Regioselective Benzoylation of 6‐O‐Protected and 4,6‐O‐Diprotected Hexopyranosides as Promoted by Chiral and Achiral Ditertiary 1,2‐Diamines

Abstract

Monobenzoylation of triols (6‐O‐silylated glycopyranosides) or diols (4,6‐O‐benzylidenated glycopyranosides) with benzoyl chloride and triethylamine at −60° to 23° is promoted by catalytic amounts of ditertiary 1,2‐diamines. The regioselectivity depends mostly on the structure of the alcohols; it is modulated by the configuration and constitution of the diamines, as shown by comparing the effect of Oriyama's catalyst ((S)‐1 and (R)‐1), N,N,N′,N′‐tetramethylethylenediamine (TMEDA), N,N,N′,N′‐tetraethylethylenediamine (TEEDA), Et3N, and EtNMe2. The effect of the catalysts on the reactivity is impaired by their steric hindrance. In agreement with the modest enantioselectivity of the mono‐ and dibenzoylation of rac‐cyclohexane‐1,2‐diol in the presence of Oriyama's catalyst, the influence of these diamines on the regioselectivity is rather limited. While associated with procedural simplicity, these catalysts lead, in a few cases, to higher yields of a single benzoate than established methods, viz. in the preparation of the 3‐O‐benzoyl β‐D‐glucopyranoside 4, the 2‐O‐benzoyl α‐D‐galactopyranoside 22, the 3‐O‐benzoyl α‐D‐galactopyranoside 23, and the benzylidenated 2‐O‐benzoyl α‐D‐galactopyranoside 44. The regioselective benzoylation of the benzylidenated β‐D‐mannopyranoside 47, leading to 48, appears to be new.

A peptide-based catalyst approach to regioselective functionalization of carbohydrates

“…4 To date, the application of small-molecule catalysts has been fairly limited in scope, with most of the studies focused on the use of chiral nucleophilic catalysts. 5 In particular, both Yoshida 6 and Vasella 7 have made important contributions in this area, studying a set of catalysts for the selective functionalization of a range of minimally protected carbohydrate monomers. The development of a few approaches to efficient manipulation of the chiral pool could have a substantial impact, both on synthesis, and also the generation of libraries of natural products that are unambiguously 'natural-product-like' in their genesis.…”

Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules

“…Even with these successes, a major challenge in the area of site-selective catalysis is the design and application of catalysts that can overturn the inherent kinetic preference of the substrate. For most monosaccharides, an axial hydroxyl group tends to be kinetically inert, so selective modification of these groups has proven more elusive using catalyst-controlled methodologies 32 .…”

Solvent-controlled regioselective protection of allyl-4,6-benzylidene glucopyranosides

“…The acidity is modulated by intramolecular H-bonds while steric effects control the nucleophilicity. Vasella[ 7 ] and Moitessier,[ 8 ] both reported on the strength and the effects of cis- and trans-intramolecular H-bonds within protected glucose derivatives. The H-bond between the C2-hydroxyl and the α-C1-allyloxy in the partially protected glucoside 2 renders the C2-hydroxyl group the more acidic of the two free hydroxyls.…”

“…In most cases, a limiting synthetic factor is the number of functional group manipulations required to access suitable synthetic precursors. For hexopyranoses, acylation of cis-diols can be achieved with high regioselectivity either by means of metal activators such as tin, [ 1 - 3 ] silver, [ 4 ] boron[ 5 ] or copper [ 6 ] or by exploiting the relative reactivity of hydroxyl groups [ 7 , 8 ] However, metal-promoted alkylation and base-catalysed acylation of diols have proven to be highly undependable in the case of glucose and other cyclic trans-diols, where both hydroxyl groups are equatorial. For instance, reports of identical procedures describing the tin-catalysed benzylation of methyl 4,6- O -benzylidene glucopyranoside claim isolated yields ranging from the 37% and below [ 9 ] to 75% and above [ 10 ] Others reported multi-step procedures to achieve introduction of a suitable protecting group at the 2-position of the 4,6- O -benzylidene 1- O -alkyl protected glucose [ 11 ] or used enzymes to achieve selectivity[ 12 ]…”