Palladium-Catalyzed C–S Bond Formation as a Tool for Latent–Active Glycosylation

Abstract

A high-yielding palladium-catalyzed C–S cross-coupling is presented for utilization in carbohydrate chemistry as a key transformation for attachment of a second chelating sulfur atom that allows the exploitation of a latent–active glycosylation strategy with Cu­(OTf)2 as the promoter. The novel approach employs o-Br-benzyl thioglycosides as latent glycosyl donors and o-SMe-benzyl thioglycosides as the active counterparts.

Transition‐Metal‐Mediated Glycosylation with Thioglycosides

“…Jensen and co‐workers recently reported the novel ortho ‐(methylthio)benzyl thioglycosides as effective donors capable of the Cu(OTf) 2 mediated remote activation pathway [106] . It has been proposed that having two sulfur atoms, the anomeric one and o ‐SMe‐functionalized benzyl, the activation would occur through a metal chelating effect.…”

“…Jensen and co-workers recently reported the novel ortho-(methylthio)benzyl thioglycosides as effective donors capable of the Cu(OTf) 2 mediated remote activation pathway. [106] It has been proposed that having two sulfur atoms, the anomeric one and o-SMe-functionalized benzyl, the activation would occur through a metal chelating effect. After investigating various metal triflates, only Cu(II) and Fe(III) salts were found to be effective, at which point the authors decided to procced with less hygroscopic Cu(OTf) 2 .…”

Nickel(II)‐Mediated C−S Cross‐Coupling Between Thiols and ortho‐Substituted Arylboronic Acid

“…[10][11][12] Since Migita and co-workers reported palladium-catalyzed cross-coupling reactions between aryl halides and thiols, [13,14] transition-metal-catalyzed crosscoupling reactions between thiols and aryl halides or their equivalents have attracted significant attention as one of the most powerful and straightforward methods of forming CÀ S bonds (Scheme 1a). [15][16][17][18][19] Many metal salts, containing Pd, [15,[19][20][21][22][23][24][25][26] Cu, [18,[27][28][29][30][31][32][33] Ni, [8,[34][35][36][37][38][39] Co, [40] Zn, [41] Au, [42,43] Ag, [44] and Rh, [45] have been used to effectively catalyze CÀ S cross-coupling reactions. Remarkable progress has been made in the field of transitionmetal-catalyzed cross-coupling reactions allowing us to access structurally diverse and polyfunctionalized sulfides.…”

Thiocarbonyl as a Switchable Relay-Auxiliary Group in Carbohydrate Synthesis

“…A latent−active strategy and latent glycosylation were recently developed to link several building blocks together to streamline oligosaccharide synthesis. 11,12 The formation of a glycosidic linkage generates a new stereogenic center at the anomeric carbon (C1); therefore, the control of stereoselective glycosylation is one of the most challenging tasks and has long been a major bottleneck for carbohydrate chemistry. The stereoselectivity outcome has been found to be elusive with different functionalities/ reactivities of donors.…”

“…On consideration of the glycosylation reaction, a glycosyl donor bearing a leaving group on the anomeric center is activated by the promoter to generate an oxocarbenium ion that is further intercepted by the hydroxyl group of the adjacent acceptor. A latent–active strategy and latent glycosylation were recently developed to link several building blocks together to streamline oligosaccharide synthesis. , The formation of a glycosidic linkage generates a new stereogenic center at the anomeric carbon ( C 1); therefore, the control of stereoselective glycosylation is one of the most challenging tasks and has long been a major bottleneck for carbohydrate chemistry. The stereoselectivity outcome has been found to be elusive with different functionalities/reactivities of donors.…”