Synthesis of Electronically Deficient Atropisomeric Bisphosphine Ligands and Their Application in Asymmetric Hydrogenation of Quinolines

Abstract

A series of electronically deficient atropisomeric bisphos­phine ligands have been synthesized from (S)-MeO-BiPhep. The introduction­ of electron-withdrawing groups in the ligands had a dramatic influence on both the enantioselectivity and the activity of catalyst. The iridium complex of the MeO-BiPhep-based ligand bearing a trifluoromethanesulfonyl group was successfully applied in the asymmetric hydrogenation of quinolines with ee values of up to 95% and turnover numbers (TON) of up to 14,600.

The direct asymmetric hydrogenation of quinoline derivatives provides a convenient route to chiral tetrahydroquinolines, which are useful intermediates and building blocks for the construction of a variety of alkaloids and biologically­ active compounds. [¹] Since our group’s pioneering work on the asymmetric hydrogenation of quinolines using the iridium/bisphosphine/iodine catalyst system with high enantioselectivities and yields, [²] exciting advances have been achieved in this field. [³-7] Most effort has focused on developing effective ligands for higher enantioselectivity and catalytic activity, especially the latter. Thus far, several bisphosphine ligands with high catalytic activity have been developed with the iridium-catalyzed system. Fan and co-workers employed BINAP-cored dendrimers as ligands in iridium-catalyzed asymmetric hydrogenation of quinolines with turnover numbers (TON) up to 43,000. [8] The authors proposed that the formation of inactive species was reduced by the encapsulation of the iridium complex into a dendrimer framework and, thus, the activity of the catalyst was enhanced. Very recently, our group also found that the introduction of bulky groups on the coordination phosphorous atoms of P,P- and P,N-ligands could improve the catalytic activity with a substrate-to-catalyst (S/C) ratio of up to 25,000 and ee values up to 93%. [9] For the above work, the steric hindrance of the matrix ligands were modified to improve their activities. Furthermore, the electronic properties of the ligands were also investigated. In 2007, Lemaire and co-workers synthesized several electronically enriched chiral BINAP derivatives and applied them in the iridium-catalyzed asymmetric hydrogenation of quinolines, however, the enantioselectivity and activity were unsatisfactory. [¹0] Recently, Xu et al. found that air-stable, electro­ni­-cally deficient P-Phos and DifluorPhos showed high activity in the hydrogenation of quinolines with TON up to 43,000. [¹¹]

Encouraged by the above results, we envisioned that the catalytic activity might be improved by introducing electron-withdrawing substituents to the backbone of atrop­isomeric bisphosphine ligands. Commercially available MeO-BiPhep (L1) was thought to be a suitable candidate because of its readily modifiable substituents at the 6- and 6′-positions of the biaryl backbone. Hence, this compound was chosen as the starting material to synthesize electronically deficient atropisomeric bisphosphine ligands (Scheme  [¹] ).

These ligands were easily obtained through condensation of (S)-OH-BiPhep with the corresponding acyl chloride or PhNTf₂ (Scheme  [²] ) with 45-89% yields. [¹²]

With these electronically deficient ligands in hand, iridium-catalyzed asymmetric hydrogenation of quinolines was investigated. Initially, 2-methylquinoline was chosen as a model substrate and the catalysts were prepared in situ from [Ir(cod)Cl]₂ and the ligands in tetrahydrofuran. The hydrogenation reaction was run on a S/C molar ratio of 1000, with molecular iodine (0.5 mol%) as additive; the results are summarized in Table  [¹] . After 22 hours, full conversions were obtained for all ligands. The lowest ee value was obtained (entry 1; 78%) for the matrix ligand MeO-BiPhep (L1), which was also lower than that obtained with a catalyst loading of 100 (78 vs 94% ee). [²] Gratifyingly, the enantioselectivity was enhanced dramatically with the introduction of electron-withdrawing ester groups on the ligand (entries 2-7). For the commercially available ligand L2a, with a cyclohexanecarbonyl instead of a methyl group, 86% ee was obtained (entry 2). When more electron-withdrawing aroyl groups were introduced, the enantioselectivities were further increased (entries 3-6; 89-91% ee). It is noteworthy that the highest enantioselectivity was achieved for L3, with an electron-withdrawing trifluoromethanesulfonyl group (entry 7; 95% ee), which was consistent with our initial expectation. Based on the above results, it was clear that the ligands with electronically deficient substituents showed excellent performance in iridium-catalyzed asymmetric hydrogenation of 2-methylquinoline, with high enantioselectivity and activity being achieved.

Table 1 Asymmetric Hydrogenation of 2-Methylquinoline^a

Entry	Ligand	Yield (%)b	ee (%)c
1	L1	98	78 (S)
2	L2a	98	86 (S)
3	L2b	99	90 (S)
4	L2c	98	91 (S)
5	L2d	98	89 (S)
6	L2e	98	91 (S)
7	L3	99	95 (S)
a Reaction conditions: 1a (1 mmol), [Ir(cod)Cl]2 (0.0005 mmol), ligand (0.0011 mmol), I2 (0.0050 mmol), THF (2 mL), r.t., 22 h. b Isolated yield. c Determined by HPLC analysis.

With these promising results in hand, the effect of solvent, amount of iodine, hydrogen pressure, and temperature on the activity and enantioselectivity was further studied using iridium complexes of L3 as the catalyst; the results are summarized in Table  [²] . Solvent screening trials indicated that the reaction was strongly solvent-dependent. The use of toluene and benzene gave similar enantioselectivities to those achieved with tetrahydrofuran, but gave lower yields (entries 2 and 3). The use of dichloromethane and 2-propanol resulted in much lower yields and enantioselectivities (entries 4 and 5). Slightly lower yield and enantioselectivity were obtained in ethyl acetate (entry 6). Ethereal solvents were more effective than other solvents (entries 1 and 7), and the highest enantioselectivity was obtained in tetrahydrofuran (entry 1; 95%). Thus, tetrahydrofuran was the best choice in terms of both yield and enantioselectivity.

It was noticed that the catalytic performance was also related to the amount of additive iodine. In the absence of iodine, very low yield and enantioselectivity were observed (entry 11). Increasing the amount of iodine to 1 mol%, or decreasing the amount to 0.25 mol% had no obvious effect on either the yield or enantioselectivity (entries 8 and 9), but the ee value decreased significantly with 0.125 mol% iodine (entry 10). Either reducing the pressure or increasing the temperature gave full conversions but slightly lower enantioselectivities (entries 12 and 13). Thus, the optimized reaction conditions were: [Ir(cod)Cl]₂, L3, and iodine (0.5 mol%) in tetrahydrofuran under a hydrogen atmosphere (700 psi) at room temperature.

Table 2 Optimization of Reaction Conditions^a

Entry	Solvent	I2 (mol%)	Yield (%)b	ee (%)c
1	THF	0.5	99	95 (S)
2	toluene	0.5	19	94 (S)
3	benzene	0.5	46	93 (S)
4	CH2Cl2	0.5	10	71 (S)
5	i-PrOH	0.5	15	41 (S)
6	EtOAc	0.5	91	90 (S)
7	dioxane	0.5	98	94 (S)
8	THF	1.0	98	95 (S)
9	THF	0.25	98	94 (S)
10	THF	0.125	97	91 (S)
11	THF	-	19	6 (S)
12d	THF	0.5	99	94 (S)
13e	THF	0.5	99	93 (S)
a Reaction conditions: 1a (1 mmol), [Ir(cod)Cl]2 (0.0005 mmol), L3 (0.0011 mmol), H2 (700 psi), solvent (2 mL), r.t., 22 h. b Isolated yield. c Determined by HPLC analysis. d H2 (300 psi), r.t. e H2 (700 psi), 50 ˚C.

