Catalytic Site-Selective Carbamoylation of Pyranosides

Abstract

Carbamate-bearing carbohydrates contribute to the pharmacological properties of various natural glycosides. The catalytic site-selective carbamoylation of minimally protected pyranosides was achieved for the first time to bypass protection/deprotection sequences. 1-Carbamoylimidazoles were used as the carbamoylation reagents to circumvent the harmful and unstable phosgene and isocyanates. This borinic acid catalyzed transformation granted an expedient access to the tumor cell-binding carbamoylmannoside moiety of bleomycins and analogs in yields of 56% to 89%.

Site-selective carbamoylation of carbohydrates catalyzed by SnCl2/Me2SnCl2leading to complementary selectivity

“…The use of Me 2 SnCl 2 as a catalyst led to poor selectivity in Alsarraf's method (entry 14). 4 We suspected that obtaining this result is likely due to the absence of DIPEA. Without sufficient base, the cyclic intermediate between a diol and Me 2 SnCl 2 cannot be formed, resulting in the inability of Me 2 SnCl 2 to function as a catalyst.…”

“…1b). 4 Glycosides containing cis -vicinal diol were chosen as substrates and the carbamoylation followed the usual protection patterns: the equatorial hydroxyl group adjacent to the axial hydroxyl group is selectively protected. 5 This method required reflux in acetonitrile for 20–48 h, leading to 56–89% yields of carbamoylation products in 12 examples.…”

Towards better syntheses of partially methylated carbohydrates?

“…Various systems were reported during the last decade for the catalytic site-selective glycosylation, acylation, silylation, sulfonylation, benzylation, and carbamoylation 55 of unprotected carbohydrates. Organometallic (tin- 56 and iron-based 57–60 complexes), organoboron 61 (borinic 62–64 and boronic 65,66 acids), and organic 67 catalysts were involved in these transformations.…”

N-Alkyl Carbamoylimidazoles as Isocyanate Equivalents: Exploration of the Reaction Scope for the Synthesis of Ureas, Hydantoins, Carbamates, Thiocarbamates, and Oxazolidinones

“…N -Methylisocyanate equivalents are of particular importance given the considerable challenges and toxicity associated with using this reagent 2 (R 1 = Me) (Figure ). Previous studies had established N -methyl carbamoylimidazole 8a (R 1 = Me) as one such equivalent , and shown it to be a convenient, readily handled, and stable equivalent for the transfer on an N -methylcarbamoyl group. We now report a systematic study on the synthesis and use of monosubstituted carbamoylimidazoles 8 as masked isocyanates for monosubstituted carbamoyl group transfer to nucleophiles.…”