Stereoelectronic Factors in the Stereoselective Epoxidation of Glycals and 4-Deoxypentenosides

Abstract

Glycals and 4-deoxypentenosides (4-DPs), unsaturated pyranosides with similar structures and reactivity profiles, can exhibit a high degree of stereoselectivity upon epoxidation with dimethyldioxirane (DMDO). In most cases, the glycals and their corresponding 4-DP isosteres share the same facioselectivity, implying that the pyran substituents are largely responsible for the stereodirecting effect. Fully substituted dihydropyrans are subject to a “majority rule,” in which the epoxidation is directed toward the face opposite to two of the three groups. Removing one of the substituents has a variable effect on the epoxidation outcome, depending on its position and also on the relative stereochemistry of the remaining two groups. Overall, we observe that the greatest loss in facioselectivity for glycals and 4-DPs is caused by removal of the C3 oxygen, followed by the C5/anomeric substituent, and least of all by the C4/C2 oxygen. DFT calculations based on polarized-π frontier molecular orbital (PPFMO) theory support a stereoelectronic role for the oxygen substituents in 4-DP facioselectivity, but less clearly so in the case of glycals. We conclude that the anomeric oxygen in 4-DPs contributes toward a stereoelectronic bias in facioselectivity whereas the C5 alkoxymethyl in glycals imparts a steric bias, which at times can compete with the stereodirecting effects from the other oxygen substituents.

Regioselective and 1,2‐cis‐α‐Stereoselective Glycosylation Utilizing Glycosyl‐Acceptor‐Derived Boronic Ester Catalyst

“…[16] When the glycosylation of 11 and 32 using the boronic ester 34 was conducted, it was found that glycosylation at an axial 4-OH in 34 preferentially proceeded to give the a(1,4) glycoside 38 in 65 %y ield with high regioselectivity [a(1,4)/a(1,3) = 9.3:1] and excellent astereoselectivity (Scheme 2B). When the 1a,2aanhydrogalactose 35 [17] and 1a,2a-anhydroisomaltose 36 [8] were employed as glycosyl donors,t he glycosylations with 20 using 25 were found to proceed effectively to afford the a(1,4) glycosides 39 [18] and 40,r espectively,w ith good regio- When the 1a,2aanhydrogalactose 35 [17] and 1a,2a-anhydroisomaltose 36 [8] were employed as glycosyl donors,t he glycosylations with 20 using 25 were found to proceed effectively to afford the a(1,4) glycosides 39 [18] and 40,r espectively,w ith good regio- …”

“…Glycosylations of 11 with several 1,3-diol sugar acceptors(16)(17)(18)(19)(20)u sing the corresponding glycosyl-acceptor-derived boronic ester catalysts 21-25.Reagents and conditions: a) 1a (0.2 equiv), toluene, reflux, 3h.Bz= benzoyl. Scheme 1.…”

α-C-Glycosides via syn Opening of 1,2-Anhydro Sugars with Organozinc Compounds in Toluene/n-Dibutyl Ether

“…Even though this strategy proved to be feasible on large scale, 17 it still involves the handling and the storage of volatile peroxide and a good diastereoselectivity can be achieved in some cases only with cryogenic temperatures and extensive reaction time. 18 We were drawn to a recent report by Dondoni et al about the direct epoxidation of glycals with an in situ generated DMDO. 19 This more practical approach consists of a biphasic system (dichloromethane/water) and Oxone ® as the co-oxidant (Method B).…”

Oxidation and Reduction

“…It was concluded that the anomeric oxygen in 4-DPs contributed towards a stereoelectronic bias in facioselectivity, whereas the C(5) alkoxymethyl in glycals imparted a steric bias, which at times could compete with the stereodirecting effects from the other oxygen substituents. 301 The ab initio quantum-chemical method on the 6-31G** basis has been used to study the mechanism of selenium oxide and selenous acid oxidation of 6-methyluracil to orotic aldehyde. The mixed anhydride of acetic and selenous acids, which possessed high activity and steric accessibility in electrophilic attack on position 5 of the pyrimidine ring, was formed with a gain of energy.…”