Chemoselective conversion of biologically sourced polyols into chiral synthons

Abstract

Crude oil currently provides much of the world's energy, but it is also the source of many feedstock chemicals. Methodology for the conversion of biomass into useful chemicals has often focused on either complete deoxygenation or the production of high-volume platform chemicals. Here, we describe the chemoselective partial reduction of silyl-protected C6O6-derived polyols to produce a diverse set of oxygen-functionalized chiral synthons. The combination of B(C6F5)3 and a tertiary silane efficiently generates a reactive equivalent of an electrophilic silylium ion (R3Si(+)) and a hydride (H(-)) reducing agent. The mechanism of oxygen loss does not involve a dehydrative elimination and thus avoids ablation of stereochemistry. Neighbouring group participation and the formation of cyclic intermediates is key to achieving selectivity in these reactions and, where both primary and secondary C-O bonds are present, the mechanism allows further control. The method provides--in one or two synthetic steps--highly improved syntheses of many C6On synthons as well as several previously undescribed products.

Modulating Electrostatic Interactions in Ion Pair Intermediates To Alter Site Selectivity in the C−O Deoxygenation of Sugars

“…Our synthetic and mechanistic experiments on complex sugars are consistent with the Piers mechanism, [1,2,5] wherein BCF activates the silane via an h 1 -adduct, which is in turn heterolytically and reversibly cleaved by an oxygenated nucleophile (the sugar) to yield a cationic silyloxonium ion that is paired with the H-BCF À anion/reductant. [10][11][12][13][14][15][16] According to the calculations of Sakata and Fujimoto, [17] these contact ion pairs are dynamic and multiple orientations (local minima) can be sampled prior to the rate-determining C À O reduction.…”

Borane catalysed ring opening and closing cascades of furans leading to silicon functionalized synthetic intermediates

“…The relative stereochemistry ( anti -) of two substituents in the resultant cyclopropane product can be reasoned by proposing a nucleophilic substitution of an in situ generated oxonium species VI (ref. 20) by the borohydride nucleophile to minimize the steric repulsion between substituents33.…”

“…For instance, Gagné et al . found that B(C 6 F 5 ) 3 catalyses the deoxygenation of carbohydrate-based polyols with hydrosilanes to give chiral-alcohol synthons19 or hydrocarbons2021 with remarkable chemoselectivity. Njardarson et al .…”

Transformation of Sugars into Chiral Polyols over a Heterogeneous Catalyst

“…De novo synthesis is also proposed as an alternative method for the synthesis of deoxy sugars, but suffers from multistep synthesis, low yield, and low availability of starting materials. Recently, Gagné and co‐workers demonstrated an effective method for selective breaking of C−O bonds in silyl‐protected polyols, using B(C 6 F 5 ) 3 and a tertiary silane, to deliver chiral polyol synthons while maintaining the stereocenters of polyols . However, the method required silyl protection of the OH groups and more than an equivalent amount of silane additives.…”