Iridium Complex-Catalyzed Transfer Hydrogenation of N-Heteroarenes and Tentative Asymmetric Synthesis.

An iridium-catalyzed transfer hydrogenation of N-heteroarenes to access a series of substituted 1,2,3,4-tetrahydroquinoline derivatives in excellent yields is disclosed. This transformation is distinguished with water-soluble and air-stable iridium complexes as the catalyst, formic acid as the hydrogen source, mild reaction conditions, and broad functional group compatibility. Most importantly, a tentative chiral N,N-chelated Cp*Ir(III) complex-catalyzed enantioselective transfer hydrogenation is also presented, affording chiral products in excellent yields and good enantioselectivities.

Introduction

Reduction of N-heteroarenes to their partially or completely saturated congeners not only represents a promising method for organic synthesis for producing fine and bulk chemicals but also is a fundamentally important reaction in the petrochemical industry.[1] Particularly, the reductive products 1,2,3,4-tetrahydroquinoline derivatives constitute ubiquitous motifs in an abundance of natural products, bioactive molecules, pharmaceuticals, and agrochemicals,[2] for example, the natural product (−)-galipinine[3] and (−)-cuspareine[4] and the drug and biomolecules oxamniquine,[5] paroxetine,[2b] and argatroban[6] (Scheme ).

Scheme 1

Representative Natural Products and Biomolecules that Contain Saturated N-Heteroarene Units

Over the past few decades, great efforts have been devoted to develop an efficient method for synthesis of these useful 1,2,3,4-tetrahydroquinoline derivatives. Among the reported methods, the reduction of parent arenes, including catalytic hydrogenation[7] and transfer hydrogenation,[8] is one of the best direct strategies for synthesis of tetrahydroquinolines. Obviously, metal-participated catalytic hydrogenation, which is a fundamentally important reaction employed in industry and organic synthesis, has been widely used for the synthesis of tetrahydroquinoline derivatives, along with asymmetric hydrogenation. For example, various catalytic systems based on transition metals, such as Ru,[9] Rh,[10] Ir,[11] Pd,[12] Fe,[13] and Co,[14] have been applied in the hydrogenation of N-heteroarenes, which exhibit good reactivities and selectivities. However, the turnover number, turnover frequency, and substrate expansion have been considered to be important but still challenging.[8f]

Transfer hydrogenation has also received considerable attention due to the simple operations. In contrast to traditional hydrogenation, transfer hydrogenation makes use of alcohols,[15] silane,[16] hantzsch ester,[17] and formic acid[18] as hydrogen donors, which is widely employed in the reduction of C=O, C=N, and C=C bonds. In addition, formic acid, which is safe, accessible, and highly stable, has been used extensively.

Cyclometalated iridium complexes have been the most attractive and powerful catalysts for efficient transfer hydrogenation.[19] In recent years, although tremendous achievements have been made in transfer hydrogenation of N-heteroarenes,[20] the asymmetric transfer hydrogenation of N-heteroarenes displays a more difficult task due to the requisite enantiocontrol in the concurrent construction of chiral centers.[21] Therefore, the development of a new and efficient catalytic system for highly enantioselective transfer hydrogenation of N-heteroarenes remains a highly desirable and challenging task.

With our continued interest in iridium complex-catalyzed transfer hydrogenation, we found that Ir–H complexes could be obtained by the decomposition of formic acid through iridium complexes.[22] By designing and synthesizing a series of achiral and chiral iridium complexes, we envision that the reductive Ir–H complexes could contribute to the synthesis of tetrahydroquinolines.

Herein, we describe an efficient, practical, and convenient transfer hydrogenation of N-heteroarenes using formic acid as a hydrogen source and iridium complexes as a catalyst (Scheme b), providing a variety of substituted tetrahydroquinoline derivatives in excellent yields under mild reaction conditions. Meanwhile, a tentative asymmetric transfer hydrogenation is also conducted to access chiral products in excellent yields and good enantioselectivities.

Scheme 2

Reduction of N-Heteroarene Compounds

Results and Discussion

Initial investigations began by evaluating the Ir complexes to study transfer hydrogenation of N-heteroarenes (Table ). To our delight, TC-1 gave the desired product 2aa in the yield of 65% (entry 1). Then, different-substituted Tang’s catalysts had been screened for exploring better catalytic efficiency (entries 2–6). However, slightly decreased yields were afforded by employing TC-2–TC-6[18c] in this catalytic system. Previous work also demonstrated that hydrogen sources played an important role in transfer hydrogenation. Next, we turned our attention to explore different hydrogen sources. As it is evident by the result compiled in Table , lower yields had been obtained using HCO2Na and HCO2H/NEt3 as hydrogen sources (entries 7–9). In the process of studying the reaction, we found that the substrates cannot dissolve well in the water, which may lead to low transformation in this catalytic system. Based on this, a rapid screening of organic solvents was performed. As shown in Table (entries 10–15), only MeOH gave the desired product 2aa in moderate yields by evaluating the common organic solvents. A slightly increased yield of 73% was afforded by raising the temperature to 80 °C (entry 16). To further improve the reactivity of the catalyst, further optimized conditions were explored. Combining the excellent water solubility of these iridium catalysts and the good solubility of the substrates in organic solvents, we envisioned that the mixture of MeOH and H2O as a solvent can dissolve both the substrates and iridium catalyst, which may improve this catalytic efficiency. As expected, the mixed solvent was demonstrated as optimal medium (entry 17).

Table 1

Optimization of Reaction Parameters in the Iridium Complex-Catalyzed Transfer Hydrogenation of N-Heteroarenesa

entry	catalyst	hydrogen donor	solvent	yield/%b
1	TC-1	HCO2H	H2O	65
2	TC-2	HCO2H	H2O	60
3	TC-3	HCO2H	H2O	54
4	TC-4	HCO2H	H2O	58
5	TC-5	HCO2H	H2O	52
6	TC-6	HCO2H	H2O	53
7	TC-1	HCO2Na	H2O	39
8c	TC-1	HCO2H/Et3N	H2O	44
9d	TC-1	HCO2H/HCOONa	H2O	45
10	TC-1	HCO2H	DMSO	<5
11	TC-1	HCO2H	toluene	24
12	TC-1	HCO2H	THF	<5
13	TC-1	HCO2H	CH2Cl2	17
14	TC-1	HCO2H	MeCN	21
15	TC-1	HCO2H	MeOH	53
16e	TC-1	HCO2H	H2O	73
17f	TC-1	HCO2H	H2O/MeOH	95(92)

Reaction conditions: 1a (0.25 mmol), solvent (2.0 mL), catalyst (1.0 mol %), and hydrogen donor (5.0 equiv) at room temperature under air for 12 h.

Determined by GC–MS using dodecane as the internal standard. The number in the parentheses is the isolated yield.

The reaction was carried out with 5.0 equiv of HCO2H and 2.0 equiv of Et3N.

The reaction was carried out with 5.0 equiv of HCOOH and 2.0 equiv of HCOONa.

The reaction was carried out at 80 °C.

