A Highly cis‐Selective and Enantioselective Metal‐Free Hydrogenation of 2,3‐Disubstituted Quinoxalines

Abstract

A wide range of 2,3-disubstituted quinoxalines have been successfully hydrogenated with H 2 using borane catalysts to produce the desired tetrahydroquinoxalines in 80-99 % yields with excellent cis selectivity. Significantly, the asymmetric reaction employing chiral borane catalysts generated by the in situ hydroboration of chiral dienes with HB(C 6 F 5 ) 2 under mild reaction conditions has also been achieved with up to 96 % ee, and represents the first catalytic asymmetric system to furnish optically active cis-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines.Tetrahydroquinoxalines are very useful moieties and present in a wide range of biologically and medicinally active compounds, and a lot of methods have been developed to access them. [1] The direct reduction of quinoxalines is one of the most efficient approaches among these methodologies. [2] In particular, the catalytic hydrogenation with H 2 as well as its asymmetric version has attracted attention and great advances have been made. [3] Since the first asymmetric hydrogenation of 2-methylquinoxaline with chiral rhodium catalysts reported by Murata and co-workers in 1987, [4a] a variety of chiral transition metal catalysts have been developed for the enantioselective hydrogenation of 2-substituted quinoxalines. [4] However, in sharp contrast, the reduction of 2,3substituted quinoxalines has been rarely reported. [5,6] For example, Deselms and Mosher reported a noncatalytic lithium aluminium hydride reduction of 2,3-dimethylquinoxaline to give a cis product in 1960 (Scheme 1). [5a] Gavin and coworkers described the reduction of 2,3-dimethyl-and 2,3diphenylquinoxaline with borane in THF solution (Scheme 1). [5b] Recently, Xu, Fan, and Xiao reported an iridiumcatalyzed transfer cis-selective hydrogenation of 2,3-dimethylquinoxaline (Scheme 1). [5c] Glorius and co-workers described a ruthenium/carbene-catalyzed cis-selective hydrogenation of 2,3-diphenyl-6-methylquinoxaline. In 2011, Fan and co-workers disclosed the first and the only asymmetric hydrogenation of 2,3-dialkylquinoxalines with chiral cationic ruthenium diamine catalysts to give the desired trans products with up to 99 % ee and 86:14 d.r. (Scheme 1). [5e] Therefore, the development of highly stereoselective hydrogenations of 2,3disubstituted quinoxalines under mild reaction conditions with a good substrate scope, especially the corresponding asymmetric reactions, still remains a challenge in the field of catalytic hydrogenation.The recently emerging frustrated Lewis pair (FLP) chemistry provides a breakthrough approach for metal-free hydrogenation with molecular H 2 since catalytic hydrogenation has long been dominated by transition-metal catalysis. [7][8][9] A wide range of unsaturated compounds have proven to be effective substrates for the FLP-catalyzed hydrogenations. [9,10] Significantly, some promising advances have also been made for FLP-catalyzed asymmetric reactions, [11,12] but the asymmetric hydrogenation of silyl enol ethers is the only example to proceed with more than 90 % ee. ...

Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

“…Synthesis and Characterization of Iridium(III) Complex Dye: The dye was synthesized by using a previously reported protocol. 4′-methyl-[2,2′-bipyridine]-4-carbaldehyde [44] and the auxiliary ligand 2-methyl-3phenylquinoxaline (mpq) [45] were synthesized according to literature methods. The iridium(III) dimmer [Ir(mpq) 2 Cl] 2 [46] was synthesized by using the similar method of [Ir(ppy) 2 13 13 C NMR spectra were recorded using a Bruker 500 nuclear magnetic resonance spectrometer using CDCl 3 or CD 3 OD as the deuterated solvent.…”

Spiro‐Bicyclic Bisborane Catalysts for Metal‐Free Chemoselective and Enantioselective Hydrogenation of Quinolines

“…[11] These catalysts are highly effective and selective in asymmetric imine hydrogenations.W eattempted to use them for the hydrogenation of 2-methylquinoline,aless bulky substrate that was not studied by either Repo [8] or Du. [9,10] Disappointingly,w eo bserved no reaction (Scheme 1a). We hypothesized that our catalysts were not sterically hindered enough to prevent the coordination of this quinoline to the boron center.T oi ncrease the steric bulk, we intended to change the fused bicyclic structure to as piro-bicyclic structure because the latter consists of two perpendicular rings,w hich produce as teric environment similar to that in Scheme 1.…”

Asymmetric Catalysis with Chiral Frustrated Lewis Pairs

“…Interestingly, Du and coworkers found that using catalytic amount of B(C 6 F 5 ) 3 (10 mol%) or B( p ‐HC 6 F 4 ) 3 (5 mol%) as a catalyst, the hydrogenation of 2,3‐disubstituted quinoxalines proceeded smoothly to afford a variety of tetrahydroquinoxalines in 80%—99% yields with excellent cis ‐selectivity. Significantly, the asymmetric reaction employing chiral borane catalyst generated by the in situ hydroboration of chiral diene 15b with HB(C 6 F 5 ) 2 has been successfully achieved to give the desired product in high yields with high levels of cis ‐selectivities and enantioselectivities (Scheme ) . However, 2,3‐dialkyl‐ or diarylquinoxalines stayed inert for this catalytic asymmetric reaction.…”