Having established the optimal conditions, a variety of 2-substituted quinoline derivatives were tested to explore the scope of the reaction. As summarized in Table  [³] , several 2-alkyl substituted quinolines were hydrogenated with high yields and excellent enantioselectivities, regardless of the length of side chain (entries 1-5; >93% ee). Remarkably, the carbon-carbon double bond in the side chain of the substrate was also hydrogenated (entry 4). Slightly lower enantioselectivity was obtained with hydroxyl groups on the side chain (entry 6). It was noted that excellent yields and good enantioselectivities were also observed for 2-arylethyl substituted quinolines (entries 7 and 8). For substrates possessing a substituent on the 6-position, the yields were also excellent, but slightly lower enantioselectivities were observed (entries 9 and 10). Moreover, it was found that the presence of an electron-withdrawing group at the 6-position of the substrate gave better results than those with an electron-donating substituent (92 versus 87% ee). The yield was also excellent with 2-aryl-substituted quinoline, but the enantioselectivity was only moderate (entry 11).

Table 3 Asymmetric Hydrogenation of Quinoline Derivatives^a

Entry	R¹	R²	Product	Yield (%)b	ee (%)c
1	H	Me	2a	99	95 (S)
2	H	Et	2b	93	95 (S)
3	H	n-Pr	2c	97	94 (S)
4	H	3-butenyl	2d	95	94 (S)
5	H	n-pentyl	2e	98	94 (S)
6	H	Me2C(OH)CH2-	2f	99	87 (R)
7	H	3,4-(MeO)2C6H3(CH2)2-	2g	99	93 (S)
8	H	3-BnO-4-MeOC6H3(CH2)2-	2h	96	93 (S)
9	Me	Me	2i	96	87 (S)
10	F	Me	2j	97	92 (S)
11	H	Ph	2k	95	60 (R)
a Reaction conditions: 1 (1 mmol), [Ir(cod)Cl]2 (0.0005 mmol), L3 (0.0011 mmol), I2 (0.0050 mmol), H2 (700 psi), THF (2 mL), r.t., 22 h. b Isolated yield. c Determined by HPLC analysis.

To further evaluate the catalytic efficiency of the [Ir(cod)Cl]₂, L3, and iodine system in asymmetric hydrogenation, the effect of the S/C molar ratio on the conversion and enantioselectivity of this reaction was investigated. 2-Methylquinoline was selected as substrate and the results are shown in Table  [4] .

Table 4 Effect of S/C Ratio on the Conversion and Enantioselectivity^a

S/C	1000	5000d	10000d,e	20000d,e
Conv. (%)b	>95	>95	>95	73
Ee (%)c	95	95	95	95
a Reaction conditions: 1a (1 mmol), [Ir(cod)Cl]2/L3 (0.5/1.1), I2 (0.0050 mmol), H2 (700 psi), THF (2 mL), r.t., 22 h. b Determined by ¹H NMR analysis. c Determined by HPLC analysis. d I2 (0.0100 mmol) was used. e Reaction time: 36 h.

It was notable that the enantioselectivity remained unchanged (95% ee) when the S/C ratio was increased. When the S/C ratio was raised to 5000:1, the reaction proceeded smoothly with complete conversion. When the S/C ratio was increased to 10000:1, prolonging the reaction time could facilitate the reaction to full conversion. However, when the S/C ratio was increased to 20000:1, the conversion decreased to 73%.

In conclusion, a series of electronically deficient atropisomeric bisphosphine ligands were conveniently synthesized and successfully applied in the asymmetric hydrogenation of quinoline derivatives; up to 95% ee was obtained and TON reached 14,600. More importantly, we have shown that the introduction of electron-withdrawing groups to (S)-MeO-BiPhep had a dramatic effect on the enantioselectivity and the activity of catalyst. Our future work will focus on designing other ligands and extending the catalytic system to other hydrogenation reactions.

All reactions were performed under N₂ in dried flasks using Schlenk techniques. Commercially available reagents were used without further purification. Solvents were dried and distilled under N₂ before use. ^¹H, ^¹³C and ^³¹P NMR spectra were recorded at r.t. in CDCl₃ with a 400 MHz Bruker DRX-400 spectrometer. Enantiomeric excesses were determined by HPLC analysis with an Agilent 1100 instrument fitted with a chiral column as described below. Optical rotations were measured with a JASCO P-1010 polarimeter. All reactions were monitored by TLC analysis. Flash column chromatography was performed on either silica gel (particle size 200-300 mesh) or Al₂O₃ gel (particle size 200-300 mesh).

Bisphosphine Ligands ( S )-L2a-e; General Procedure A [¹²a]

Under an N₂ atmosphere, to a solution of (S)-OH-BiPhep [4f] (1.0 equiv) in anhydrous CH₂Cl₂ (10 mL), was added t-BuOK (2.4 equiv) and the mixture was stirred at r.t. for 30 min. Acyl chloride a-e (2.4 equiv) was added and the solution was stirred at r.t. for an additional 2 h. Degassed H₂O (10 mL) was added, the organic layer separated, and the aqueous layer was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by either recrystallization or column chromatography.

( S )-6,6′-Bis(diphenylphosphino)-1,1′-biphenyl-2,2′-diylbis(cyclohexanecarboxylate) (L2a) [¹³]

Obtained following General Procedure A, with (S)-OH-BiPhep (83 mg, 0.15 mmol), t-BuOK (40 mg, 0.36 mmol), and cyclohexanecarbonyl chloride a (53 mg, 0.36 mmol). The crude product was purified by column chromatography on silica gel (PE-EtOAc, 30:1→25:1) to give compound L2a.

Yield: 67 mg (58%); white solid; mp 234-235 ˚C; R _f = 0.82 (PE-EtOAc, 5:1); [α] _d ^²³ -92.2 (c 0.67, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.42-7.23 (m, 12 H), 7.15-7.23 (m, 6 H), 7.03-7.14 (m, 8 H), 1.77-1.94 (m, 2 H), 1.18-1.69 (m, 10 H), 0.93-1.18 (m, 9 H), 0.74-0.93 (m, 1 H).

( S )-6,6′-Bis(diphenylphosphino)-1,1′-biphenyl-2,2′-diylbis(benzenecarboxylate) (L2b)

Obtained following General Procedure A, with (S)-OH-BiPhep (110 mg, 0.20 mmol), t-BuOK (54 mg, 0.48 mmol), and benzoyl chloride b (68 mg, 0.48 mmol). The crude product was purified by recrystallization (CH₂Cl₂-n-hexane) to give compound L2b.

Yield: 97 mg (64%); white solid; mp 195-196 ˚C; R _f = 0.64 (PE-EtOAc, 5:1); [α] _d ^²³ -38.6 (c 0.70, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.41-7.53 (m, 6 H), 7.33-7.40 (m, 4 H), 7.10-7.30 (m, 22 H), 7.03 (t, J = 7.3 Hz, 4 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 163.9, 149.4, 149.3, 140.4, 138.4, 138.3, 136.2, 136.1, 134.8, 134.7, 134.6, 133.3, 133.2, 133.1, 131.7, 130.3, 129.6, 129.0, 128.9, 128.5, 128.4, 128.2, 128.1, 123.0.

