Orthoesters versus 2‐O‐Acyl Glycosides as Glycosyl Donors: Theorectical and Experimental Studies

Abstract

n-Pentenyl orthoesters (NPOEs) undergo routine acid catalyzed rearrangement into 2-O-acyl n-pentenyl glycosides (NPGs). The reactant and product can both function as glycosyl donors affording 1,2-trans linked glycosides predominantly. However, both donors differ in their rates of reactions, the yields they produce, and the nature of their byproducts, indicating that the NPOE/NPG pair may not be reacting through the same intermediates. We have therefore applied quantum chemical calculations using DFT methods and MP second order perturbation theory to learn more about orthoesters and their 2-O-acyl glycosidic counterparts. The calculations show that in the case of a manno NPG and NPOE pair, each donor goes initially to a different cationic intermediate. Thus, the former goes to a high-energy oxocarbenium ion before descending to a trioxolenium ion in which the charge is distributed over the pyrano ring oxygen, as well as the carbonyl and ether oxygen atoms of the putative C2 ester. On the other hand, ionization of the NPOE produces a dioxolenium ion lying slightly above the more stable trioxolenium counterpart. For the gluco pair, the NPG also goes to a very high-energy oxocarbenium ion, which also descends to a trioxolenium ion. However, unlike the manno analogue, the gluco NPOE does not give a dioxolenium ion; indeed, the dioxolenium is not energetically distinguishable from the trioxolenium counterpart. The theoretical observations have been tested experimentally. Thus, it was found that with manno derivatives, the orthoester is a more reactive donor than the corresponding NPG donor, whereas, for gluco derivatives, there is no advantage to using one over the other, unless one resorts to carefully selected promoters.

Methyl 1,2‐Orthoesters in Acid‐Washed Molecular Sieves Mediated Glycosylations

“…In contrast, glucosylation of diterpenoids 34 and 35 with MeOE 9 , required longer reaction times and higher amounts of AW‐MS to take place. This behavior is in agreement with a previous report on the higher reactivity of D‐mannose versus D‐glucose‐derived orthoesters (Scheme ) …”

Methyl 1,2‐Orthoesters as Useful Glycosyl Donors in Glycosylation Reactions: A Comparison with n‐Pent‐4‐enyl 1,2‐Orthoesters

“…Our explanation for the differences in regioselectivity displayed by MeOEs and NPOEs is based on the assumption of differences in the activation of NPOEs and MeOEs, as illustrated in Scheme . NPOEs are remotely activated with iodonium ion and activity is transmitted to the OR residue ( R = n ‐pent‐4‐enyl), as in furanylium ion 34 , which gives rise to dioxolenium ion 35 40. On the other hand, we postulate that acid activation of MeOEs with BF 3 · Et 2 O takes place preferentially at the glycosyl oxygen (O‐1) leading to 36 and thence 37 .…”

Some Aspects of Selectivity in the Reaction of Glycosyl Donors*

“…[21] The transition energy is seen to be higher for the disarmed species by approximately 5.6 kcal (Scheme 6). The dioxolenium ion 41 was found, but calculations also revealed a trioxolenium counterpart 40 with charge being distributed to each of the three oxygens.…”