Highly enantioselective hydrogenation of various N-Boc-indoles proceeded successfully in the presence of the ruthenium complex generated from an appropriate ruthenium precursor and a trans-chelate chiral bisphosphine PhTRAP. Various 2- or 3-substituted indoles were converted into chiral indolines with high enantiomeric excesses (up to 95% ee). The PhTRAP-ruthenium catalyst was able to promote the hydrogenation of 2,3-dimethylindoles, giving cis-2,3-dimethylindolines with 72% ee.

Catalytic asymmetric hydrogenation of N-Boc-protected pyrroles proceeded with high enantioselectivity by using a ruthenium catalyst modified with a trans-chelating chiral bisphosphine PhTRAP. The ruthenium catalyst prepared from Ru(eta3-methallyl)2(cod) and (S,S)-(R,R)-PhTRAP in the presence of triethylamine was the most enantioselective for the asymmetric hydrogenation of methyl pyrrole-2-carboxylate, giving the desired (S)-proline derivative with 79% ee in 92% yield. Moreover, 2,3,5-trisubstituted pyrroles bearing a large substituent at the 5-position were hydrogenated with 93-99.7% ee. The asymmetric reduction of 4,5-dimethylpyrrole-2-carboxylate gave only all-cis isomer and created three chiral centers with high degree of stereocontrol in a single process. This is the first highly enantioselective reduction of pyrroles.

Vanishing aromaticity: A chiral ruthenium complex catalyzes the hydrogenation of 2,6‐ or 2,7‐disubstituted naphthalenes to give chiral tetralins with up to 92 % ee. The chiral catalyst is applicable to the regio‐ and enantioselective reduction of 6‐substituted 2‐alkoxynaphthalenes and preferentially hydrogenates the alkoxy‐substituted arene rings.

No abstract

Various bisindolylmaleimides have fluorescence emission maxima wavelengths longer than 500 nm, large Stokes shifts longer than 200 nm, different fluorescence emission wavelengths at an excitation wavelength of 365 nm, and a long-lasting chemiluminescence. The expansion of the pi-conjugation, the pi-bond electronic structure, and oxidation of the C=C bond at the 2,3-position of the maleimide moiety are crucial for producing these fluorescence and chemiluminescence properties.

Indole derivatives R 0140Ruthenium-Catalyzed Asymmetric Hydrogenation of N-Boc-Indoles. -An efficient ruthenium catalyst allows the highly enantioselective hydrogenation of various N-Boc-protected indoles and 2,3-disubstituted indoles. -(KUWANO*, R.; KASHIWABARA, M.; Org. Lett. 8 (2006) 12, 2653-2655; Dep. Chem., Fac. Sci., Kyushu Univ., Higashi, Fukuoka 812, Japan; Eng.) -R. Steudel 41-105

The catalytic asymmetric hydrogenation of heteroarenes has been intensively studied during the last decade. [1] Nowadays, various heteroaromatics, for example, indoles, [2] pyrroles, [3] and quinolines, [4] can be reduced to the corresponding chiral heterocycles with high stereoselectivity through asymmetric catalysis. [5][6][7][8] Glorius and co-workers recently found that a chiral N-heterocyclic carbene-ruthenium catalyst allowed the site-selective hydrogenation of the carbocyclic rings of some quinoxalines, producing chiral 5,6,7,8-tetrahydroquinoxalines with up to 88 % ee. [9][10][11] However, to the best of our knowledge, the catalytic asymmetric hydrogenation of aromatics containing no heteroatoms remains unexplored. [12,13] Herein, we report the first successful enantioselective hydrogenation of carbocyclic arenes, naphthalenes, through asymmetric catalysis.Previously, we had developed the highly enantioselective hydrogenation of N-Boc indoles with a ruthenium catalyst generated from [{RuCl 2 (p-cymene)} 2 ] and the chiral bisphosphine ligand, PhTrap. [2d, 14] During the course of this study, we attempted the reduction of 2-naphthylindole 1 with the PhTrap-ruthenium catalyst (Scheme 1). To our surprise, none of the expected product 2 was obtained. The hydro-genation was accompanied by the partial reduction of the naphthalene ring, yielding tetrahydronaphthylindoline 3 with 90 % ee. This observation suggested that the ruthenium complex was capable of reducing carbocyclic aromatic rings. In this context, we began to study the catalytic asymmetric hydrogenation of naphthalenes.In our initial attempt, a solution of dimethyl naphthalene-2,6-dicarboxylate (4 a) in 1,4-dioxane was stirred at 60 8C under hydrogen gas (50 atm) in the presence of [RuCl-(p-cymene){(S,S)-(R,R)-PhTrap}]Cl (6) [2d] catalyst. Although formation of the hydrogenation product 5 a was observed, the desired reaction was very sluggish and the enantiomeric excess of 5 a was only 22 % ee (Table 1, entry 1). Both the stereoselectivity and the reaction rate were affected by the ester substituents of the naphthalene substrate. The reaction of ethyl ester 4 b also proceeded in low yield, but the ethyl substituent brought about a remarkable improvement in the stereoselectivity (entry 2). The use of 4 c, which is a larger and more flexible ester, resulted in a moderate yield of chiral tetralin 5 c (entry 3). The enantiomeric excess of 5 c was improved to 78 % ee by conducting the hydrogenation at lower temperature (entry 4). The enantioselectivity scarcely Scheme 1. Asymmetric hydrogenation of 2-naphthylindole. Boc = tertbutoxycarbonyl. Table 1: Catalytic asymmetric hydrogenation of naphthalene-2,6-dicarboxylate 4. [a] Entry R (4) Additive Solvent Conv. [%] [b] ee [%] [c]