^³¹P NMR (162 MHz, CDCl₃): δ = -15.28 (s).

HRMS: m/z [M + Na]⁺ calcd for C₅₀H₃₆O₄P₂Na: 785.1987; found: 785.1988.

( S )-6,6′-Bis(diphenylphosphino)-1,1′-biphenyl-2,2′-diylbis(4-methoxybenzenecarboxylate) (L2c)

Obtained following General Procedure A, with (S)-OH-BiPhep (110 mg, 0.20 mmol) and t-BuOK (54 mg, 0.48 mmol), and 4-methoxybenzoyl chloride c (82 mg, 0.48 mmol). The crude product was purified by column chromatography on Al₂O₃ gel (PE-EtOAc, 10:1→5:1) to give L2c.

Yield: 74 mg (45%); white solid; mp 161-162 ˚C; R _f = 0.36 (PE-EtOAc, 5:1); [α] _d ^²³ -8.0 (c 0.67, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, J = 8.8 Hz, 4 H), 7.35 (d, J = 4.4 Hz, 4 H), 7.15-7.31 (m, 16 H), 7.09-7.15 (m, 2 H), 7.05 (t, J = 7.4 Hz, 4 H), 6.73 (d, J = 8.9 Hz, 4 H), 3.81 (s, 6 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 163.6, 149.4, 134.8, 134.7, 134.6, 133.3, 133.2, 133.1, 132.4, 131.5, 128.9, 128.4, 128.1, 123.0, 122.1, 113.5, 55.6.

^³¹P NMR (162 MHz, CDCl₃): δ = -15.23 (s).

HRMS: m/z [M + Na]⁺ calcd for C₅₂H₄₀O₆P₂Na: 845.2198; found: 845.2175.

( S )-6,6′-Bis(diphenylphosphino)-1,1′-biphenyl-2,2′-diylbis(3,5-bistrifluoromethylbenzenecarboxylate) (L2d)

Obtained following General Procedure A, with (S)-OH-BiPhep (110 mg, 0.20 mmol), t-BuOK (54 mg, 0.48 mmol), and 3,5-bis(trifluoromethyl)benzoyl chloride d (133 mg, 0.48 mmol). The crude product was purified by column chromatography on silica gel (PE-EtOAc, 50:1→30:1) to give L2d.

Yield: 185 mg (89%); white solid; mp 76-77 ˚C; R _f = 0.82 (PE-EtOAc, 5:1); [α] _d ^²³ -11.8 (c 0.70, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.96 (s, 2 H), 7.76 (s, 4 H), 7.37-7.53 (m, 4 H), 7.24-7.34 (m, 12 H), 7.16-7.23 (m, 4 H), 7.08 (t, J = 7.4 Hz, 2 H), 6.97 (t, J = 7.5 Hz, 4 H).

^¹³C NMR (101 MHz, CDCl₃): δ = 161.2, 148.8, 148.7, 141.4, 141.3, 137.9, 137.8, 137.7, 135.2, 135.1, 135.0, 133.9, 133.7, 133.5, 133.0, 132.9, 132.8, 132.5, 132.2, 132.1, 131.8, 131.6, 131.5, 130.3, 129.5, 129.4, 128.6, 128.5, 128.4, 126.7, 126.6, 124.3, 122.4, 121.6.

^³¹P NMR (162 MHz, CDCl₃): δ = -15.00 (s).

HRMS: m/z [M + Na]⁺ calcd for C₅₄H₃₂F₁₂O₄P₂Na: 1057.1482; found: 1057.1479.

( S )-6,6′-Bis(diphenylphosphino)-1,1′-biphenyl-2,2′-diylbis(2,3,4,5,6-pentafluorobenzenecarboxylate) (L2e)

Obtained following General Procedure A, with (S)-OH-BiPhep (110 mg, 0.20 mmol), t-BuOK (54 mg, 0.48 mmol), and 2,3,4,5,6-pentafluorobenzoyl chloride e (111 mg, 0.48 mmol). The crude product was purified by column chromatography on silica gel (PE-EtOAc, 50:1→30:1) to give L2e.

Yield: 157 mg (83%); white solid; mp 68-69 ˚C; R _f = 0.76 (PE-EtOAc, 5:1); [α] _d ^²³ -86.4 (c 0.73, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.44 (t, J = 7.9 Hz, 2 H), 7.19-7.31 (m, 14 H), 7.12-7.19 (m, 6 H), 7.09 (t, J = 7.4 Hz, 4 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 156.7, 148.7, 148.6, 146.8, 146.7, 146.6, 144.9, 144.8, 144.7, 144.3, 144.2, 144.0, 142.4, 142.2, 142.0, 141.3, 141.2, 139.0, 138.8, 138.7, 137.7, 137.6, 136.5, 136.3, 136.2, 136.0, 135.9, 135.2, 135.0, 134.9, 134.8, 134.6, 134.3, 134.1, 133.9, 133.2, 133.1, 133.0, 132.8, 129.5, 128.9, 128.5, 128.3, 128.1, 128.0, 122.8.

^³¹P NMR (162 MHz, CDCl₃): δ = -14.84 (s).

HRMS: m/z [M + H]⁺ calcd for C₅₀H₂₆F₁₀O₄P₂: 943.1225; found: 943.1248.

( S )-6,6′-Bis(diphenylphosphino)-1,1′-biphenyl-2,2′-diylbis(tri­fluoromethylsulfonate) (L3) [¹²b]

To a suspension of NaH (60% in mineral oil, 10 mg, 0.24 mmol) in THF (7 mL) under argon, was carefully added a solution of (S)-OH-BiPhep (55 mg, 0.10 mmol) in THF (8 mL) at 0 ˚C, and the resulting mixture was stirred at r.t. for 30 min. After cooling to 0 ˚C, PhNTf₂ (86 mg, 0.24 mmol) was added and the mixture was stirred at r.t. for an additional 2 h. The mixture was cooled to 0 ˚C and degassed H₂O (10 mL) was added. The resulting mixture was diluted with CH₂Cl₂ (40 mL) and the organic layer was washed with degassed H₂O (10 mL) and brine (10 mL), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (PE-EtOAc, 20:1→10:1) to give L3.

Yield: 71 mg (87%); white solid; mp 159-160 ˚C; R _f  = 0.70 (PE-EtOAc, 5:1); [α] _d ^²³ +12.2 (c 0.97, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.44 (t, J = 8.0 Hz, 2 H), 7.25-7.36 (m, 8 H), 7.14-7.25 (m, 12 H), 6.98-7.07 (m, 4 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 148.7, 148.6, 142.5, 142.4, 136.7, 136.6, 136.5, 135.2, 135.1, 134.7, 134.5, 134.4, 134.3, 134.1, 133.7, 133.5, 133.4, 133.3, 133.1, 132.9, 130.7, 129.4, 128.8, 128.6, 120.6, 119.9, 116.7.

^³¹P NMR (162 MHz, CDCl₃): δ = -14.47 (s).

HRMS: m/z [M + Na]⁺ calcd for C₃₈H₂₆F₆O₆P₂S₂Na: 841.0448; found: 841.0454.