H2O/MeOH = 1:1.

With the optimal catalytic system in hand, the substrate scope of transfer hydrogenation of N-heteroarenes was examined, the results of which are summarized in Scheme . Generally, various 2-aryl quinoline derivatives, including electron-donating or electron-withdrawing substituents on the phenyl group, were employed in this catalytic hydrogenation transfer reduction, affording the desired products in good to excellent yields (Table ). For example, electron-donating substituents of methyl, methoxy, and hydroxy on the phenyl ring were well compatible in this system, delivering the corresponding products in the yields of 84–93% (2ab–2af). This catalytic system also demonstrated high activities in the halogen-substituted 2-aryl quinolines (1ag–1ak and 1an), which can achieve various N-heteroarenes through functional group transformation. In addition, strong electron-drawing substituents, such as −NO2 and −CF3, on the phenyl ring were selectively reduced to the corresponding products in the yield of 86 and 88%, respectively (2al and 2am). Notably, substrates with heterocyclic rings, such as 2-furyl and 2-thiophenyl, on quinoline conducted smoothly, delivering desired products 2ao and 2ap in high yields. Besides, different substituents on the ring of quinolines were next examined. Notably, both methoxy and chlorine groups were well tolerated (2aq–2as). At the same time, alkyl-substituted quinoline on the 2-position also worked well, leading to the reduction product 2at in 90% yield. Gratifyingly, 3-position-substituted quinoline substrates had been proven to be suitable candidates for this transformation. For instance, 1au–1ax were selectively converted to 1,2,3,4-tetrahydroquinoline products 2au–2ax in the yields of 92–95%.

Scheme 3

Gram-Scale Transformation

Table 2

Scope of Monosubstituted N-Heteroarenes for Transfer Hydrogenationa

Standard conditions: a solution of 1 (0.25 mmol), TC-1 (1.0 mol %), and HCOOH (5.0 equiv) in H2O (2.0 mL) and MeOH (2.0 mL) at room temperature under air for 12 h. Yield of the isolated product.

Encouraged by results with monosubstituted quinolines, we wonder whether this catalytic system could be extended to disubstituted N-heteroarenes (Table ). Obviously, 2-aryl/alkyl and 3-aryl quinoline substrates featuring fluorine, methyl, and methoxy groups were successfully converted to the corresponding 1,2,3,4-tetrahydroquinoline congener in excellent yields (90–94%) (2ba–2bd). Except for quinolines, benzannulated quinolines, such as 1be–1bg, could also be applied in this catalytic transfer hydrogenation system, affording the corresponding hydrogenated products 2be–2bg in excellent yields.

Table 3

Substrate Scope of Disubstituted N-Heteroarenes for the Transfer Hydrogenationa

Standard conditions: a solution of 1 (0.25 mmol), TC-1 (1.0 mol %), and HCOOH (5.0 equiv) in H2O (2.0 mL) and MeOH (2.0 mL) at room temperature under air for 12 h. Yield of the isolated product.

The relative stereochemistry of the major diastereomer was determined by NMR.

Chiral tetrahydroquinolines are prevalent scaffolds in bioactive natural products and pharmaceuticals.[2] Encouraged by those promising results, we are interested in realizing the asymmetric hydrogen transformation. With abovementioned optimal reaction conditions in hand, we envisage whether chiral iridium complexes can be used as catalysts for the asymmetric catalytic conversion of this reaction. Based on this, we designed and synthesized a series of chiral iridium complexes Ir-1–Ir-5. The absolute configuration of the chiral iridium complexes Ir-1 is unambiguously confirmed by X-ray structure analysis (Figure ).

Figure 1

Single-crystal X-ray diffraction of chiral Ir-1 (CCDC Numbers: 2046295).

With these chiral catalysts Ir-1–Ir-5 in hand, optimization of chiral Ir catalysts was performed. Simple catalyst screening showed that the chiral catalyst Ir-1 was the optimal catalyst, which demonstrated that the introduction of the substituents into the pyridyl scaffold is unfavorable to improve the enantioselectivity (Table , entries 1–5). Next, an attempt of solvent screening did not have improvement on reactivities and enantioselectivities (Table , entries 6–9). It should be noted that when the reaction temperature was increased, the yield could be improved, but the enantioselectivity remained almost unchanged (Table , entries 10 and 11). To obtain better enantioselectivity, different hydrogen donors were also tested (Table , entries 12–14), which found that HCO2H was still the best hydrogen donor. Increasing HCO2H loading to the amount of 10.0 equiv did not improve enantioselectivity but significantly enhanced reactivity (Table , entry 12). Finally, evaluation of various parameters established methanol and water as optimal solvents, HCO2H as the optimal hydrogen ,donor and chiral Ir-1 as the best catalyst (Table , entry 15).

Table 4

Optimization of the Asymmetric Transfer Hydrogenation of 2-Arylquinolinea

entry	catalyst	hydrogen donor	solvent	yield/%b	ee/%c
1	Ir-1	HCOOH	H2O	71	65
2	Ir-2	HCOOH	H2O	65	32
3	Ir-3	HCOOH	H2O	63	54
4	Ir-4	HCOOH	H2O	60	57
5	Ir-5	HCOOH	H2O	54	10
6	Ir-1	HCOOH	CH3OH	68	45
7	Ir-1	HCOOH	CH2Cl2	70	62
8	Ir-1	HCOOH	toluene	54	60
9	Ir-1	HCOOH	MeCN	45	59
10d	Ir-1	HCOOH	H2O	76	59
11e	Ir-1	HCOOH	H2O	80	61
12f	Ir-1	HCOOH	H2O	90	65
13	Ir-1	HCOONa	H2O	<5
14g	Ir-1	HCOOH/HCOONa	H2O	21	61
15f,h	Ir-1	HCOOH	H2O/MeOH	95	66

Reaction conditions: 1a (0.25 mmol), solvent (2.0 mL), catalyst (1.0 mol %), and hydrogen donor (5.0 equiv) at room temperature under air for 12 h.

Determined by GC–MS using dodecane as the internal standard. The number in the parentheses is the isolated yield.

ee values were determined by HPLC with an OD-H column.

The reaction was carried out at 40 °C.

The reaction was carried out at 60 °C.

The reaction was carried out with 10.0 equiv of HCOOH.

The reaction was carried out with 5.0 equiv of HCOOH and 2.0 equiv of HCO2Na.

H2O/MeOH = 1.0/1.0 mL.

With optimal conditions in hand, the scope of the asymmetric transfer hydrogenation was examined, the results of which are summarized in Table . As can be seen in Table , all the 2-aryl-substituted substrates could be almost completely transferred into desired products with good enantioselectivities, regardless of the electronic properties of the C2 substituents, such as methyl, n-butyl, and chlorine (2ab, 2ad, 2ai, and 2aj). In addition, the thienyl on the 2-position of quinoline was compatible with this catalytic system, giving 2ao in the yield of 90 and 63% ee. However, the position of the substituent on quinoline is critical for enantioselectivity. For instance, all 3-substituted substrates afforded low enantioselectivities (1ba and 1av). It should be pointed out that 1H NMR analysis of Ir-1 in CDCl3 revealed that the diastereoselectivity of the chiral iridium center is 67:33, which definitely affected the enantioselectivity of this transfer hydrogenation reaction. Moreover, recrystallization and other strategies did not improve diastereoselectivity. More discussions and design of new chiral iridium catalysts are underway.

