Investigation of benzoyloximes as benzoylating reagents: benzoyl-Oxyma as a selective benzoylating reagent

Abstract

Hydroxybenzotriazole (HOBt) and HOBt-derived reagents have been classified as Class I explosives, with restrictions on their transportation and storage. We explored a range of benzoylated oxime-based reagents as alternatives to benzoyloxybenzotriazole (BBTZ) for the selective benzoylation of carbohydrate polyols. Benzoylated oximes derived from 2-hydroximino-malononitrile, ethyl 2-hydroximino-2-cyanoacetate (Oxyma), and tert-butyl 2-hydroximino-2-cyanoacetate were most effective for benzoylation of a simple primary alcohol, with yields approaching that obtained for BBTZ. When applied to carbohydrate diols, the most effective reagent was identified as benzoyl-Oxyma. Benzoyl-Oxyma is a highly crystalline, readily prepared alternative to BBTZ, useful in the selective benzoylation of carbohydrate polyols.

Site-Selective Functionalization of Hydroxyl Groups in Carbohydrate Derivatives

“…Whereas benzoyl chloride (BzCl) in pyridine led to only a modest preference for acylation of the more sterically accessible 2-OH group of substrate α- 9 , a synthetically useful 2- O -acylation was achieved using benzoylimidazole in chloroform at reflux . Benzoyl cyanide (BzCN: catalytic Et 3 N, MeCN, 23 °C), benzoic anhydride (Et 3 N, CH 2 Cl 2 , room temperature) 1-(benzoyloxy)­benzotriazole (BzOBt: Et 3 N, CH 2 Cl 2 , 23 °C), and the related benzoyloxime reagent 104 (Et 3 N, CH 2 Cl 2 , 0° to 23 °C) also led to relatively high selectivities for esterification of the 2-OH group. Acylation with benzoic anhydride was dependent on the reaction conditions: the use of triethylamine as base (CH 2 Cl 2 solvent, room temperature) favored the formation of the 2- O -benzoate, but a mixture enriched in the 3- O -benzoate was generated in pyridine at 20–30 °C .…”

Metal-Involving Synthesis and Reactions of Oximes

“…O -Acyl oximes are easily accessible through well-developed syntheses utilizing oximes and (chloro)­anhydrides or carboxylic acids esters (for recent works, see refs − and refs and , respectively). Similarly, O -heteroacylations of oximes by isocyanates and isothiocyanates also proceed easily and under mild conditions (for recent works, see refs − ).…”

Synthesis of a Glycosylphosphatidylinositol (GPI) Fragment as a Potential Substrate for Mannoprotein Transglycosidases

“…There is a range of potential ways to achieve selective benzoylation of diol 6, for example, by using selective benzoylation reagents such as benzoyl cyanide, N-benzoylimidazole, or N-benzoyltetrazole, by Mitsunobu substitution reactions, or by using Benzoyl-Oxyma. 21 Our initial attempts at benzoylation were carried out by carefully controlling the reaction temperature and the number of equivalents of benzoyl chloride.…”

“…There is a range of potential ways to achieve selective benzoylation of diol 6, for example, by using selective benzoylation reagents such as benzoyl cyanide, N-benzoylimidazole, or N-benzoyltetrazole, by Mitsunobu substitution reactions, or by using Benzoyl-Oxyma. 21 Our initial attempts at benzoylation were carried out by carefully controlling the reaction temperature and the number of equivalents of benzoyl chloride. However, even at -40 °C, a close-to-equimolar mixture of the primary and secondary benzoates 7 and 8 was obtained, along with the dibenzoate 9 and unreacted starting material, indicating that the reactivity of the 2-and the 6hydroxy groups were similar under these conditions.…”