Iridium-Catalyzed Asymmetric Hydrogenation of Quinoline Derivatives: General Procedure B

A mixture of [Ir(cod)Cl]₂ (1.0 mg, 0.0015 mmol) and L3 (2.7 mg, 0.0033 mmol) in THF (3.0 mL) was stirred at r.t. for 10 min in a glovebox. I₂ (1.3 mg, 0.0050 mmol) and substrate (1.0 mmol) in THF (1.0 mL) were placed in a stainless steel autoclave and the catalyst solution (1.0 mL) was added by using a syringe. The hydrogenation was performed at r.t. under H₂ (700 psi) for 22 h. After carefully releasing the hydrogen, the reaction mixture was concentrated to afford the crude product. Purification was performed by silica gel column chromatography (PE-EtOAc) to give the pure product. The enantiomeric excesses were determined by chiral HPLC with chiral columns (OJ-H, OD-H, or AS-H).

( S )-2-Methyl-1,2,3,4-tetrahydroquinoline (2a) [²]

Yield: 99%; yellow oil; 95% ee; [α] _d ^²² -82.8 (c 0.87, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 6.95-7.04 (m, 2 H), 6.59-6.70 (m, 1 H), 6.45-6.56 (m, 1 H), 3.68 (br, 1 H), 3.29-3.51 (m, 1 H), 2.82-2.94 (m, 1 H), 2.70-2.84 (m, 1 H), 1.91-2.01 (t, J = 12.3 Hz, 1 H), 1.54-1.69 (t, J = 21.4 Hz, 1 H), 1.24 (dd, J = 6.2, 3.0 Hz, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 145.0, 129.4, 126.9, 121.3, 117.1, 114.2, 47.3, 30.3, 26.8, 22.8.

HPLC (OJ-H; n-hexane-i-PrOH, 95:5; 254 nm; 0.8 mL/min): t _R = 13.8 [(S) major], 15.4 [(R) minor] min.

( S )-2-Ethyl-1,2,3,4-tetrahydroquinoline (2b) [²]

Yield: 93%; yellow oil; 95% ee; [α] _d ^²³ -83.1 (c 1.00, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.00 (t, J = 7.2 Hz, 2 H), 6.63 (t, J = 7.3 Hz, 1 H), 6.51 (d, J = 8.0 Hz, 1 H), 3.80 (br, 1 H), 3.13-3.26 (m, 1 H), 2.66-2.96 (m, 2 H), 1.90-2.13 (m, 1 H), 1.47-1.76 (m, 3 H), 1.03 (t, J = 7.4 Hz, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 144.9, 129.4, 126.9, 121.6, 117.0, 114.2, 53.2, 29.6, 27.8, 26.6, 10.2.

HPLC (OJ-H; n-hexane-i-PrOH, 90:10; 254 nm; 0.8 mL/min): t _R = 9.8 [(S) major], 10.8 [(R) minor] min.

( S )-2-Propyl-1,2,3,4-tetrahydroquinoline (2c) [²]

Yield: 97%; yellow oil; 94% ee; [α] _d ^²³ -72.6 (c 0.70, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.00 (t, J = 7.2 Hz, 2 H), 6.63 (t, J = 7.3 Hz, 1 H), 6.50 (d, J = 8.4 Hz, 1 H), 3.78 (br, 1 H), 3.23-3.33 (m, 1 H), 2.58-2.99 (m, 2 H), 1.94-2.04 (m, 1 H), 1.57-1.70 (m, 1 H), 1.38-1.56 (m, 4 H), 0.89-1.12 (m, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 144.9, 129.4, 126.9, 121.5, 117.0, 114.2, 51.5, 39.1, 28.3, 26.6, 19.1, 14.4.

HPLC (OJ-H; n-hexane-i-PrOH, 90:10; 254 nm; 0.8 mL/min): t _R = 9.1 [(S) major], 11.2 [(R) minor] min.

( S )-2-Butyl-1,2,3,4-tetrahydroquinoline (2d) [²]

Yield: 95%; yellow oil; 94% ee; [α] _d ^²² -82.8 (c 1.07, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 6.97 (t, J = 7.3 Hz, 2 H), 6.61 (t, J = 7.3 Hz, 1 H), 6.49 (d, J = 8.2 Hz, 1 H), 3.78 (br, 1 H), 3.12-3.43 (m, 1 H), 2.61-2.99 (m, 2 H), 1.88-2.12 (m, 1 H), 1.56-1.68 (m, 1 H), 1.46-1.55 (m, 2 H), 1.26-1.45 (m, 4 H), 0.92-0.99 (m, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 144.9, 129.4, 126.9, 121.6, 117.1, 114.2, 51.8, 36.6, 28.3, 28.1, 26.6, 23.0, 14.3.

HPLC (OJ-H; n-hexane-i-PrOH, 90:10; 254 nm; 0.8 mL/min): t _R = 8.1 [(S) major], 9.3 [(R) minor] min.

( S )-2-Pentyl-1,2,3,4-tetrahydroquinoline (2e) [²]

Yield: 98%; yellow oil; 94% ee; [α] _d ^²³ -75.1 (c 0.73, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.00 (t, J = 7.5 Hz, 2 H), 6.65 (t, J = 7.4 Hz, 1 H), 6.57 (d, J = 7.8 Hz, 1 H), 4.26 (br, 1 H), 3.23-3.33 (m, 1 H), 2.71-2.89 (m, 2 H), 1.90-2.05 (m, 1 H), 1.24-1.72 (m, 9 H), 0.94 (t, J = 6.7 Hz, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 144.2, 129.5, 126.9, 122.0, 117.7, 114.7, 52.0, 36.6, 32.1, 28.1, 26.5, 25.6, 22.8, 14.3.

HPLC (OJ-H; n-hexane-i-PrOH, 90:10; 254 nm; 0.8 mL/min): t _R = 7.4 [(S) major], 8.0 [(R) minor] min.

( R )-2-Methyl-1-(1,2,3,4-tetrahydroquinolin-2-yl)propan-2-ol (2f) [²]

Yield: 99%; white solid; 87% ee; [α] _d ^²³ -52.0 (c 0.70, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 6.96 (t, J = 7.7 Hz, 2 H), 6.59 (t, J = 7.3 Hz, 1 H), 6.49 (d, J = 7.9 Hz, 1 H), 3.51-3.63 (m, 1 H), 2.82-2.95 (m, 1 H), 2.67-2.79 (m, 1 H), 1.80-1.90 (m, 1 H), 1.55-1.77 (m, 3 H), 1.32 (d, J = 5.2 Hz, 6 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 129.4, 126.9, 121.1, 116.9, 114.6, 72.2, 49.0, 48.6, 33.0, 30.0, 28.0, 26.8.

HPLC (OD-H; n-hexane-i-PrOH, 90:10; 254 nm; 0.8 mL/min): t _R = 8.1 [(S) minor], 9.4 [(R) major] min.

