Asymmetric Hydrogenation of Furans and Benzofurans with Iridium–Pyridine–Phosphinite Catalysts

Abstract

Enantioselective hydrogenation of furans and benzofurans remains a challenging task. We report the hydrogenation of 2- and 3-substituted furans by using iridium catalysts that bear bicyclic pyridine-phosphinite ligands. Excellent enantioselectivities and high conversions were obtained for monosubstituted furans with a 3-alkyl or 3-aryl group. Furans substituted at the 2-position and 2,4-disubstituted furans proved to be more difficult substrates. The best results (80-97% conversion, 65-82% enantiomeric excess) were obtained with monosubstituted 2-alkylfurans and 2-[4-(trifluoromethyl)phenyl]furan. Benzofurans with an alkyl substituent at the 2- or 3-position also gave high conversions and enantioselectivity, whereas 2-aryl derivatives showed essentially no reactivity. The asymmetric hydrogenation of a 3-methylbenzofuran derivative was used as a key step in the formal total synthesis of the cytotoxic naphthoquinone natural product (-)-thespesone.

Stereoselective Chemoenzymatic Synthesis of Optically Active Aryl-Substituted Oxygen-Containing Heterocycles

“…19 F NMR spectra were recorded by using CFCl3 as an internal standard. Absolute values of the coupling constants are reported.…”

“…Asymmetric syntheses of optically active tetrahydrofurans have also been extensively investigated in the last few decades [16] because of their presence in many natural products and biologically active compounds (e.g., Goniothalesdiol, Figure 1). The preparation of chiral tetrahydrofurans has been efficiently performed by asymmetric cycloetherifications of hydroxy olefins in the presence of organocatalysts [17] or transition metals [18], or by the catalytic asymmetric hydrogenation of substituted furans [19]. Optically active halohydrins have been successfully employed for the preparation of several chiral non-racemic oxygenated heterocycles (e.g., epoxides, oxetanes, tetrahydrofurans, pyrans).…”

Iridium‐Catalyzed Asymmetric Hydrogenation of Benzo[b]thiophene 1,1‐Dioxides

“…Following our studies of iridium N,P complexes as catalysts for the asymmetric hydrogenation of furans and benzofurans, we investigated benzothiophenes as substrates, but without success. Consequently, we decided to study benzothiophene 1,1‐dioxides as surrogates that could be converted into chiral 2,3‐dihydrobenzothiophenes by reduction of the sulfone group.…”

Selective Arene Hydrogenation for Direct Access to Saturated Carbo‐ and Heterocycles

“…[31c] Thes cope of catalyst system I includes aw ide variety of electron-poor N-heteroarenes,a nd the catalyst system can be tuned to match ap articular substrate by exploiting the facile accessibility of chiral bisphosphines.In addition to chiral bisphosphines,c hiral P, Nl igands such as phosphine-oxazolines (PHOX) have been employed in combination with iridium (II)b yt he Charette [28d] and Pfaltz groups. [32] In contrast to the (more nucleophilic) active iridium(III)-monohydride species [28e] of precatalyst I,t he active species of the iridium-PHOX catalyst system (II)i s an acidic iridium(III)-dihydride complex, [33] which is applicable to electron-poor and electron-rich N-heteroarenes as well as O-heteroarenes.Chiral ruthenium complexes can also catalyze the enantioselective hydrogenation of (hetero- )arenes.F or example,a nalogues of Noyorist ransfer hydrogenation catalyst (III)h ave been employed by the groups of Q.-H. Fana nd A. S. C. Chan, as well as others,f or the hydrogenation of arenes bearing polarized carbonylonium or iminium moieties. [34] In addition, the Kuwano group has advanced the use of combinations of the privileged transchelating chiral 2,2''-bis[1-(diphenylphosphino)ethyl]-1,1''biferrocene (PhTRAP) ligand (25)w ith ar uthenium precursor under basic conditions (IV).…”