Table 5

Scope of the Asymmetric Transfer Hydrogenation of Substituted Quinolinea

Standard conditions: a solution of 1 (0.25 mmol), Ir-1 (1.0 mol %), and HCOOH (5.0 equiv) in H2O (2.0 mL) and MeOH (2.0 mL) at room temperature under air for 12 h. Yield of the isolated product.

To explore the potential application, a gram-scale transformation to synthesize optical 2-(4-chlorophenyl)-1,2,3,4-tetrahydroquinoline (2aj) was performed under standard conditions (Scheme ). Interestingly, the optical purity of product 2aj can be increased to 99% ee by a simple recrystallization operation with CH2Cl2.

Based on the experimental results and previous study, we proposed a mechanism of 1,4-hydride addition (Scheme ).[8c,11b,23] Initially, protonation of quinolines by HCOOH was proceeded to give Int-I. Then, the Ir–H complexes, which were achieved by iridium-catalyzed decarbondioxidation of formic acid in rapid sequence, were delivered to the Int-II via a 1,4-addition fashion. Finally, protonation and 1,2-addition of isomerization quinoline gave the desired product. Notably, this mechanism explained why the asymmetric transfer hydrogenation occurred in 2-substituted quinoline to realize better enantioselectivities, compared to 3-substituted quinoline.

Scheme 4

Possible Reaction Pathways for the TH of Quinolines

Conclusions

In conclusion, we have developed an iridium complex-catalyzed transfer hydrogenation of substituted quinolines, and a variety of highly functionalized and useful tetrahydroquinoline derivatives were afforded in excellent yields. The advantages of using an environmentally benign solvent and renewable hydride donor and purification provide great potential of practical synthesis. Moreover, this reaction can be applied to large-scale and asymmetric synthesis using chiral iridium complexes. Ongoing investigations on exploration of asymmetric transfer hydrogenation and application in the synthesis of optically active drugs with tetrahydroquinoline skeletons are in progress.

Experimental Section

General Information

1H and 13C NMR spectra were recorded using a 400 MHz NMR spectrometer. Chemical shifts were reported in ppm from the solvent resonance as the internal reference (CDCl3 δH = 7.26 ppm, downfield from TMS, δC = 77.16 ppm). Gas chromatography–mass spectrometry (GC–MS) was detected using electron ionization. TLC was performed using commercially prepared 100–400 mesh silica gel plates and visualization was affected at 254 nm. High-performance liquid chromatography (HPLC) analyses were performed with an Agilent 1100 instrument using Chiralcel OD-H and Chiralpak AD-H or AS-H columns (0.46 cm diameter × 25 cm length). Optical rotations and MS spectra were recorded on a PerkinElmer polarimeter (model 341) and an ESI-ion trap mass spectrometer (Shimadzu LCMS-IT-TOF), respectively. Starting materials of all the organosilanes and alcohols were commercially available.

General Procedure for the Synthesis of Substituted Quinoline Derivatives

To a stirred solution of 2-aminobenzaldehyde (1.21 g, 0.01 mol) and ketone (0.012 mol) in EtOH (20 mL) at room temperature was added KOH (2 g, 0.03 mol). The resulting mixture was then heated at reflux temperature overnight. After the mixture had cooled down to room temperature, the solvent was removed in vacuo. Then, ethyl acetate (20 mL) was added. The mixture was filtered, and the residue was washed with ethyl acetate (3 × 5 mL). The combined organic mixture was concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate/petroleum = 1/20) to give a white solid.

General Procedure for Transfer Hydrogenation of N-Heterocycles

To a 25.0 mL Schlenk tube was added the mixture of the quinolines (0.25 mmol), TC-1 catalyst (1.0 mol %, 1.4 mg), and HCOOH (5.0 equiv, 57 mg, 47 μL) in water (2.0 mL) successively. The mixture was stirred at room temperature for 12 h under air. After the reaction was completed, the mixture was diluted with H2O (15.0 mL), neutralized with NaHCO3, and extracted with EtOAc (10.0 mL × 3). The organic extract was washed with brine (10.0 mL × 3) and dried over anhydrous MgSO4. After removal of the EtOAc under vacuum, the crude product was purified by column chromatography on silica gel with hexanes or petroleum ether/ethyl acetate (5:1 to 50:1) to give the desired products.

General Procedure for Asymmetric Transfer Hydrogenation of N-Heterocycles

To a 25.0 mL Schlenk tube was added the mixture of the quinolines (0.25 mmol), chiral Ir-1 catalyst (1.0 mol %, 1.7 mg), and HCOOH (10.0 equiv, 95 μL) in water (1.0 mL)/MeOH (1.0 mL) successively. The mixture was stirred at room temperature for 12 h under air. After the reaction was completed, the mixture was diluted with H2O (15.0 mL), neutralized with NaHCO3, and extracted with EtOAc (10.0 mL × 3). The organic extract was washed with brine (10.0 mL × 3) and dried over anhydrous MgSO4. After removal of the EtOAc under vacuum, the crude product was purified by column chromatography on silica gel with hexanes or petroleum ether/ethyl acetate (5:1 to 50:1) to give the desired products. The enantioselectivities were determined using an OD-H column.

General Procedure for the Synthesis of Chiral Ir-Catalysts

To a solution of ligand (4.5 mmol) in 50.0 mL of CH2Cl2 was added the powder of [Cp*IrCl2]2 (2.0 mmol). The resultant orange solution was stirred overnight. CH2Cl2 was removed under reduced pressure, and the resultant yellow solid was dissolved in a minimum amount of CH2Cl2. Then, a large amount of EtOAc slowly was added to precipitate an orange solid as the desired product, which was isolated by reduced-pressure filtration and further dried under vacuum at room temperature.

(R)-2-Phenyl-1,2,3,4-tetrahydroquinoline (2aa)

[α]D20 = +29.6 (c 0.43, CH2Cl2).[24a] Yield: 94% (49.6 mg) as a light-yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.48 (ddd, J = 7.4, 5.2, 1.0 Hz, 4H), 7.43–7.36 (m, 1H), 7.17–7.07 (m, 2H), 6.78 (t, J = 6.9 Hz, 1H), 6.64 (d, J = 7.8 Hz, 1H), 4.57–4.47 (m, 1H), 4.10 (s, 1H), 3.04 (ddd, J = 15.9, 10.4, 5.2 Hz, 1H), 2.85 (dt, J = 10.2, 4.6 Hz, 1H), 2.28–2.18 (m, 1H), 2.17–2.06 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 144.7, 144.6, 129.2, 128.5, 127.3, 126.8, 126.5, 120.8, 117.1, 113.9, 56.1, 30.9, 26.3. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 9.161 min, tmajor = 11.721 min, and 63% ee.