( S )-2-(3′,4′-Dimethoxyphenethyl)-1,2,3,4-tetrahydroquinoline (2g) [²]

Yield: 99%; yellow oil; 93% ee; [α] _d ^²³ -75.3 (c 0.73, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 6.93-7.02 (m, 2 H), 6.80-6.84 (m, 1 H), 6.73-6.79 (m, 2 H), 6.62 (t, J = 7.3 Hz, 1 H), 6.46 (d, J = 8.1 Hz, 1 H), 3.89 (s, 3 H), 3.88 (s, 3 H), 3.79 (br, 1 H), 3.29-3.35 (m, 1 H), 2.74-2.89 (m, 2 H), 2.66-2.74 (m, 2 H), 1.95-2.06 (m, 1 H), 1.77-1.88 (m, 2 H), 1.61-1.76 (m, 1 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 149.1, 147.4, 144.7, 134.6, 129.4, 126.9, 121.5, 120.3, 117.2, 114.3, 111.8, 111.4, 56.1, 56.0, 51.4, 38.6, 32.0, 28.2, 26.4.

HPLC (AS-H; n-hexane-i-PrOH, 95:5; 254 nm; 0.8 mL/min): t _R = 14.5 [(R) minor], 15.4 [(S) major] min.

( S )-2-(3′-Benzyloxy-4′-methoxyphenethyl)-1,2,3,4-tetrahydroquinoline (2h) [4b]

Yield: 96%; yellow oil; 93% ee; [α] _d ^²³ -49.2 (c 0.80, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.42-7.47 (m, 2 H), 7.33-7.39 (m, 2 H), 7.27-7.32 (m, 1 H), 6.92-7.00 (m, 2 H), 6.83 (d, J = 8.5 Hz, 1 H), 6.73-6.79 (m, 2 H), 6.60 (t, J = 7.2 Hz, 1 H), 6.44 (d, J = 7.8 Hz, 1 H), 5.15 (s, 2 H), 3.88 (s, 3 H), 3.71 (br, 1 H), 3.14-3.28 (m, 1 H), 2.67-2.84 (m, 2 H), 2.60-2.67 (m, 2 H), 1.89-2.00 (m, 1 H), 1.71-1.80 (m, 2 H), 1.53-1.70 (m, 1 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 148.2, 148.1, 144.6, 137.3, 134.4, 129.3, 128.6, 127.9, 127.4, 126.8, 121.3, 121.0, 117.1, 114.7, 114.2, 112.1, 71.1, 56.2, 51.0, 38.3, 31.7, 28.0, 26.3.

HPLC (AS-H; n-hexane-i-PrOH, 97:3; 254 nm; 0.5 mL/min): t _R = 30.1 [(R) minor], 32.2 [(S) major] min.

( S )-2,6-Dimethyl-1,2,3,4-tetrahydroquinoline (2i) [²]

Yield: 96%; yellow solid; 87% ee; [α] _d ^²² -68.1 (c 0.73, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 6.79-6.81 (m, 2 H), 6.43 (d, J = 7.9 Hz, 1 H), 3.58 (br, 1 H), 3.32-3.43 (m, 1 H), 2.78-2.90 (m, 1 H), 2.66-2.76 (m, 1 H), 2.23 (s, 3 H), 1.88-1.98 (m, 1 H), 1.53-1.66 (m, 1 H), 1.22 (d, J = 6.3 Hz, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 142.6, 130.0, 127.4, 126.4, 121.4, 114.4, 47.5, 30.5, 26.8, 22.8, 20.6.

HPLC (OJ-H; n-hexane-i-PrOH, 90:10; 254 nm; 0.8 mL/min): t _R = 13.5 [(S) major], 16.7 [(R) minor] min.

( S )-6-Fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (2j) [²]

Yield: 97%; yellow solid; 92% ee; [α] _d ^²³ -80.7 (c 0.73, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 6.65-6.72 (m, 2 H), 6.36-6.44 (m, 1 H), 3.57 (br, 1 H), 3.30-3.40 (m, 1 H), 2.77-2.90 (m, 1 H), 2.66-2.75 (m, 1 H), 1.89-1.97 (m, 1 H), 1.51-1.63 (m, 1 H), 1.21 (d, J = 6.3 Hz, 3 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 156.8, 154.5, 141.2, 122.7, 122.6, 115.7, 115.5, 114.9, 114.8, 113.4, 113.2, 47.5, 30.1, 26.9, 22.7.

HPLC (OD-H; n-hexane-i-PrOH, 95:5; 254 nm; 0.8 mL/min): t _R = 6.8 [(R) minor], 8.1 [(S) major] min.

( R )-2-Phenyl-1,2,3,4-tetrahydroquinoline (2k) [6a]

Yield: 95%; yellow solid; 60% ee; [α] _d ^²³ +19.1 (c 1.00, CHCl₃).

^¹H NMR (400 MHz, CDCl₃): δ = 7.28-7.49 (m, 5 H), 6.97-7.10 (m, 2 H), 6.69 (t, J = 7.3 Hz, 1 H), 6.57 (d, J = 7.9 Hz, 1 H), 4.47 (dd, J = 9.3, 2.9 Hz, 1 H), 4.06 (br, 1 H), 2.89-3.02 (m, 1 H), 2.71-2.84 (m, 1 H), 2.10-2.22 (m, 1 H), 1.96-2.09 (m, 1 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 145.0, 144.9, 129.5, 128.8, 127.6, 127.1, 126.7, 121.0, 117.3, 114.1, 56.4, 31.2, 26.6.

HPLC (AS-H; n-hexane-i-PrOH, 95:5; 254 nm; 0.8 mL/min): t _R = 7.1 [(R) major], 21.5 [(S) minor] min.

Acknowledgment

We are grateful for financial support from the National Science Foundation of China (21032003 & 20921092), the National Basic Research Program (2010CB833300) and the Chinese Academy of Sciences.

