Published: February 28, 2011 r2011 American Chemical Society 3724 dx.doi.org/10.1021/ja110332r | J. Am. Chem. Soc. 2011, 133, 3724–3727 COMMUNICATION pubs.acs.org/JACS Borinic Acid-Catalyzed Regioselective Acylation of Carbohydrate Derivatives Doris Lee and Mark S. Taylor* Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada b S Supporting Information ABSTRACT: Reversible covalent interactions of organo- boron compounds are exploited as the basis for regioselec- tive borinic acid-catalyzed acylations of polyols. This catalytic protocol enables differentiation of the secondary OH groups of a wide range of carbohydrate derivatives with diverse acid chloride and chloroformate reagents, using a structurally simple diarylborinic acid-derived catalyst. T he reversible covalent interactions of organoboron com- pounds with diols have been employed extensively in the design of receptors for carbohydrates. 1 Key features of these interactions are their tolerance of aqueous medium, favorable kinetics, and selectivity for cis-vicinal diol moieties, governed by minimization of angle and torsional strain. Here, we demonstrate that such interactions may be harnessed to achieve organoboron- catalyzed monoacylations of carbohydrate derivatives with ro- bust and general regioselectivity for cis-diol motifs. This method enables the differentiation of the secondary hydroxy groups of a wide range of monosaccharide substrates by acylating agents varying significantly in steric and electronic properties, using a commercially available and inexpensive borinic ester precatalyst. The selective protection of carbohydrates has been pursued intensively for the preparation of value-added intermediates and building blocks for oligosaccharide synthesis from readily available sugar feedstocks. 2 Strategies based on catalysis are of particular interest: recent developments include enzyme-catalyzed 3 and organo- catalytic methods, 4 Lewis acid-promoted processes, 5,6 and tandem catalytic reactions of persilylated sugar derivatives. 7 Despite this progress, there remains an unmet need for catalysts displaying the combination of reliable selectivity for a given regiochemical outcome and generality for a wide range of sugar/protective group combinations. We sought to identify organoboron catalysts capable of promoting selective acylation of cis-diol moieties in carbohy- drates. Although formation of a boronate ester generally con- stitutes protection, not activation, of a diol motif, 8 Aoyama and co-workers reported that triethylamine activates fucose- and arabinose-derived boronate esters toward alkylation through a putative ate complex. 9a In a related strategy, sugar-derived boronate esters bearing a pendant hydroxy group underwent regioselective glycosylation. 10 Each of these processes required the use of a stoichiometric quantity of organoboron reagent that was initially installed in a thermally promoted condensation step, suggesting that developing catalytic reactivity of this type might be difficult. Organoboron species were evaluated as catalysts for the selective benzoylation of 1,2-cis-cyclohexanediol 1a in the pre- sence of its trans diastereomer 1b (Scheme 1). N,N-Dimethyla- minopyridine (DMAP) promoted indiscriminate acylation of 1a and 1b, as did Me 2 SnCl 2 , a known catalyst of diol acylation. 5 While boronic acids 3a-3d provided varying degrees of rate enhancement, only modest levels of selectivity for the formation of 2a were observed. 11 In contrast, the ethanolamine ester of diphenylborinic acid (4a) promoted acylation of 1a with good activity and superior selectivity. Similar results were obtained with diphenylborinic acid itself (4b), suggesting that 4a serves as a precatalyst by benzoylation and displacement of the Scheme 1. Evaluation of Catalysts for Selective Acylation of cis-Cycloalkanediols a Determined by 1 H NMR. b From ref 5a. Received: November 17, 2010