DBN‐Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

Abstract

The 1,5‐diazabicyclo[4.3.0]non‐5‐ene (DBN)‐catalyzed regioselective acylation of carbohydrates and diols in ethyl acetate has been developed. The hydroxyl groups can be selectively acylated by the corresponding anhydride in EtOAc in the presence of a catalytic amount (as low as 0.1 equiv.) of DBN at room temperature to 40 °C. This method avoids metal catalysts and toxic solvents, which makes it comparatively green and mild, and it uses less organic base compared with other selective acylation methods. Mechanism studies indicated that DBN could catalyze the selective acylation of hydroxyl moieties through a dual H‐bonding interaction.

Size‐Induced Inversion of Selectivity in the Acylation of 1,2‐Diols

“…In kinetic resolution experiments and other 1 : 1 competition experiments it is common practice to select a single conversion point for the determination of relative reaction rates, often at conversions of around 50 %. [ 5d , 16 , 17 , 24 ] However, in order to limit the influence of the second acylation step on the ratio of the mono‐acylation, the 30 % conversion point seems more appropriate. From these measurements we derived the relative rate constant k rel,a30% defined as the ratio between the concentrations of monoesters 2b(a – g) and 3b(a – g) (Figure 2 b, for more details see Supporting Information).…”

Catalytic Approaches to Chemo- and Site-Selective Transformation of Carbohydrates

“…For substrates with an equatorial substitution at the γ-positions of the reacting hydroxy group (see the labels in 118), Ru-(PPh 3 ) 3 Cl 2 usually gave a better yield. For instance, nonprotected methyl β-D-galactopyranoside (118) was converted to the 3-O-epimerized product (148, D-gulose derivative) in 72% yield.…”

“…117 Ren, Tang, and coworkers reported that 1,5-diazabicyclo[4,3,0]non-5-ene (DBN) can catalyze regioselective acylation of carbohydrates in a similar mechanism involving bivalent hydrogen bonding between the catalyst and diols. 118 Schmidt, Peng, and co-workers focused on the cyanide ion. Cyanide ion is more basic than acetate ion, and thus, it would further increase the rate of acylation reactions (Figure 23a).…”

“…Regioselective benzoylation is also possible by using tetrabutylammonium benzoate as a catalyst . Ren, Tang, and co-workers reported that 1,5-diazabicyclo­[4,3,0]­non-5-ene (DBN) can catalyze regioselective acylation of carbohydrates in a similar mechanism involving bivalent hydrogen bonding between the catalyst and diols …”

Substrate Specific Closed-loop Optimization of Carbohydrate Protective Group Chemistry Using Bayesian Optimization and Transfer Learning

“…The regioselectivity can for instance be determined by a preference for cis-vicinal diols [16,[32][33][34] , a preference for diequatorial vicinal diols, [25] the axial oxy effect [30] the cyanide effect [13,29] , or dual hydrogen bonding. [35,36] Another aspect of the current methods is the necessity for more steps, complexations, and long reaction times at low temperatures in order to obtain acceptable selectivities. Some of the above-mentioned approaches are illustrated in Scheme 1.…”