Chemoselective Formation of Unsymmetrically Substituted Ethers from Catalytic Reductive Coupling of Aldehydes and Ketones with Alcohols in Aqueous Solution

Abstract

A well-defined cationic Ru-H complex catalyzes reductive etherification of aldehydes and ketones with alcohols. The catalytic method employs environmentally benign water as the solvent and cheaply available molecular hydrogen as the reducing agent to afford unsymmetrical ethers in a highly chemoselective manner.Etherification of oxygenated organic compounds is an ubiquitous organic transformation in both industrial and fine chemical syntheses. 1 Strong Brønsted acid and heterogeneous acid catalysts are commonly employed for industrial-scale etherification of alcohols, 2 while the Williamson ether synthesis has long been used for laboratory-scale synthesis of unsymmetrically substituted ethers. 3 Seminal catalytic C-O bond formation methods such as Ullmann-and Mitsunobu-type coupling reactions have been extensively utilized for the synthesis of aryl-substituted ethers. 4 More recently, a number of highly effective catalytic methods for unsymmetrical ethers have been developed from use of hydroalkoxylation of alkenes 5 and oxidative C-H alkoxylation of arenes. 6 The reductive etherification of carbonyl compounds has also been shown to be a synthetically powerful etherification method, but this method requires a stoichiometric amount of silane as the reducing agent. 7 Despite such remarkable progress, these catalytic etherification methods pose major synthetic and environmental problems in that they employ reactive reagents such as inorganic acids and organic alkoxide substrates, which result in the formation of copious amounts of wasteful byproducts. From the viewpoint of achieving green and sustainable catalysis, the development of an efficient and broadly applicable catalytic etherification process that NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.Organic Letters, Vol 17, No. 7 (2015): pg. 1778-1781. DOI. This article is © American Chemical Society and permission has been granted for this version to appear in e-Publications@Marquette. American Chemical Society does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from American Chemical Society. 3does not form any wasteful byproducts remains a high priority goal, particularly for the synthesis of unsymmetrically substituted ethers. 8 We recently discovered that a well-defined cationic ruthenium hydride complex [(C6H6)(PCy3)(CO)RuH] + BF4 -(1) is a highly selective catalyst precursor for the etherification of two different alcohols to form unsymmetrically substituted ethers. 9 While this etherification provides unsymmetrical ethers without forming any wasteful byproducts, it was not effective for the coupling between electronically similar or sterically demanding aliphatic alcohols, as it gave a mixture of symmetrical and unsymmetrical ethers. In an effort to extend the scope of the etherification reaction, we explored the analogous reductiv...

Auto‐Tandem Catalysis with Frustrated Lewis Pairs for Reductive Etherification of Aldehydes and Ketones

“…[8] Despite the wealth of ether linkage forming methodologies,t here is still ar oom for improvement in reaction efficiencya nd generality.R eductive etherification represents [9,10] an ideal methodology because this reaction can overcome many of the synthetic challenges of the venerable Williamson reaction [11] or acid-mediated dehydration processes. [8] Despite the wealth of ether linkage forming methodologies,t here is still ar oom for improvement in reaction efficiencya nd generality.R eductive etherification represents [9,10] an ideal methodology because this reaction can overcome many of the synthetic challenges of the venerable Williamson reaction [11] or acid-mediated dehydration processes.…”

“…[8] Despite the wealth of ether linkage forming methodologies,t here is still ar oom for improvement in reaction efficiencya nd generality.R eductive etherification represents [9,10] an ideal methodology because this reaction can overcome many of the synthetic challenges of the venerable Williamson reaction [11] or acid-mediated dehydration processes. [10] In ad ual attempt to further the evolution of the ether bond formation and the metal-free FLP hydrogenation, we sought to exploit frustrated Lewis pair catalysis for reductive etherification reaction (Scheme 1). [10] In ad ual attempt to further the evolution of the ether bond formation and the metal-free FLP hydrogenation, we sought to exploit frustrated Lewis pair catalysis for reductive etherification reaction (Scheme 1).…”

[Fp*Fc][PF6]: A remarkable non-symmetric dinuclear cation in a very stable mixed-valent state

“…[1][2] In recent years related transformations have attracted a sustained interest. [3][4][5][6][7] During these studies, [1] we also reported the ferrocenecontaining analogue 2, in which the redox-active ferrocenyl unit (Fc) was exploited to exert redoxcontrol over this catalytic transformation, [8] a topical concern in catalysis. [9][10][11] In order to explore this further, we now report the extensive characterization of the mono-oxidized derivative of 2 which is a non-symmetric Fe(II)/Fe(III) MV complex whose behavior can, as we shall see, be analyzed in the light of Hush theory.…”

Atom-Economic Synthesis of 4-Pyrones from Diynones and Water

“…Generally, water offers several "green chemistry" benefits as a solvent in organic transformations, including high efficiency, lower cost, ease of process, green and environmental protection [3,4]. Recently, there are many reports of clean transformations in water medium [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], such as coupling reactions [20][21][22][23][24][25][26][27][28][29][30], cyclizations [31][32][33][34], Michael additions [35][36][37][38][39], and condensations [40,41]. Additionally, H2O also participates in organic reactions as a nucleophile [42,43] to provide various kinds of functional compounds such as imidazo [1,2-a]pyridines [44], amino acid salts [45], α-amino ketones [46], and 1,3-oxazinan-2-ones [47]…”