References

• 1a Keay JG. In Comprehensive Organic Synthesis   Vol. 8:  Pergamon; Oxford: 1991.  p.579 
  Search in Google Scholar
• 1b Katrizky AR. Rachwal S. Bachwal B. Tetrahedron  1996,  52:  15031 
  Search in Google Scholar
• 1c Barton DH. Nakanishi K. Meth-Cohn O. In Comprehensive Natural Products Chemistry   Vol. 1-9:  Elsevier; Oxford: 1999. 
  Search in Google Scholar
• 2 Wang W.-B. Lu S.-M. Yang P.-Y. Han X.-W. Zhou Y.-G. J. Am. Chem. Soc.  2003,  125:  10536 
  CrossrefSearch in Google Scholar
• For recent reviews on hydrogenation of heteroaromatic compounds, see:
• 3a Dyson PJ. Dalton Trans.  2003,  2964 
• 3b Glorius F. Org. Biomol. Chem.  2005,  3:  4171 
  Search in Google Scholar
• 3c Lu S.-M. Han X.-W. Zhou Y.-G. Chin. J. Org. Chem.  2005,  25:  634 
  Search in Google Scholar
• 3d Zhou Y.-G. Acc. Chem. Res.  2007,  40:  1357 
  Search in Google Scholar
• 3e Kuwano R. Heterocycles  2008,  76:  909 
  Search in Google Scholar
• For our group’s work on the asymmetric hydrogenation of quinolines, see:
• 4a Lu S.-M. Han X.-W. Zhou Y.-G. Adv. Synth. Catal.  2004,  346:  909 
  Search in Google Scholar
• 4b Yang P.-Y. Zhou Y.-G. Tetrahedron: Asymmetry  2004,  15:  1145 
  Search in Google Scholar
• 4c Zhao Y.-J. Wang Y.-Q. Zhou Y.-G. Chin. J. Catal.  2005,  26:  737 
  Search in Google Scholar
• 4d Lu S.-M. Wang Y.-Q. Han X.-W. Zhou Y.-G. Angew. Chem. Int. Ed.  2006,  45:  2260 
  Search in Google Scholar
• 4e Wang D.-W. Zeng W. Zhou Y.-G. Tetrahedron: Asymmetry  2007,  18:  1103 
  Search in Google Scholar
• 4f Wang X.-B. Zhou Y.-G. J. Org. Chem.  2008,  73:  5640 
  Search in Google Scholar
• 4g Wang D.-W. Wang X.-B. Wang D.-S. Lu S.-M. Zhou Y.-G. Li Y.-X. J. Org. Chem.  2009,  74:  2780 
  Search in Google Scholar
• 4h Wang D.-W. Wang D.-S. Chen Q.-A. Zhou Y.-G. Chem. Eur. J.  2010,  16:  1133 
  Search in Google Scholar
• 4i Wang D.-S. Zhou Y.-G. Tetrahedron Lett.  2010,  51:  3014 
  Search in Google Scholar
• For other groups’ work on metal-catalyzed asymmetric hydrogenation of quinolines, see:
• 5a Fache F. Synlett  2004,  2827 
• 5b Fujita K.-I. Kitatsuji C. Furukawa S. Yamaguchi R. Tetrahedron Lett.  2004,  45:  3215 
  Search in Google Scholar
• 5c Xu L.-J. Lam K.-H. Ji J.-X. Wu J. Fan Q.-H. Lo W.-H. Chan ASC. Chem. Commun.  2005,  1390 
• 5d Lam K.-H. Xu L.-J. Feng L.-C. Fan Q.-H. Lam F.-L. Lo W.-H. Chan ASC. Adv. Synth. Catal.  2005,  347:  1755 
  Search in Google Scholar
• 5e Wu J. Chan ASC. Acc. Chem. Res.  2006,  39:  711 
  Search in Google Scholar
• 5f Reetz MT. Li X.-G. Chem. Commun.  2006,  2159 
• 5g Qiu L. Kwong FY. Wu J. Lam WH. Chan S. Yu W.-Y. Li Y.-M. Guo R. Zhou Z. Chan ASC. J. Am. Chem. Soc.  2006,  128:  5955 
  Search in Google Scholar
• 5h Yamagata T. Tadaoka H. Nagata M. Hirao T. Kataoka Y. Ratovelomanana-Vidal V. Genet JP. Mashima K. Organometallics  2006,  25:  2505 
  Search in Google Scholar
• 5i Chan S.-H. Lam K.-H. Li Y.-M. Xu L.-J. Tang W.-J. Lam F.-L. Lo W.-H. Yu W.-Y. Fan Q.-H. Chan ASC. Tetrahedron: Asymmetry  2007,  18:  2625 
  Search in Google Scholar
• 5j Deport C. Buchotte M. Abecassis K. Tadaoka H. Ayad T. Ohshima T. Genet J.-P. Mashima K. Ratovelomanana-Vidal V. Synlett  2007,  2743 
• 5k Li Z.-W. Wang T.-L. He Y.-M. Wang Z.-J. Fan Q.-H. Pan J. Xu L.-J. Org. Lett.  2008,  10:  5265 
  Search in Google Scholar
• 5l Zhou H.-F. Li Z.-W. Wang Z.-J. Wang T.-L. Xu L.-J. He Y.-M. Fan Q.-H. Pan J. Gu L.-Q. Chan ASC. Angew. Chem. Int. Ed.  2008,  47:  8464 
  Search in Google Scholar
• 5m Lu S.-M. Bolm C. Adv. Synth. Catal.  2008,  350:  1101 
  Search in Google Scholar
• 5n Mršić N. Lefort L. Boogers JAF. Minnaard AJ. Feringa BL. de Vries JG. Adv. Synth. Catal.  2008,  350:  1081 
  Search in Google Scholar
• 5o Eggenstein M. Thomas A. Theuerkauf J. Franciò G. Leitner W. Adv. Synth. Catal.  2009,  351:  725 
  Search in Google Scholar
• 5p Wang C. Li C.-Q. Wu X.-F. Pettman A. Xiao J.-L. Angew. Chem. Int. Ed.  2009,  48:  6524 
  Search in Google Scholar
• 5q Tadaoka H. Cartigny D. Nagano T. Gosavi T. Ayad T. Genet J.-P. Ohshima T. Ratovelomanana-Vidal V. Mashima K. Chem. Eur. J.  2009,  15:  9990 
  Search in Google Scholar
• 5r Wang Z.-J. Zhou H.-F. Wang T.-L. He Y.-M. Fan Q.-H. Green Chem.  2009,  11:  767 
  Search in Google Scholar
• 5s Parekh V. Ramsden JA. Wills M. Tetrahedron: Asymmetry  2010,  21:  1549 
  Search in Google Scholar
• 5t Gou F.-R. Li W. Zhang XM. Liang Y.-M. Adv. Synth. Catal.  2010,  352:  2441 
  Search in Google Scholar
• For the work on organocatalytic asymmetric hydrogenation of quinolines, see:
• 6a Rueping M. Antonchick AP. Theissmann T. Angew. Chem. Int. Ed.  2006,  45:  3683 
  Search in Google Scholar
• 6b Rueping M. Theissmann T. Raja S. Bats JWP. Adv. Synth. Catal.  2008,  350:  1001 
  Search in Google Scholar
• 6c Guo Q.-S. Du D.-M. Xu J. Angew. Chem. Int. Ed.  2008,  47:  759 
  Search in Google Scholar
• For selected examples on asymmetric hydrogenation of other heteroaromatic compounds, see, for quinoxalines:
• 7a Cobley CJ. Henschke JP. Adv. Synth. Catal.  2003,  345:  195 
  Search in Google Scholar
• 7b Mršić N. Jerphagnon T. Minnaard AJ. Feringa BL. de Vries JG. Adv. Synth. Catal.  2009,  351:  2549 
  Search in Google Scholar
• 7c Tang W.-J. Xu L.-J. Fan Q.-H. Wang J. Fan B.-M. Zhou Z.-Y. Lam K.-H. Chan ASC. Angew. Chem. Int. Ed.  2009,  48:  9135 
  Search in Google Scholar
• 7d Cartigny D. Nagano T. Ayad T. Genet JP. Ohshima T. Mashima K. Ratovelomanana-Vidal V. Adv. Synth. Catal.  2010,  352:  1886 
  Search in Google Scholar
• For furans, see:
• 7e Ohta T. Miyake T. Seido N. Kumobayashi H. Takaya H. J. Org. Chem.  1995,  60:  357 
  Search in Google Scholar
• 7f Kaiser S. Smidt SP. Pfaltz A. Angew. Chem. Int. Ed.  2006,  45:  5194 
  Search in Google Scholar
• 7g Feiertag P. Albert M. Nettekoven U. Spindler F. Org. Lett.  2006,  8:  4133 
  Search in Google Scholar
• For pyridines, see:
• 7h Raynor SA. Thomas JM. Raja R. Johnson BFG. Belle RG. Mantle MD. Chem. Commun.  2000,  1925 
• 7i Glorius F. Spielkamp N. Holle S. Goddard R. Lehmann CW. Angew. Chem. Int. Ed.  2004,  43:  2850 
  Search in Google Scholar
• 7j Legault CY. Charette AB. J. Am. Chem. Soc.  2005,  127:  8966 
  Search in Google Scholar
• 7k Wang X.-B. Zeng W. Zhou Y.-G. Tetrahedron Lett.  2008,  49:  4922 
  Search in Google Scholar
• For indoles, see:
• 7l Kuwano R. Sato K. Kurokawa T. Karube D. Ito Y. J. Am. Chem. Soc.  2000,  122:  7614 
  Search in Google Scholar
• 7m Kuwano R. Kaneda K. Ito T. Sato K. Kurokawa T. Ito Y. Org. Lett.  2004,  6:  2213 
  Search in Google Scholar
• 7n Kuwano R. Kashiwabara M. Org. Lett.  2006,  8:  2653 
  Search in Google Scholar
• 7o Baeza A. Pfaltz A. Chem. Eur. J.  2010,  16:  2036 
  Search in Google Scholar
• 7p Wang D.-S. Chen Q.-A. Li W. Yu C.-B. Zhou Y.-G. Zhang XM. J. Am. Chem. Soc.  2010,  132:  8909 
  Search in Google Scholar
• For pyrroles, see:
• 7q Kuwano R. Kashiwabara M. Ohsumi M. Kusano H. J. Am. Chem. Soc.  2008,  130:  808 
  Search in Google Scholar
• 8 Wang Z.-J. Deng G.-J. Li Y. He Y.-M. Tang W.-J. Fan Q.-H. Org. Lett.  2007,  9:  1243 
  CrossrefSearch in Google Scholar
• 9 Wang D.-S. Zhou J. Wang D.-W. Guo Y.-L. Zhou Y.-G. Tetrahedron Lett.  2010,  51:  525 
  CrossrefSearch in Google Scholar
• 10 Jahjah M. Alame M. Pellet-Rostaing S. Lemaire M. Tetrahedron: Asymmetry  2007,  18:  2305 
  CrossrefSearch in Google Scholar
• 11a Tang W.-J. Tan J. Xu L.-J. Lam K.-H. Fan Q.-H. Chan ASC. Adv. Synth. Catal.  2010,  352:  1055 
  Search in Google Scholar
• 11b Tang W.-J. Sun Y.-W. Xu L.-J. Wang T.-L. Fan Q.-H. Lam K.-H. Chan ASC. Org. Biomol. Chem.  2010,  8:  3464 
  Search in Google Scholar
• 12a Mamat C. Flemming A. Köckerling M. Steinbach J. Wuest FR. Synthesis  2009,  3311 
• 12b Ishikawa S. Manabe K. Tetrahedron  2010,  66:  297 
  Search in Google Scholar
• 13 Michel B, Blandine L, and Sonia R. inventors; PCT Int. Appl. WO  2002012253. 