2-(p-tolyl)-1,2,3,4-tetrahydroquinoline (2ab)

[α]D20 = +2.7 (c 0.34, CH2Cl2).[17a] Yield: 90% (50.2 mg) as a light-yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.33 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 7.3 Hz, 2H), 6.70 (s, 1H), 6.57 (d, J = 7.9 Hz, 1H), 4.44 (dd, J = 9.4, 3.2 Hz, 1H), 4.32–3.75 (m, 1H), 2.95 (dd, J = 10.8, 5.5 Hz, 1H), 2.80 (dd, J = 12.8, 8.2 Hz, 1H), 2.41 (s, 3H), 2.19–2.11 (m, 1H), 2.09–1.97 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 144.9, 141.9, 137.1, 129.3, 129.3, 126.9, 126.5, 120.9, 117.2, 114.0, 56.1, 31.1, 26.6, 21.2. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 7.175 min, tmajor = 12.050 min, and 71% ee.

2-(m-Tolyl)-1,2,3,4-tetrahydroquinoline (2ac)

Yield: 92% (52.3 mg) as a light-yellow oil;[24c]1H NMR (400 MHz, CDCl3): δ 7.31 (dd, J = 14.1, 6.3 Hz, 1H), 7.05 (dd, J = 16.5, 8.7 Hz, 4H), 6.88 (dd, J = 8.1, 2.4 Hz, 1H), 6.70 (t, J = 7.3 Hz, 1H), 6.59 (d, J = 7.9 Hz, 1H), 4.46 (dd, J = 9.4, 3.2 Hz, 1H), 4.36–3.90 (m, 1H), 3.85 (s, 3H), 2.97 (ddd, J = 16.3, 10.7, 5.5 Hz, 1H), 2.79 (dt, J = 16.3, 4.7 Hz, 1H), 2.16 (td, J = 8.4, 4.2 Hz, 1H), 2.10–1.96 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 159.9, 146.6, 144.7, 129.6, 129.3, 126.9, 120.9, 118.9, 117.3, 114.1, 112.8, 112.1, 56.3, 55.3, 31.0, 26.5.

2-(4-Butylphenyl)-1,2,3,4-tetrahydroquinoline (2ad)

[α]D20 = +5.0 (c 0.32, CH2Cl2).[17a] Yield: 93% (61.6 mg) as a light-yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.36 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.07 (t, J = 6.9 Hz, 2H), 6.71 (t, J = 7.3 Hz, 1H), 6.58 (d, J = 8.2 Hz, 1H), 4.46 (dd, J = 9.4, 3.2 Hz, 1H), 4.07 (s, 1H), 2.99 (ddd, J = 16.3, 10.8, 5.5 Hz, 1H), 2.81 (dt, J = 16.3, 4.6 Hz, 1H), 2.75–2.61 (m, 2H), 2.28–2.13 (m, 1H), 2.12–1.97 (m, 1H), 1.73–1.62 (m, 2H), 1.49–1.36 (m, 2H), 1.01 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 144.9, 142.2, 142.0, 129.3, 128.6, 126.9, 126.5, 120.9, 117.1, 114.0, 56.1, 35.4, 33.8, 31.1, 26.6, 22.5, 14.1. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 5.909 min, tmajor = 6.853 min, and 80% ee.

2-(3-Methoxyphenyl)-1,2,3,4-tetrahydroquinoline (2ae)

Yield: 90% (53.8 mg) as a white solid (53–57 °C);[24a]1H NMR (400 MHz, CDCl3): δ 7.32 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 16.7, 8.7 Hz, 4H), 6.95–6.82 (m, 1H), 6.70 (t, J = 7.2 Hz, 1H), 6.58 (d, J = 7.8 Hz, 1H), 4.45 (dd, J = 9.3, 3.0 Hz, 1H), 3.98 (dd, J = 24.6, 13.2 Hz, 1H), 3.84 (d, J = 10.8 Hz, 3H), 2.97 (ddd, J = 16.2, 10.7, 5.4 Hz, 1H), 2.79 (dt, J = 16.3, 4.6 Hz, 1H), 2.17 (ddd, J = 12.9, 8.6, 4.4 Hz, 1H), 2.05 (ddd, J = 9.3, 8.8, 4.3 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 159.9, 146.6, 144.7, 129.6, 129.4, 127.0, 120.9, 119.0, 117.3, 114.1, 112.9, 112.2, 56.3, 55.3, 31.1, 26.5.

2-(1,2,3,4-Tetrahydroquinolin-2-yl)phenol (2af)

Yield: 84% (47.2 mg) as a light-yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.21 (td, J = 8.2, 1.6 Hz, 1H), 7.08 (ddd, J = 7.2, 4.6, 2.9 Hz, 3H), 6.96–6.81 (m, 3H), 6.71 (d, J = 7.8 Hz, 1H), 4.40 (dd, J = 11.6, 2.7 Hz, 1H), 3.14–2.94 (m, 1H), 2.91–2.83 (m, 1H), 2.37 (ddd, J = 17.8, 12.8, 5.5 Hz, 1H), 2.14–2.05 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 156.4, 142.6, 129.8, 129.1, 128.3, 126.9, 126.7, 123.6, 120.9, 119.9, 117.4, 117.4, 57.9, 28.6, 26.7. HRMS-ESI (m/z): calcd for C15H16NO [M + H]+, 226.1232; found, 226.1232.

2-(2-Fluorophenyl)-1,2,3,4-tetrahydroquinoline (2ag)

Yield: 89% (50.5 mg) as a colorless oil;[17a]1H NMR (400 MHz, CDCl3): δ: δ 7.53 (t, J = 7.2 Hz, 1H), 7.33–7.27 (m, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.13–7.03 (m, 3H), 6.72 (t, J = 7.4 Hz, 1H), 6.62 (d, J = 7.9 Hz, 1H), 4.90 (dd, J = 8.1, 3.4 Hz, 1H), 4.42–3.69 (m, 1H), 2.99–2.89 (m, 1H), 2.74 (dt, J = 16.3, 5.5 Hz, 1H), 2.22 (ddd, J = 12.7, 9.2, 5.5 Hz, 1H), 2.11–2.02 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 160.0 (d, J = 244 Hz), 144.5, 131.7 (d, J = 13 Hz), 129.4, 128.6 (d, J = 8 Hz), 127.9 (d, J = 4 Hz), 127.0, 124.3 (d, J = 3 Hz), 120.9, 117.4, 115.3 (d, J = 22 Hz), 114.1, 48.8 (d, J = 3 Hz), 28.8, 25.7.

