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. 2020 Jun 5;10(11):5990-6001.
doi: 10.1021/acscatal.0c01470. Epub 2020 Apr 29.

Diastereoselective sp3 C-O Bond Formation via Visible Light-Induced, Copper-Catalyzed Cross-Couplings of Glycosyl Bromides with Aliphatic Alcohols

Fei Yu  1 , Jalen L Dickson  2 , Ravi S Loka  1 , Hengfu Xu  1 , Richard N Schaugaard  1 , H Bernhard Schlegel  1 , Long Luo  1 , Hien M Nguyen  1
Affiliations

Diastereoselective sp3 C-O Bond Formation via Visible Light-Induced, Copper-Catalyzed Cross-Couplings of Glycosyl Bromides with Aliphatic Alcohols

Fei Yu et al. ACS Catal. .

Abstract

Copper-catalyzed cross-coupling reactions have become one of the most powerful methods for generating carbon-heteroatom bonds, an important framework of many organic molecules. However, copper-catalyzed C(sp3)-O cross-coupling of alkyl halides with alkyl alcohols remains elusive because of the sluggish nature of oxidative addition to copper. To address this challenge, we have developed a catalytic copper system, which overcomes the copper oxidative addition barrier with the aid of visible light and effectively facilitates the cross-couplings of glycosyl bromides with aliphatic alcohols to afford C(sp3)-O bonds with high levels of diastereoselectivity. Importantly, this catalytic system leads to a mild and efficient method for stereoselective construction of α-1,2-cis glycosides, which are of paramount importance, but challenging. In general, stereochemical outcomes in α-1,2-cis glycosidic C-O bond-forming processes are unpredictable and dependent on the steric and electronic nature of protecting groups bound to carbohydrate coupling partners. Currently, the most reliable approaches rely on the use of a chiral auxiliary or hydrogen-bond directing group at the C2- and C4-position of carbohydrate electrophiles to control α-1,2-cis selectivity. In our approach, earth-abundant copper not only acts as a photocatalyst and a bond-forming catalyst, but also enforces the stereocontrolled formation of anomeric C-O bonds. This cross-coupling protocol enables highly diastereoselective access to a wide variety of α-1,2-cis-glycosides and biologically relevant α-glycan oligosaccharides. Our work provides a foundation for developing new methods for the stereoselective construction of natural and unnatural anomeric carbon(sp3)-heteroatom bonds.

Keywords: C(sp3)–O bond; copper catalysis; cross-coupling; stereoselective; visible light.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
(A) UV/vis absorption spectra for CuI, BPhen, and Xantphos with different mole ratios. The spectra were acquired with a 0.5 nm interval. (B) Emission spectrum of the copper complex (CuI:BPhen:Xantphos = 1:2.5:2.5) at 0.1 mM concentration with an excitation wavelength of 450 nm.
Figure 2.
Figure 2.
(a) Energy level diagram for estimating the oxidation potential of B to D from the spectroscopic measurement of the emission wavelength of B and the electrochemical measurement of the oxidation potential of the ground state A. (b) Emission spectra of [Cu(BPhen)(Xantphos)]+ (equivalent to compound I in Scheme 4) with and without MeO–, showing no noticeable difference in emission wavelength. (c) Absorption and emission spectra of compound I. (d) Cyclic voltammogram of compound I (2 mM) in acetonitrile containing 0.1 M tetrabutylammonium perchlorate as the electrolyte using GCE. Scan rate = 0.2 V.
Scheme 1.
Scheme 1.
Copper-Catalyzed C–O Bond Formation
Scheme 2.
Scheme 2.
Copper-Catalyzed Oligosaccharide Synthesis
Scheme 3.
Scheme 3.
Control Experiments
Scheme 4.
Scheme 4.
Proposed Mechanism
Scheme 5.
Scheme 5.
Summary of the Redox Potential of Excited-State Copper(I) Complex B and Substrate C (α-Glycosyl Bromide 1) Proposed in Scheme 4
See this image and copyright information in PMC

References

    1. Casitas A, Ribas X, The Role of Organometallic Copper(III) Complexes in Homogeneous Catalysis. Chem. Sci 2013, 4, 2301.
    2. Hickman AJ; Sanford MS High-Valent Organometallic Copper and Palladium in Catalysis. Nature 2012, 484, 177–185. - PMC - PubMed
    1. Beletskaya IP; Cheprakov AV Copper in Cross-Coupling Reactions: The Post-Ullmann Chemistry. Coord. Chem. Rev 2004, 248, 2337.
    2. Monnier F; Taillfer M Catalytic C-C, C-N, and C-O Ullmann-Type Coupling Reactions. Angew. Chem., Int. Ed 2009, 48, 6954. - PubMed
    1. Evano G; Blanchard N; Toumi M Copper-Mediated Coupling Reactions and Their Applications in Natural Products and Designed Biomolecules Synthesis. Chem. Rev 2008, 108, 3054. - PubMed
    2. Allen SE; Walvoord RR; Padilla-Salinas R; Kozlowski MC Aerobic Copper-Catalyzed Organic Reactions. Chem. Rev 2013, 113, 6234. - PMC - PubMed
    1. Wolter M; Nordmann G; Job GE; Buchwald SL Copper-Catalyzed Coupling of Aryl Iodides with Aliphatic Alcohols. Org. Lett 2002, 4, 973. - PubMed
    2. Altman RA; Shafir A; Choi A; Lichtor PA; Buchwald SL An Improved Cu-Based Catalyst System for the Reactions of Alcohols with Aryl Halides. J. Org. Chem 2008, 73, 284. - PubMed
    3. Liu Y; Park SK; Xiao Y; Chae J Copper(II)-Catalyzed C-O Coupling of Aryl Bromides with Aliphatic Diols: Synthesis of Ethers, Phenols, and Benzo-Fused Cyclic Ethers. Org. Biomol. Chem 2014, 12, 4747. - PubMed
    4. Zheng Y; Zou W; Luo L; Chen J; Lin S; Sun S Ligand-Free Cu-Catalyzed O-Arylation of Aliphatic Diols. RSC Adv 2015, 5, 66104.
    1. Jones GO; Liu P; Houk KN; Buchwald SL Computational Explorations of Mechanisms and Ligand-Directed Selectivities of Copper-Catalyzed Ullmann-Type Reactions. J. Am. Chem. Soc 2010, 132, 6205. - PMC - PubMed
    2. Yu H-Z; Jiang Y-Y; Fu Y; Liu L Alternative Mechanistic Explanation for Ligand-Dependent Selectivities in Copper-Catalyzed N- and O-Arylation Reactions. J. Am. Chem. Soc 2010, 132, 18078. - PubMed
    3. Giri R; Brusoe A; Troshin K; Wang JY; Font M; Hartwig JF Mechanism of the Ullman Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands: Evidence for the Reaction of Iodoarenes with Ligated Anionic CuI Intermediates. J. Am. Chem. Soc 2018, 140, 793. - PMC - PubMed

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