Combining triflic acid promoted glycosylations of trichloroacetimidates with reductive opening of benzylidene acetals with triflic acid and triethylsilane as one-pot procedures provides easy access to a wide range of di-and branched trisaccharides.Protein-and lipid-bound saccharides are ubiquitous in biological systems involved in many important molecular processes such as fertilization, embryogenesis, neuronal development, hormone activities, and the proliferation of cells and their organization into specific tissues. 1, 2 These interactions are also important in health science and are involved in the invasion and attachment of pathogens, inflammation, metastasis, blood group immunology, and xenotransplantation. [3][4][5] A major obstacle to advances in glycobiology is the lack of pure and structurally well-defined carbohydrates and glycoconjugates. These compounds are often found in low concentrations and in micro-heterogeneous forms, greatly complicating their isolation and characterization. In many cases, well-defined oligosaccharides can only be obtained by organic synthesis. [6][7][8][9] Although the methods for oligosaccharide synthesis have improved considerably during the past decade, the construction of complex carbohydrates remains a significant challenge due to the combined demands of elaborate procedures for glycosyl donor and acceptor preparation and the requirements of regio-and stereoselectivity in glycoside bond formation. To streamline the preparation of complex oligosaccharides, one-pot multi-step approaches for selective monosaccharide protection and oligosaccharide assembly are being pursued, which do not require intermediate work-up and purification step and hence speed-up the process of chemical synthesis considerably.10 ,11 For example, the observation that acetal formation, regioselective reductive opening of arylidene acetals, reductive etherification and acetylation can be catalyzed by triflic acid (TfOH) or trimethylsilyl triflate (TMSOTf) made it possible to program these gjboons@ccrc.uga.edu. Supporting Information Available Experimental procedures and 1 H and 13 C NMR spectra. This information is available free of charge via the Internet at http://pubs.acs.org. To further streamline the process of oligosaccharide assembly, we report here a strategy whereby a regioselective opening of a benzylidene acetal and glycosylations are combined in a one-pot multi-step synthetic procedure. The attraction of the approach is that it makes it possible to assemble branched oligosaccharides by a one-pot procedure; a task that cannot readily be accomplished by chemoselective, orthogonal and iterative glycosylations. In this respect, differential reactivities of hydroxyls have been exploited for the synthesis of branched oligosaccharides by one-pot procedures 18-24 but the scope of this approach is limited because of the need of exceptional high regioselectivities. Trichloroacetimidates were selected as glycosyl donors because their activation requires only catalytic TfOH or TMSOTf. 25 Furt...