2-(4-Fluorophenyl)-1,2,3,4-tetrahydroquinoline (2ah)

Yield: 90% (51.0 mg) as a colorless oil;[11d]1H NMR (400 MHz, CDCl3): δ 7.38 (dd, J = 8.3, 5.6 Hz, 2H), 7.05 (dd, J = 14.8, 8.0 Hz, 4H), 6.69 (t, J = 7.4 Hz, 1H), 6.57 (d, J = 7.8 Hz, 1H), 4.44 (dd, J = 9.3, 3.1 Hz, 1H), 4.13 (dd, J = 111.1, 23.8 Hz, 1H), 2.95 (ddd, J = 16.2, 10.6, 5.5 Hz, 1H), 2.75 (dt, J = 16.4, 4.7 Hz, 1H), 2.12 (ddd, J = 13.0, 8.4, 4.7 Hz, 1H), 2.06–1.91 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 162.1 (d, J = 243 Hz), 144.6, 140.5 (d, J = 3 Hz), 129.4, 128.1 (d, J = 8 Hz), 127.0, 120.9, 117.4, 115.3 (d, J = 21 Hz), 114.1, 55.6, 31.2, 26.3.

2-(3-Chlorophenyl)-1,2,3,4-tetrahydroquinoline (2ai)

[α]D20 = +13.8 (c 0.083, CH2Cl2).[9a] Yield: 88% (53.5 mg) as a light-yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.44 (s, 1H), 7.31 (s, 3H), 7.06 (dd, J = 12.5, 7.4 Hz, 2H), 6.71 (t, J = 7.4 Hz, 1H), 6.59 (d, J = 7.9 Hz, 1H), 4.46 (dd, J = 9.1, 3.3 Hz, 1H), 4.40–3.41 (m, 1H), 2.95 (ddd, J = 16.0, 10.4, 5.4 Hz, 1H), 2.76 (dt, J = 16.4, 4.9 Hz, 1H), 2.15 (ddd, J = 13.3, 8.5, 5.0 Hz, 1H), 2.01 (ddd, J = 13.2, 9.1, 5.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 147.0, 144.3, 134.5, 129.9, 129.3, 127.6, 127.0, 126.8, 124.8, 120.8, 117.5, 114.1, 55.8, 31.0, 26.1. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 10.145 min, tmajor = 13.810 min, and 75% ee.

2-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinoline (2aj)

[α]D20 = +28.0 (c 0.17, CH2Cl2).[17a] Yield: 93% (56.5 mg) as a yellow solid (mp: 87–90 °C); 1H NMR (400 MHz, CDCl3): δ 7.34 (s, 4H), 7.09–6.99 (m, 2H), 6.70 (d, J = 7.3 Hz, 1H), 6.57 (d, J = 7.9 Hz, 1H), 4.44 (dd, J = 9.1, 3.3 Hz, 1H), 4.29–3.61 (m, 1H), 2.91 (dd, J = 10.5, 5.5 Hz, 1H), 2.75 (dd, J = 13.1, 8.2 Hz, 1H), 2.16–2.07 (m, 1H), 1.99 (d, J = 4.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 144.4, 143.4, 133.0, 129.4, 128.7, 128.0, 127.0, 120.9, 117.5, 114.1, 55.6, 31.0, 26.2. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 10.435 min, tmajor = 18.268 min, and 81% ee.

2-(4-Bromophenyl)-1,2,3,4-tetrahydroquinoline (2ak)

Yield: 91% (65.3 mg) as a yellow solid (mp: 83–87 °C);[24a]1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.12–6.97 (m, 2H), 6.70 (s, 1H), 6.59 (d, J = 7.9 Hz, 1H), 4.45 (dd, J = 9.1, 3.3 Hz, 1H), 4.38–3.67 (m, 1H), 2.94 (ddd, J = 16.0, 10.4, 5.4 Hz, 1H), 2.75 (dt, J = 16.4, 4.9 Hz, 1H), 2.18–2.08 (m, 1H), 2.04–1.93 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 144.4, 143.9, 131.7, 129.4, 128.3, 127.0, 121.1, 120.8, 117.5, 114.1, 55.7, 31.0, 26.1.

2-(4-Nitrophenyl)-1,2,3,4-tetrahydroquinoline (2al)

Yield: 86% (54.6 mg) as a colorless oil;[24d]1H NMR (400 MHz, CDCl3): δ 7.34–7.22 (m, 1H), 7.13–6.95 (m, 4H), 6.73 (s, 1H), 6.60 (d, J = 7.8 Hz, 1H), 4.80 (dd, J = 9.1, 3.2 Hz, 1H), 4.31 (ddd, J = 148.3, 75.3, 43.0 Hz, 1H), 2.97 (dd, J = 10.4, 5.6 Hz, 1H), 2.85 (dd, J = 13.2, 8.2 Hz, 1H), 2.27 (dd, J = 8.9, 4.0 Hz, 1H), 2.15 (dd, J = 9.7, 4.9 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 149.0, 144.0, 129.4, 127.0, 126.7, 124.1, 123.6, 121.0, 117.8, 114.4, 52.0, 31.9, 26.2.

2-(4-(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinol-ine (2am)

Yield: 88% (60.9 mg) as a yellow oil;[11d]1H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.02 (dd, J = 13.4, 7.2 Hz, 2H), 6.68 (t, J = 7.3 Hz, 1H), 6.57 (d, J = 7.9 Hz, 1H), 4.52 (dd, J = 8.9, 3.3 Hz, 1H), 4.16 (dd, J = 143.7, 32.5 Hz, 1H), 2.91 (ddd, J = 15.9, 10.2, 5.4 Hz, 1H), 2.71 (dt, J = 16.4, 5.0 Hz, 1H), 2.18–2.09 (m, 1H), 2.04–1.93 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 149.0, 144.3, 129.7 (q, J = 32 Hz), 129.4, 127.1, 126.9, 125.6 (q, J = 3 Hz), 124.2 (q, J = 271 Hz), 120.8, 117.6, 114.2, 55.8, 30.9, 26.0.

2-(4-Bromo-3-fluorophenyl)-1,2,3,4-tetrahydroquinoline (2an)

Yield: 90% (69.3 mg) as a yellow solid (mp: 62–65 °C); 1H NMR (400 MHz, CDCl3): δ 7.62 (dd, J = 6.6, 2.1 Hz, 1H), 7.37–7.27 (m, 1H), 7.16–6.97 (m, 3H), 6.71 (t, J = 7.4 Hz, 1H), 6.58 (d, J = 7.9 Hz, 1H), 4.42 (dd, J = 9.2, 3.2 Hz, 1H), 4.19 (ddd, J = 115.1, 48.5, 43.5 Hz, 1H), 2.93 (ddd, J = 16.1, 10.5, 5.4 Hz, 1H), 2.74 (dt, J = 16.4, 4.8 Hz, 1H), 2.12 (ddd, J = 13.2, 8.4, 5.0 Hz, 1H), 2.02–1.91 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 158.2 (d, J = 254 Hz), 144.10, 142.22 (d, J = 4 Hz), 131.5, 129.2, 127.0 (d, J = 7 Hz), 126.9, 120.7, 117.6, 116.3 (d, J = 22Hz), 114.1, 108.9 (d, J = 11 Hz), 55.1, 31.0, 26.0. HRMS-ESI (m/z): calcd for C15H14NBrF [M + H]+, 306.0294; found, 306.0294.

