A Mechanistic Probe into 1,2-cis Glycoside Formation Catalyzed by Phenanthroline and Further Expansion of Scope.
Adv Synth Catal
; 363(16): 4054-4066, 2021 Aug 13.
Article
em En
| MEDLINE
| ID: mdl-35431716
ABSTRACT
Phenanthroline, a rigid and planar compound with two fused pyridine rings, has been used as a powerful ligand for metals and a binding agent for DNA/RNA. We discovered that phenanthroline could be used as a nucleophilic catalyst to efficiently access high yielding and diastereoselective α-1,2-cis glycosides through the coupling of hydroxyl acceptors with α-glycosyl bromide donors. We have conducted an extensive investigation into the reaction mechanism, wherein the two glycosyl phenanthrolinium ion intermediates, a 4C1 chair-liked ß-conformer and a B2,5 boat-like α-conformer, have been detected in a ratio of 21 (ßα) using variable temperature NMR experiments. Furthermore, NMR studies illustrate that a hydrogen bonding is formed between the second nitrogen atom of phenanthroline and the C1-anomeric hydrogen of sugar moiety to stabilize the phenanthrolinium ion intermediates. To obtain high α-1,2-cis stereoselectivity, a Curtin-Hammett scenario was proposed wherein interconversion of the 4C1 chair-like ß-conformer and B2,5 boat-like α-conformer is more rapid than nucleophilic addition. Hydroxyl attack takes place from the α-face of the more reactive 4C1 ß-phenanthrolinium intermediate to give an α-anomeric product. The utility of the phenanthroline catalysis is expanded to sterically hindered hydroxyl nucleophiles and chemoselective coupling of an alkyl hydroxyl group in the presence of a free C1-hemiacetal. In addition, the phenanthroline-based catalyst has a pronounced effect on site-selective couplings of triol motifs and orthogonally activates the anomeric bromide leaving group over the anomeric fluoride and sulfide counterparts.
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01-internacional
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MEDLINE
Idioma:
En
Revista:
Adv Synth Catal
Ano de publicação:
2021
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Article