Supporting InformationGeneral and Materials. All NMR spectra were measured with Bruker AVANCE 400 (9.4 T magnet) spectrometer. In 1 H NMR spectra, chemical shifts (ppm) referenced to internal tetramethylsilane (0.00 ppm, in CDCl 3 ) or residual solvent (7.15 ppm, in C 6 D 6 ). In 13 C NMR spectra, chemical shifts (ppm) referenced to the carbon signal of the deuterated solvents (77.0 ppm in CDCl 3 or 128.0 ppm in C 6 D 6 ). IR spectra were measured with JASCO FT/IR-4100. Elemental and high resolution mass (HRMS) analyses were performed by Service Centre of Elementary Analysis of Organic Compounds and Institute for Materials Chemistry and Engineering (ICME) in Kyushu University, respectively.Flash column chromatographies and medium-pressure liquid chromatographies (MPLC) were performed with silica gel 60 (230-400 mesh, Merck) and C.I.G. pre-packed column CPS-223L-1 (Kusano, Tokyo, Japan), respectively.Acetonitrile (MeCN), ethyl acetate (EtOAc), 2-propanol (i-PrOH), and triethylamine (Et 3 N) were dried with calcium hydride. Methanol (MeOH) was dried with Mg(OMe) 2 . These solvents and reagents were distilled under nitrogen atmosphere. Tetrahydrofuran (THF) (HPLC grade, without inhibitor) was deoxidized by purging with nitrogen for 30 min and was dried with an alumina column system (GlassContour Co.). Ru(η 3 -methallyl) 2 (cod), 1 (S,S)-(R,R)-PhTRAP, 2 Methyl N-(tert-butoxycarbonyl)pyrrole-2-carboxylate (1a), 3 were prepared according to literature procedures. All other materials were purchased and used without further purification. Preparations of N-Boc Pyrroles 1. General Procedure of N-Boc Protection of Pyrroles.Under nitrogen atmosphere, (Boc) 2 O (2.40 g, 11 mmol) was added to a solution of a pyrrole (10 mmol) and DMAP (61 mg, 0.5 mmol) in dry MeCN (3.3 ml) at room temperature. The mixture was stirred until the pyrrole disappeared completely or the reaction mixture ceased evolving carbon dioxide (monitored by a bubbler tube). After water was added, the resulting mixture was extracted with EtOAc. The organic phase was washed with brine, dried with Na 2 SO 4 , and evaporated under reduced pressure. The residue was purified with a flash column chromatography (EtOAc/hexane) to give the desired N-Boc-pyrroles 1. S2Methyl N-(tert-Butoxycarbonyl)-3,5-dimethylpyrrole-2-carboxylate (1b). N MeO 2 C Me Me Boc 1bThe general procedure was followed with use of methyl 3,5-dimethylpyrrole-2-carboxylate 4 (1.25 g, 8.2 mmol). The reaction was conducted for 17 h. The crude product was purified with a flash column chromatography (EtOAc/hexane = 1/10) to give 1b (1.47 g, 71% yield) as pale yellow oil: 1