2-(Thiophen-2-yl)-1,2,3,4-tetrahydroquinoline (2ao)

[α]D20 = +9.3 (c 0.41, CH2Cl2).[11d] Yield: 92% (48.4 mg) as a light-yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.28 (d, J = 5.0 Hz, 1H), 7.06 (dt, J = 8.6, 5.9 Hz, 4H), 6.74 (t, J = 7.4 Hz, 1H), 6.60 (d, J = 7.8 Hz, 1H), 4.80 (dd, J = 9.1, 3.2 Hz, 1H), 4.64–3.27 (m, 1H), 3.06–2.91 (m, 1H), 2.84 (dt, J = 16.4, 4.9 Hz, 1H), 2.27 (td, J = 8.2, 4.2 Hz, 1H), 2.20–2.10 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 148.9, 144.0, 129.4, 127.0, 126.7, 124.1, 123.6, 121.0, 117.8, 114.4, 52.0, 31.9, 26.2. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 10.191 min, tmajor = 13.024 min, and 63% ee.

2-(Furan-2-yl)-1,2,3,4-tetrahydroquinoline (2ap)

Yield: 89% (44.3 mg) as a colorless oil;[9a]1H NMR (400 MHz, CDCl3): δ: δ 7.46–7.35 (m, 1H), 7.07–6.98 (m, 2H), 6.69 (t, J = 7.4 Hz, 1H), 6.58 (d, J = 7.9 Hz, 1H), 6.37 (dd, J = 2.9, 2.0 Hz, 1H), 6.24 (d, J = 3.2 Hz, 1H), 4.57 (dd, J = 8.2, 3.6 Hz, 1H), 4.45–3.23 (m, 1H), 2.90 (ddd, J = 15.3, 9.2, 5.7 Hz, 1H), 2.79 (dt, J = 16.3, 5.5 Hz, 1H), 2.27–2.14 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 157.0, 143.8, 141.7, 129.3, 126.9, 121.0, 117.6, 114.4, 110.2, 105.2, 49.7, 26.9, 25.6.

6-Chloro-2-phenyl-1,2,3,4-tetrahydroquinoline (2aq)

[α]D20 = −6.1 (c 0.06, CH2Cl2).[24e] Yield: 95% (57.7 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.44–7.28 (m, 5H), 7.11–6.88 (m, 2H), 6.47 (d, J = 8.1 Hz, 1H), 4.44 (dd, J = 9.1, 3.3 Hz, 1H), 4.36–3.20 (m, 1H), 2.89 (ddd, J = 16.0, 10.4, 5.4 Hz, 1H), 2.71 (dt, J = 16.5, 4.9 Hz, 1H), 2.17–2.08 (m, 1H), 2.03–1.92 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 144.4, 143.3, 128.9, 128.7, 127.6, 126.7, 126.5, 122.4, 121.5, 115.0, 56.1, 30.5, 26.2. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 10.147 min, tmajor = 16.881 min, and 75% ee.

7-Methoxy-1,2,3,4-tetrahydroquinoline (2ar)

Yield: 94% (38.3 mg) as a colorless oil;[24f]1H NMR (400 MHz, CDCl3): δ 6.64–6.53 (m, 2H), 6.46 (d, J = 8.5 Hz, 1H), 3.73 (s, 3H), 3.29–3.22 (m, 2H), 3.08 (s, 1H), 2.76 (t, J = 6.5 Hz, 2H), 1.93 (dt, J = 11.9, 6.1 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 151.9, 138.8, 123.0, 115.7, 114.9, 112.9, 55.8, 42.4, 27.2, 22.5.

6-Chloro-1,2,3,4-tetrahydroquinoline (2as)

Yield: 92% (38.4 mg) as a light-yellow oil;[24b]1H NMR (400 MHz, CDCl3): δ 6.93 (d, J = 8.0 Hz, 2H), 6.41 (d, J = 8.1 Hz, 1H), 3.64 (s, 1H), 3.35–3.26 (m, 2H), 2.75 (t, J = 6.4 Hz, 2H), 1.98–1.89 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 143.3, 129.0, 126.5, 122.9, 121.2, 115.1, 41.9, 26.9, 21.8.

2-(4-Chlorophenethyl)-1,2,3,4-tetrahydroquinoline (2at)

Yield: 90% (60.9 mg) as a light-yellow oil;[24g]1H NMR (400 MHz, CDCl3): δ 7.29 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.3 Hz, 2H), 7.00 (t, J = 7.6 Hz, 2H), 6.65 (t, J = 7.3 Hz, 1H), 6.50 (d, J = 7.8 Hz, 1H), 3.40–3.23 (m, 1H), 2.89–2.71 (m, 4H), 2.07–1.98 (m, 1H), 1.88–1.80 (m, 2H), 1.76–1.67 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 144.4, 140.3, 131.7, 129.7, 129.3, 128.6, 126.8, 121.3, 117.2, 114.2, 51.0, 38.2, 31.5, 27.9, 26.2.

3-(Naphthalen-2-yl)-1,2,3,4-tetrahydroquinoline(2au)

Yield: 94% (60.8 mg) as a colorless oil;24h1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.50 (ddd, J = 15.4, 13.7, 7.1 Hz, 3H), 7.36 (d, J = 7.1 Hz, 1H), 7.07 (t, J = 7.4 Hz, 2H), 6.70 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 8.1 Hz, 1H), 4.01 (td, J = 10.4, 5.0 Hz, 1H), 3.63 (d, J = 11.1 Hz, 1H), 3.50 (t, J = 10.7 Hz, 1H), 3.16 (qd, J = 16.0, 7.7 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 144.0, 139.7, 133.9, 131.6, 129.6, 129.1, 127.1, 126.2, 125.7, 125.6, 123.0, 122.8, 121.7, 117.3, 114.3, 48.2, 34.6, 33.4.

3-(p-Tolyl)-1,2,3,4-tetrahydroquinoline (2av)

Yield: 94% (52.4 mg) as a colorless oil;[24b]1H NMR (400 MHz, CDCl3): δ 7.26–7.19 (m, 4H), 7.09 (t, J = 7.6 Hz, 2H), 6.73 (t, J = 7.4 Hz, 1H), 6.62 (d, J = 8.1 Hz, 1H), 3.81 (dd, J = 104.5, 26.1 Hz, 1H), 3.54–3.46 (m, 1H), 3.38 (t, J = 10.7 Hz, 1H), 3.25–3.14 (m, 1H), 3.06 (t, J = 8.3 Hz, 2H), 2.43 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.1, 140.9, 136.3, 129.6, 129.4, 127.2, 127.0, 121.5, 117.1, 114.1, 48.5, 38.3, 34.8, 21.1.

3-(4-Methoxyphenyl)-1,2,3,4-tetrahydroquinoline (2aw)

[α]D20 = +6.5 (c 0.09, CH2Cl2).[24b] Yield: 92% (55.0 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.20 (d, J = 8.5 Hz, 2H), 7.05 (t, J = 7.6 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H), 6.69 (t, J = 7.4 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 3.84 (s, 3H), 3.49–3.42 (m, 1H), 3.32 (t, J = 10.7 Hz, 1H), 3.14 (tdd, J = 10.1, 6.2, 3.8 Hz, 1H), 3.05–2.94 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 158.4, 144.1, 136.0, 129.59, 128.16, 127.00, 121.45, 117.12, 114.08, 114.07, 55.33, 48.62, 37.83, 34.82. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 11.696 min, tmajor = 14.063 min, and 9% ee.

