Formal Glycosylation of Quinones with exo-Glycals Enabled by Iron-Mediated Oxidative Radical–Polar Crossover

Abstract

The intermolecular C–O coupling reaction of 1,4-quinones with exo-glycals under iron hydride hydrogen atom transfer (HAT) conditions is described. This method provides a direct and regioselective access to a wide range of phenolic O-ketosides related to biologically relevant natural products in diastereomeric ratios up to >98:2 in the furanose and pyranose series. No trace of the corresponding C-glycosylated products that might have resulted from the radical alkylation of 1,4-quinones was observed. The results of mechanistic experiments suggest that the key C–O bond-forming event proceeds through an oxidative radical–polar crossover process involving a single-electron transfer between the HAT-generated glycosyl radical and the electron-acceptor quinone.

From Sweet Molecular Giants to Square Sugars and Vice Versa

“…[146][147][148][149] Mechanistic studies indicated that the initially formed glycosyl pseudoanomeric radical could be oxidized to give the corresponding glycosyl oxocarbenium ion intermediate through the formation of a charge-transfer complex involving the electron-acceptor quinone (Scheme 18a). 150 This oxidative radical-polar crossover process was supported by several observations as mentioned above, and also by control experiments. The best evidence supporting the cationic scenario came from competition experiments using an equimolar amount of a quinone and of acrylonitrile, employed as a radical-trapping agent (Scheme 18b).…”

A Fries-Type Rearrangement Strategy for the Construction of Stereodefined Quaternary Pseudoanomeric Centers: An Entry into C-Naphthyl Ketosides

“…R f 0.49 (cyclohexane/EtOAc: 3/1); 1 H NMR (400 MHz, CDCl 3 ) δ 9.32 (s, 1H), 8.38 (dd, J = 6.6, 3.2 Hz, 1H), 8.07 (dd, J = 6.3, 3.3 Hz, 1H), 7.53 (d, J = 3.3 Hz, 1H), 7.51 (d, J = 3.3 Hz, 1H), 7.49–6.99 (m, 20H), 6.72 (s, 1H), 4.98 (d, J = 11.1 Hz, 1H), 4.92–4.86 (m, 2H), 4.83 (s, 1H), 4.70 (d, J = 12.0 Hz, 1H), 4.55–4.45 (m, 3H), 4.10 (t, J = 9.5 Hz, 1H), 3.95 (d, J = 9.7 Hz, 1H), 3.92–3.81 (m, 3H), 3.73 (d, J = 10.4 Hz, 1H), 3.68 (dd, J = 10.0, 2.4 Hz, 1H), and 1.72 (s, 3H). The analysis is consistent with the experimental data reported in the literature …”

“…R f 0.45 (cyclohexane/EtOAc: 5/1); 1 H NMR (400 MHz, CDCl 3 ) δ 9.32 (s, 1H), 8.41–8.36 (m, 1H), 8.20–8.14 (m, 1H), 7.57–7.47 (m, 4H), 7.45–7.38 (m, 2H), 7.37–7.27 (m, 9H), 7.24–7.16 (m, 5H), 7.05–6.98 (m, 2H), 6.67 (s, 1H), 4.98 (d, J = 11.2 Hz, 1H), 4.91 (d, J = 11.2 Hz, 1H), 4.90 (d, J = 10.8 Hz, 1H), 4.72 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 11.0 Hz, 1H), 4.53 (d, J = 12.1 Hz, 1H), 4.52 (d, J = 10.6 Hz, 1H), 4.16–4.09 (m, 1H), 4.00 (d, J = 9.8 Hz, 1H), 3.97–3.90 (m, 2H), 3.89–3.84 (m, 1H), 3.77 (s, 3H), 3.75–3.67 (m, 2H), and 1.82 (s, 3H). The analysis is consistent with the experimental data reported in the literature …”

“…To do so, the HAT-mediated formal glycosylation has to be followed by a O - → C -glycoside rearrangement process, offering the attractive possibility of direct access to either the O -aryl ketosides or to the corresponding bis- C , C -aryl glycosides from exo -glycals in either one or two steps, respectively (Scheme ). Precedent for such an aryl migration that is mechanistically related to the Fries rearrangements exists and has been described for the synthesis of classical C -glycosides via Friedel–Crafts reactions involving aldosyl oxocarbenium ion intermediates. , However, to our knowledge, there were no examples of the use of the so-called Suzuki rearrangement for the construction of quaternary pseudoanomeric or anomeric centers in C -aryl ketosides when we initiated our study . Herein, we describe that C -naphthyl ketosides can be synthesized with high diastereoselectivity through BF 3 ·OEt 2 -catalyzed, Fries-type rearrangement.…”

Remote Radical 1,3-, 1,4-, 1,5-, 1,6- and 1,7-Difunctionalization Reactions

“…In addition to traditional homolytic bond cleavage-based radical reactions induced by radical initiators or photolysis [ 15 , 16 , 17 ], other methods such as single electron transfer reagents [ 18 , 19 , 20 , 21 , 22 ], catalytic photoredox [ 23 , 24 , 25 , 26 , 27 , 28 ], and electrochemical reactions [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ] have been developed and are gaining increasing popularity. For the remote 1,3-, 1,4-, 1,5-, 1,6- and 1,7-difunctionalization reactions presented in this paper, the initial addition of the radical X is followed by radical rearrangement through resonance, hydrogen atom transfer (HAT), group transfer, or opening of strained-rings to relocate the position of the radical.…”