Equatorial Anomeric Triflates from Mannuronic Acid Esters

Abstract

Activation of mannuronic acid esters leads to a conformational mixture of alpha-anomeric triflates, in which the equatorial triflate ((1)C(4) chair) is formed preferentially. This unexpected intermediate clearly opposes the anomeric effect and is mainly stabilized by the electron-withdrawing carboxylate function at C-5. Because the anomeric center carries a significant positive charge, the (1)C(4) mannopyranosyl chair approximates the favored (3)H(4) half-chair oxacarbenium ion conformation. The excellent beta-selectivity in glycosylations of mannuronates is postulated to originate from the cooperative action of the triflate counterion and the (stereo)electronic effects governing oxacarbenium ion stabilization in the transition state leading to the 1,2-cis product.

The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

“…Based on the conformational behavior of the donors and the intermediate α-triflates 18α , adopting an 1 C 4 conformation, 48,49 the high reactivity of these donors 50,51 and a large variety of glycosylation reactions, both in solution, 50,52–55 and on fluorous 56 and solid supports, 57 it has been postulated that the selectivity in these glycosylation reactions can be related to the intermediacy of an 4 H 3 oxocarbenium ion-like intermediate. 53,54,58 …”

“…This transforms all three donors into the corresponding anomeric triflates, 21–24,48,60 prior to addition of the acceptor nucleophiles. The pre-activation set-up generates a pool of reactive intermediates in the absence of the acceptor, thereby eliminating product forming pathways that originate from direct displacement reactions on the activated parent donor species.…”

Dissecting the mechanisms of a class of chemical glycosylation using primary 13C kinetic isotope effects

“…The recent demonstration of the existence of β-glycosyltriflates as stable species when the substitution pattern is favorable further supports the possibility of their intervention via a Curtin-Hammet kinetic scheme. 38 …”

Methodology Development and Physical Organic Chemistry: A Powerful Combination for the Advancement of Glycochemistry

“…It must be noted, however, that β-glycosyl triflates have been observed spectroscopically in the mannuronic acid series. 11a,51 …”