3-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinoline (2ax)

Yield: 95% (57.7 mg) as a white solid (mp: 104–107 °C);[24b]1H NMR (400 MHz, CDCl3): δ 7.33 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.3 Hz, 2H), 7.09–6.99 (m, 2H), 6.69 (t, J = 7.4 Hz, 1H), 6.58 (d, J = 7.9 Hz, 1H), 3.76 (dd, J = 101.8, 29.7 Hz, 1H), 3.46 (dd, J = 11.1, 3.5 Hz, 1H), 3.32 (t, J = 10.6 Hz, 1H), 3.21–3.09 (m, 1H), 3.00 (d, J = 7.9 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 143.9, 142.4, 132.4, 129.6, 128.8, 128.6, 127.1, 121.0, 117.3, 114.2, 48.2, 38.1, 34.5.

3-(4-Fluorophenyl)-2-phenyl-1,2,3,4-tetrahydroquinol-ine (2ba)

[α]D20 = −11.4 (c 0.035, CH2Cl2). Yield: 94% (71.2 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ: δ 7.13 (ddd, J = 10.6, 6.2, 2.3 Hz, 5H), 6.89–6.70 (m, 7H), 6.64 (d, J = 7.9 Hz, 1H), 4.72 (d, J = 4.0 Hz, 1H), 3.51 (td, J = 7.1, 4.2 Hz, 1H), 3.06 (d, J = 7.1 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 162.0 (d, J = 244 Hz), 144.0, 141.0, 137.4 (d, J = 3 Hz), 129.6, 129.1 (d, J = 8 Hz), 128.7, 127.9, 127.3, 126.6, 120.5, 117.5, 114.4 (d, J = 21 Hz), 113.7, 59.7, 43.4, 29.4. HRMS-ESI (m/z): calcd for C21H19NF [M + H]+, 304.1502; found, 304.1505. The enantiomeric excess was determined by HPLC using the Daicel Chiralpak OD-H column, hexane/i-PrOH 90:10, flow rate 1.0 mL/min, UV detection at 220 nm, tminor = 11.678 min, tmajor = 12.925 min, and 12% ee.

3-(4-Methoxyphenyl)-2-phenyl-1,2,3,4-tetrahydroquino-line (2bb)

Yield: 93% (73.2 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.18 (dd, J = 5.0, 1.7 Hz, 3H), 7.10 (d, J = 7.7 Hz, 2H), 6.86 (dd, J = 6.5, 2.8 Hz, 2H), 6.73 (dd, J = 12.4, 5.3 Hz, 3H), 6.65 (dd, J = 12.2, 8.3 Hz, 3H), 4.69 (d, J = 3.9 Hz, 1H), 4.57–3.96 (m, 1H), 3.76 (s, 3H), 3.52 (td, J = 7.1, 4.0 Hz, 1H), 3.08 (d, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 158.7, 144.4, 141.4, 133.9, 129.5, 128.9, 128.7, 127.8, 127.2, 126.5, 120.6, 117.2, 113.7, 113.0, 59.8, 55.2, 43.5, 29.7. HRMS-ESI (m/z): calcd for C22H22NO [M + H]+, 316.1701; found, 316.1696.

2-Phenyl-3-(p-tolyl)-1,2,3,4-tetrahydroquinoline (2bc)

Yield: 90% (67.2 mg) as a yellow solid (mp: 118–121 °C); 1H NMR (400 MHz, CDCl3): δ 7.24–7.08 (m, 5H), 6.99 (d, J = 7.9 Hz, 2H), 6.85 (d, J = 7.2 Hz, 2H), 6.76 (dd, J = 7.2, 5.4 Hz, 3H), 6.65 (d, J = 7.9 Hz, 1H), 4.74 (d, J = 4.0 Hz, 1H), 4.66–3.98 (m, 1H), 3.67–3.44 (m, 1H), 3.22–2.92 (m, 2H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.4, 141.9, 138.2, 136.0, 129.6, 128.6, 128.5, 127.7, 127.6, 127.2, 127.1, 120.7, 117.3, 113.7, 60.4, 43.0, 29.8, 21.1. HRMS-ESI (m/z): calcd for C22H22N [M + H]+, 300.1752; found, 300.1753.

2-Benzyl-3-methyl-1,2,3,4-tetrahydroquinoline (2bd)

Yield: 92% (54.5 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.34 (t, J = 7.4 Hz, 2H), 7.30–7.25 (m, 1H), 7.21 (d, J = 7.1 Hz, 2H), 7.04 (t, J = 7.6 Hz, 1H), 6.96 (d, J = 7.4 Hz, 1H), 6.67 (t, J = 7.2 Hz, 1H), 6.54 (d, J = 7.9 Hz, 1H), 3.57 (qd, J = 6.5, 3.1 Hz, 1H), 2.82–2.72 (m, 2H), 2.55 (ddd, J = 19.8, 15.0, 8.5 Hz, 2H), 2.34–2.22 (m, 1H), 1.26 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 143.9, 140.9, 129.9, 129.2, 128.4, 126.8, 125.9, 119.9, 117.1, 114.1, 49.3, 38.1, 35.7, 30.1, 17.6. HRMS-ESI (m/z): calcd for C17H20N [M + H]+, 238.1596; found, 316.1594.

6a,7,12,12a-Tetrahydro-6H-chromeno[4,3-b]quinoline (2be)

Yield: 89% (52.8 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.26 (dd, J = 13.9, 6.6 Hz, 2H), 7.02 (t, J = 7.3 Hz, 2H), 6.97–6.86 (m, 2H), 6.66 (t, J = 7.4 Hz, 1H), 6.50 (d, J = 8.1 Hz, 1H), 4.43 (d, J = 3.4 Hz, 1H), 4.16 (dd, J = 12.7, 8.3 Hz, 2H), 3.19 (dd, J = 17.0, 6.4 Hz, 1H), 2.69 (dd, J = 17.0, 3.1 Hz, 1H), 2.54 (ddd, J = 10.2, 6.6, 3.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 153.9, 141.7, 129.4, 129.4, 129.1, 127.2, 124.0, 120.4, 118.1, 117.4, 116.9, 113.8, 66.3, 48.4, 29.4, 27.5. HRMS-ESI (m/z): calcd for C16H16NO [M + H]+, 238.1232; found, 238.1238.

