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Palladium(II)-Catalyzed Diastereoselective 2,3-trans C(sp3)-H Arylation of Glycosides Nicolas Patrick Probst, Gwendal Grelier, Slimane Dahaoui, Mouad Alami, Vincent Gandon, and Samir Messaoudi ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b01617 • Publication Date (Web): 12 Jul 2018 Downloaded from http://pubs.acs.org on July 12, 2018
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ACS Catalysis
Palladium(II)-Catalyzed Diastereoselective 2,3-trans C(sp3)-H Arylation of Glycosides Nicolas Probst,† Gwendal Grelier,‡ Slimane Dahaoui,§ Mouâd Alami,† Vincent Gandon,¥,¶* Samir Messaoudi†,* †
BioCIS, Univ. Paris-Sud, CNRS, University Paris-Saclay, 92290, Châtenay-Malabry, France, E-mail:
[email protected] Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, 1, av. de la Terrasse, 91198 Gif-sur-Yvette (France) § Cristallographie, Résonance Magnétique et Modélisations (CRM2), UMR UL-CNRS 7036, Faculté des Sciences et Technologies, Université de Lorraine, BP 70239, Boulevard des Aiguillettes, 54506 Vandœuvre-lès-Nancy Cedex, France ¥ Laboratoire de Chimie Moléculaire (LCM), CNRS UMR 9168, Ecole Polytechnique, Université Paris-Saclay, route de Saclay, 91128 Palaiseau cedex, France ¶ Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS UMR 8182, Univ. Paris-Sud, Université Paris-Saclay, 91405 Orsay France, Email:
[email protected] ‡
ABSTRACT: We report herein the diastereoselective C(sp3)–H arylation of glycosides. A wide range of β- and α-glycosides proved able to selectively undergo Pd(II)-catalyzed coupling with diverse aryl iodides to assemble a large library of functionalized 3-arylglycosylamides. DFT calculations were performed to elucidate the unexpected trans stereoselectivity of this reaction. KEYWORDS: C(sp3)-H activation, Carbohydrate, Palladium catalysis, C-glycosides, DFT calculations. The development of stereoselective methods in which C–H bonds can be regioselectively activated and functionalized represents a major field of exploration for synthetic chemists. To overcome the issue of regiocontrol, directing groups have been developed to bring the metal close to a specific C–H bond via the formation of a suitable metallacycle. The majority of metal-catalyzed C–H functionalization reactions imply the cleavage of C(sp2)–H bonds, while C(sp3)–H activation is less described and represents a greater challenge because of the poorer reactivity of such bonds deriving from to their lower acidity.1 Given the large number and diversity of C–H bonds generally present in a molecule, a second challenge in those strategies is the control of the stereochemistry. Although the regioselective arylation of C(sp3)–H at the position of 8-aminoquinoleine used as chelating group has been largely described in the literature,2 examples occurring in a stereoselective manner are still rare. In the few reported cases, arylation of C(sp3)–H of cyclic substrates proceeds stereoselectively cis to the directing group.3 The stereoselective arylation of glycosides4 has not been achieved so far and is the subject of the work described herein (Scheme 1). The inherent complexity of carbohydrates does not facilitate C–H bond functionalization due to steric constraints and metal-complexing surrounding groups found in protected substrates.5 For the majority of them, arylglycosides are actually arylated at the anomeric position6 and can be synthesized from various cross-coupling reactions such as Negishi coupling between an arylzinc and a bromosugar,7 Stille cross-coupling with an anomeric stannane8 or a stannyl-D-glucal,9 or a D-glucal boronate,10 palladium-catalyzed ortho C–H activation,11 Heck-type reaction of a glycal and a boronic acid,12 decarboxylative coupling,13 Heck reaction of a glycal and an aryl halide.14 Very recently, Molander and co-workers reported an elegant method to synthesize non-classical arylated C-saccharides using nickel/photoredox dual catalysis.15 Although bioactive mimetics of carbohydrates could stand out from 2-aryl-glycosides, few examples of such compounds have been reported,16 and only one
Scheme 1. Concept of the stereoselective C(sp3)–H arylation of glycosides.
methodology from the Davis group17 gives access to 2-C-arylglycosides by Suzuki-Miyaura coupling of 2-iodo-glycals. Herein, we describe the stereoselective 2,3-trans -arylation of deoxyglycosides mediated by an aminoquinoline directing group. The optimization study was carried out using -glycoside 1a, having an aminoquinoline directing group, and p-iodotoluene as substrates. Details can be found in the Supporting Information (Table S1). The screening of several parameters (Pd catalyst, base, solvent, temperature, reaction time) led us to identify the best reaction conditions as the use of 20 mol% of Pd(OAc)2 and 2 equiv of Ag2CO3 in dioxane (0.1 M) at 120 °C under N2 for 48 h. With these, the desired arylated product 3-tolyl glycoside 5a could be isolated in 61% yield (Table 1, entry 1). Of note, this reaction did not work with perfluorotoluidine and aminomethylpyridine or less efficient with aminoisopropylpyridine directing groups (entries 2-4). In sharp contrast with the cisstereoselectivity observed for the seemingly related arylation of C(sp3)–H bond of simple cyclic substrates,3 5a was obtained exclusively as a 2,3-trans diastereomer. The exact structure of 5a, including its 2,3-diaxial geometry, was obtained by 1D and 2D NMR and unambiguously confirmed by crystal structure analysis (Tables 1 and Scheme 2). With the optimized conditions in hand, a library of structurally diverse 3-arylated glycosylamides 5a-p, 8b and 9d was built using electronically different sugar compounds and aryl iodides (Scheme 2). Para-substituted iodoarenes displaying electron-
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Table 1: Effect of the directing group on the arylation reactiona
Entry
Substrate
Conversion (%)b
Product
Yield (%)c
1
1a
100
5a
61
2
2
