by trimethylsilylacetylene to give the corresponding product ( Scheme 3 , reaction 2). The stereochemistry of the reaction products is possibly determined by the coordination between two π-electron orbitals of the oxocarbonium ion and the acetylene groups, while the stereoelectronic control allows the α-pseudo-axial orbital to form the bond [ 35 ].…”

“…A consequence of the prior activation of alkynes is the involvement of multiple steps and thus loss of yields. Recently, Mukherjee and co-workers [ 35 ] have reported a one-step C -alkynylation of glycals by using metal in combination with a co-oxidant, i.e., Cu(OTf) 2 with ascorbic acid. However, a drawback of the method is its limited applicability to arylacetylenes only and its restricted selectivity to reactions performed in the solvent acetonitrile ( Scheme 1 ).…”