References

• 1a Keay JG. In Comprehensive Organic Synthesis   Vol. 8:  Pergamon; Oxford: 1991.  p.579 
  Search in Google Scholar
• 1b Katrizky AR. Rachwal S. Bachwal B. Tetrahedron  1996,  52:  15031 
  Search in Google Scholar
• 1c Barton DH. Nakanishi K. Meth-Cohn O. In Comprehensive Natural Products Chemistry   Vol. 1-9:  Elsevier; Oxford: 1999. 
  Search in Google Scholar
• 2 Wang W.-B. Lu S.-M. Yang P.-Y. Han X.-W. Zhou Y.-G. J. Am. Chem. Soc.  2003,  125:  10536 
  CrossrefSearch in Google Scholar
• For recent reviews on hydrogenation of heteroaromatic compounds, see:
• 3a Dyson PJ. Dalton Trans.  2003,  2964 
• 3b Glorius F. Org. Biomol. Chem.  2005,  3:  4171 
  Search in Google Scholar
• 3c Lu S.-M. Han X.-W. Zhou Y.-G. Chin. J. Org. Chem.  2005,  25:  634 
  Search in Google Scholar
• 3d Zhou Y.-G. Acc. Chem. Res.  2007,  40:  1357 
  Search in Google Scholar
• 3e Kuwano R. Heterocycles  2008,  76:  909 
  Search in Google Scholar
• For our group’s work on the asymmetric hydrogenation of quinolines, see:
• 4a Lu S.-M. Han X.-W. Zhou Y.-G. Adv. Synth. Catal.  2004,  346:  909 
  Search in Google Scholar
• 4b Yang P.-Y. Zhou Y.-G. Tetrahedron: Asymmetry  2004,  15:  1145 
  Search in Google Scholar
• 4c Zhao Y.-J. Wang Y.-Q. Zhou Y.-G. Chin. J. Catal.  2005,  26:  737 
  Search in Google Scholar
• 4d Lu S.-M. Wang Y.-Q. Han X.-W. Zhou Y.-G. Angew. Chem. Int. Ed.  2006,  45:  2260 
  Search in Google Scholar
• 4e Wang D.-W. Zeng W. Zhou Y.-G. Tetrahedron: Asymmetry  2007,  18:  1103 
  Search in Google Scholar
• 4f Wang X.-B. Zhou Y.-G. J. Org. Chem.  2008,  73:  5640 
  Search in Google Scholar
• 4g Wang D.-W. Wang X.-B. Wang D.-S. Lu S.-M. Zhou Y.-G. Li Y.-X. J. Org. Chem.  2009,  74:  2780 
  Search in Google Scholar
• 4h Wang D.-W. Wang D.-S. Chen Q.-A. Zhou Y.-G. Chem. Eur. J.  2010,  16:  1133 
  Search in Google Scholar
• 4i Wang D.-S. Zhou Y.-G. Tetrahedron Lett.  2010,  51:  3014 
  Search in Google Scholar
• For other groups’ work on metal-catalyzed asymmetric hydrogenation of quinolines, see:
• 5a Fache F. Synlett  2004,  2827 
• 5b Fujita K.-I. Kitatsuji C. Furukawa S. Yamaguchi R. Tetrahedron Lett.  2004,  45:  3215 
  Search in Google Scholar
• 5c Xu L.-J. Lam K.-H. Ji J.-X. Wu J. Fan Q.-H. Lo W.-H. Chan ASC. Chem. Commun.  2005,  1390 
• 5d Lam K.-H. Xu L.-J. Feng L.-C. Fan Q.-H. Lam F.-L. Lo W.-H. Chan ASC. Adv. Synth. Catal.  2005,  347:  1755 
  Search in Google Scholar
• 5e Wu J. Chan ASC. Acc. Chem. Res.  2006,  39:  711 
  Search in Google Scholar
• 5f Reetz MT. Li X.-G. Chem. Commun.  2006,  2159 
• 5g Qiu L. Kwong FY. Wu J. Lam WH. Chan S. Yu W.-Y. Li Y.-M. Guo R. Zhou Z. Chan ASC. J. Am. Chem. Soc.  2006,  128:  5955 
  Search in Google Scholar
• 5h Yamagata T. Tadaoka H. Nagata M. Hirao T. Kataoka Y. Ratovelomanana-Vidal V. Genet JP. Mashima K. Organometallics  2006,  25:  2505 
  Search in Google Scholar
• 5i Chan S.-H. Lam K.-H. Li Y.-M. Xu L.-J. Tang W.-J. Lam F.-L. Lo W.-H. Yu W.-Y. Fan Q.-H. Chan ASC. Tetrahedron: Asymmetry  2007,  18:  2625 
  Search in Google Scholar
• 5j Deport C. Buchotte M. Abecassis K. Tadaoka H. Ayad T. Ohshima T. Genet J.-P. Mashima K. Ratovelomanana-Vidal V. Synlett  2007,  2743 
• 5k Li Z.-W. Wang T.-L. He Y.-M. Wang Z.-J. Fan Q.-H. Pan J. Xu L.-J. Org. Lett.  2008,  10:  5265 
  Search in Google Scholar
• 5l Zhou H.-F. Li Z.-W. Wang Z.-J. Wang T.-L. Xu L.-J. He Y.-M. Fan Q.-H. Pan J. Gu L.-Q. Chan ASC. Angew. Chem. Int. Ed.  2008,  47:  8464 
  Search in Google Scholar
• 5m Lu S.-M. Bolm C. Adv. Synth. Catal.  2008,  350:  1101 
  Search in Google Scholar
• 5n Mršić N. Lefort L. Boogers JAF. Minnaard AJ. Feringa BL. de Vries JG. Adv. Synth. Catal.  2008,  350:  1081 
  Search in Google Scholar
• 5o Eggenstein M. Thomas A. Theuerkauf J. Franciò G. Leitner W. Adv. Synth. Catal.  2009,  351:  725 
  Search in Google Scholar
• 5p Wang C. Li C.-Q. Wu X.-F. Pettman A. Xiao J.-L. Angew. Chem. Int. Ed.  2009,  48:  6524 
  Search in Google Scholar
• 5q Tadaoka H. Cartigny D. Nagano T. Gosavi T. Ayad T. Genet J.-P. Ohshima T. Ratovelomanana-Vidal V. Mashima K. Chem. Eur. J.  2009,  15:  9990 
  Search in Google Scholar
• 5r Wang Z.-J. Zhou H.-F. Wang T.-L. He Y.-M. Fan Q.-H. Green Chem.  2009,  11:  767 
  Search in Google Scholar
• 5s Parekh V. Ramsden JA. Wills M. Tetrahedron: Asymmetry  2010,  21:  1549 
  Search in Google Scholar
• 5t Gou F.-R. Li W. Zhang XM. Liang Y.-M. Adv. Synth. Catal.  2010,  352:  2441 
  Search in Google Scholar
• For the work on organocatalytic asymmetric hydrogenation of quinolines, see:
• 6a Rueping M. Antonchick AP. Theissmann T. Angew. Chem. Int. Ed.  2006,  45:  3683 
  Search in Google Scholar
• 6b Rueping M. Theissmann T. Raja S. Bats JWP. Adv. Synth. Catal.  2008,  350:  1001 
  Search in Google Scholar
• 6c Guo Q.-S. Du D.-M. Xu J. Angew. Chem. Int. Ed.  2008,  47:  759 
  Search in Google Scholar
• For selected examples on asymmetric hydrogenation of other heteroaromatic compounds, see, for quinoxalines:
• 7a Cobley CJ. Henschke JP. Adv. Synth. Catal.  2003,  345:  195 
  Search in Google Scholar
• 7b Mršić N. Jerphagnon T. Minnaard AJ. Feringa BL. de Vries JG. Adv. Synth. Catal.  2009,  351:  2549 
  Search in Google Scholar
• 7c Tang W.-J. Xu L.-J. Fan Q.-H. Wang J. Fan B.-M. Zhou Z.-Y. Lam K.-H. Chan ASC. Angew. Chem. Int. Ed.  2009,  48:  9135 
  Search in Google Scholar
• 7d Cartigny D. Nagano T. Ayad T. Genet JP. Ohshima T. Mashima K. Ratovelomanana-Vidal V. Adv. Synth. Catal.  2010,  352:  1886 
  Search in Google Scholar
• For furans, see:
• 7e Ohta T. Miyake T. Seido N. Kumobayashi H. Takaya H. J. Org. Chem.  1995,  60:  357 
  Search in Google Scholar
• 7f Kaiser S. Smidt SP. Pfaltz A. Angew. Chem. Int. Ed.  2006,  45:  5194 
  Search in Google Scholar
• 7g Feiertag P. Albert M. Nettekoven U. Spindler F. Org. Lett.  2006,  8:  4133 
  Search in Google Scholar
• For pyridines, see:
• 7h Raynor SA. Thomas JM. Raja R. Johnson BFG. Belle RG. Mantle MD. Chem. Commun.  2000,  1925 
• 7i Glorius F. Spielkamp N. Holle S. Goddard R. Lehmann CW. Angew. Chem. Int. Ed.  2004,  43:  2850 
  Search in Google Scholar
• 7j Legault CY. Charette AB. J. Am. Chem. Soc.  2005,  127:  8966 
  Search in Google Scholar
• 7k Wang X.-B. Zeng W. Zhou Y.-G. Tetrahedron Lett.  2008,  49:  4922 
  Search in Google Scholar
• For indoles, see:
• 7l Kuwano R. Sato K. Kurokawa T. Karube D. Ito Y. J. Am. Chem. Soc.  2000,  122:  7614 
  Search in Google Scholar
• 7m Kuwano R. Kaneda K. Ito T. Sato K. Kurokawa T. Ito Y. Org. Lett.  2004,  6:  2213 
  Search in Google Scholar
• 7n Kuwano R. Kashiwabara M. Org. Lett.  2006,  8:  2653 
  Search in Google Scholar
• 7o Baeza A. Pfaltz A. Chem. Eur. J.  2010,  16:  2036 
  Search in Google Scholar
• 7p Wang D.-S. Chen Q.-A. Li W. Yu C.-B. Zhou Y.-G. Zhang XM. J. Am. Chem. Soc.  2010,  132:  8909 
  Search in Google Scholar
• For pyrroles, see:
• 7q Kuwano R. Kashiwabara M. Ohsumi M. Kusano H. J. Am. Chem. Soc.  2008,  130:  808 
  Search in Google Scholar
• 8 Wang Z.-J. Deng G.-J. Li Y. He Y.-M. Tang W.-J. Fan Q.-H. Org. Lett.  2007,  9:  1243 
  CrossrefSearch in Google Scholar
• 9 Wang D.-S. Zhou J. Wang D.-W. Guo Y.-L. Zhou Y.-G. Tetrahedron Lett.  2010,  51:  525 
  CrossrefSearch in Google Scholar
• 10 Jahjah M. Alame M. Pellet-Rostaing S. Lemaire M. Tetrahedron: Asymmetry  2007,  18:  2305 
  CrossrefSearch in Google Scholar
• 11a Tang W.-J. Tan J. Xu L.-J. Lam K.-H. Fan Q.-H. Chan ASC. Adv. Synth. Catal.  2010,  352:  1055 
  Search in Google Scholar
• 11b Tang W.-J. Sun Y.-W. Xu L.-J. Wang T.-L. Fan Q.-H. Lam K.-H. Chan ASC. Org. Biomol. Chem.  2010,  8:  3464 
  Search in Google Scholar
• 12a Mamat C. Flemming A. Köckerling M. Steinbach J. Wuest FR. Synthesis  2009,  3311 
• 12b Ishikawa S. Manabe K. Tetrahedron  2010,  66:  297 
  Search in Google Scholar
• 13 Michel B, Blandine L, and Sonia R. inventors; PCT Int. Appl. WO  2002012253. 

• Supplementary Material