4-Benzyl-1,2,3,4,4a,9,9a,10-octahydroacridine (2bf)

Yield: 90% (62.3 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.29 (dd, J = 10.5, 4.0 Hz, 2H), 7.22 (d, J = 7.2 Hz, 1H), 7.17 (d, J = 7.0 Hz, 2H), 6.98 (t, J = 7.5 Hz, 2H), 6.61 (t, J = 7.1 Hz, 1H), 6.42 (d, J = 7.8 Hz, 1H), 3.19 (dd, J = 6.8, 3.8 Hz, 1H), 2.98 (dd, J = 13.4, 5.5 Hz, 1H), 2.74 (dd, J = 9.2, 7.1 Hz, 2H), 2.51 (dd, J = 13.3, 9.1 Hz, 1H), 2.32–2.24 (m, 1H), 1.88 (dd, J = 7.1, 3.6 Hz, 1H), 1.72 (ddd, J = 14.1, 7.2, 3.6 Hz, 1H), 1.66–1.50 (m, 4H), 1.15 (ddd, J = 13.7, 8.0, 4.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 143.4, 141.0, 129.5, 129.1, 128.3, 126.7, 125.9, 119.9, 116.4, 113.3, 55.6, 41.0, 38.6, 31.5, 30.5, 30.2, 28.7, 20.4. HRMS-ESI (m/z): calcd for C20H24N [M + H]+, 278.1909; found, 278.1912.

7-Chloro-1,2,3,4,4a,9,9a,10-octahydroacridine (2bg)

Yield: 91% (50.3 mg) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 6.92 (d, J = 6.5 Hz, 2H), 6.42–6.35 (m, 1H), 3.54–3.49 (m, 1H), 2.89 (dd, J = 16.4, 5.6 Hz, 1H), 2.50 (dd, J = 16.4, 3.9 Hz, 1H), 1.96 (d, J = 3.8 Hz, 1H), 1.67 (ddd, J = 18.2, 8.7, 6.1 Hz, 4H), 1.47–1.36 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 142.5, 129.2, 126.4, 120.9, 120.6, 114.2, 50.0, 32.6, 32.5, 31.6, 27.1, 24.7, 20.6. HRMS-ESI (m/z): calcd for C13H17NCl [M + H]+, 222.1050; found, 222.1059.

Chiral Ir-1

Yield solid (mp: 252–256 °C), 1H NMR (400 MHz, CDCl3): δ 10.99 (d, J = 15.9 Hz, 1H), 9.32 (dd, J = 22.2, 6.6 Hz, 1H), 8.79 (dd, J = 43.2, 3.3 Hz, 1H), 7.96 (d, J = 6.4 Hz, 1H), 7.71 (s, 1H), 7.39–7.14 (m, 10H), 5.26–4.71 (m, 4H), 1.34 (d, J = 12.3 Hz, 15H). 13C NMR (100 MHz, CDCl3): δ 169.4, 168.9, 151.5, 151.3, 147.6, 146.7, 141.8, 140.9, 140.2, 140.0, 139.2, 138.4, 130.0, 129.6, 129.1, 129.0, 128.8, 128.6, 128.5, 128.3, 128.1, 128.0, 126.9, 126.6, 126.3, 88.2, 87.7, 79.2, 79.0, 72.1, 72.0, 53.6, 9.2, 9.0. HRMS-ESI (m/z): calcd for C31H35N3ClIr [M + H]+, 677.2141; found, 677.2149.

Chiral Ir-2

Yield solid. 1H NMR (400 MHz, CDCl3): δ 10.64 (s, 1H), 8.83 (s, 1H), 8.01 (s, 1H), 7.25 (d, J = 17.9 Hz, 13H), 4.93 (d, J = 81.0 Hz, 2H), 4.10 (s, 3H), 1.35 (d, J = 16.7 Hz, 16H). 13C NMR (100 MHz, CDCl3): δ 169.6, 163.7, 144.5, 143.8, 140.1, 138.9, 129.1, 128.4, 127.7, 126.6, 120.9, 112.1, 88.4, 87.5, 79.6, 71.6, 71.1, 58.9, 58.0, 10.0, 9.7. HRMS-ESI (m/z): calcd for C32H37N3OClIr [M + H]+, 707.2254; found, 707.2254.

Chiral Ir-3

Yield solid (mp: 241–253 °C). 1H NMR (400 MHz, CDCl3): δ 10.76 (s, 1H), 9.14 (d, J = 29.6 Hz, 1H), 8.56 (dd, J = 45.2, 5.1 Hz, 1H), 7.51–7.11 (m, 13H), 5.08–4.97 (m, 1H), 4.86 (dd, J = 41.5, 7.0 Hz, 1H), 2.43 (d, J = 24.5 Hz, 3H), 1.32 (d, J = 13.2 Hz, 15H). 13C NMR (100 MHz, CDCl3): δ 169.5, 169.0, 153.2, 152.9, 150.5, 150.3, 147.0, 146.2, 141.7, 140.9, 139.2, 139.1, 138.5, 130.6, 130.3, 129.1, 129.0, 128.9, 128.8, 128.7, 128.5, 128.5, 128.2, 126.8, 126.5, 126.2, 87.9, 87.5, 79.2, 78.9, 72.0, 9.2, 9.0. HRMS-ESI (m/z): calcd for C32H37N3ClIr [M + H]+, 691.2307; found, 691.2305.

Chiral Ir-4

Yield solid (mp: 272–278 °C). 1H NMR (400 MHz, CDCl3): δ 11.07 (d, J = 14.5 Hz, 1H), 9.50 (d, J = 39.3 Hz, 1H), 8.84 (dd, J = 68.1, 5.0 Hz, 1H), 7.84 (dd, J = 17.7, 5.4 Hz, 1H), 7.49–7.05 (m, 12H), 5.16–5.02 (m, 1H), 4.99–4.84 (m, 1H), 1.37 (d, J = 13.1 Hz, 15H). 13C NMR (100 MHz, CDCl3): δ 168.8, 168.3, 152.7, 152.2, 148.6, 148.5, 148.1, 147.7, 141.5, 140.8, 139.0, 138.4, 130.5, 130.2, 129.1, 128.8, 128.6, 128.5, 128.4, 126.9, 126.5, 126.3, 88.4, 88.0, 79.4, 79.0, 72.2, 72.1, 9.3, 9.1. HRMS-ESI (m/z): calcd for C31H34N3Cl2Ir [M + H]+, 711.1761; found, 711.1759.

Chiral Ir-5

Yield solid (mp: 196–208 °C). 1H NMR (400 MHz, CDCl3): δ 11.23 (s, 1H), 9.37 (d, J = 7.8 Hz, 1H), 8.46 (dd, J = 35.0, 8.2 Hz, 2H), 7.96 (d, J = 7.7 Hz, 1H), 7.88–7.82 (m, 1H), 7.73 (t, J = 6.8 Hz, 1H), 7.38–7.18 (m, 13H), 5.28 (d, J = 10.0 Hz, 1H), 5.04 (d, J = 10.0 Hz, 1H), 1.34 (s, 15H). 13C NMR (100 MHz, CDCl3): δ 169.4, 147.5, 145.6, 141.7, 139.7, 138.2, 132.2, 130.7, 130.2, 130.1, 129.2, 129.2, 128.6, 128.5, 128.5, 128.0, 126.4, 122.8, 88.0, 79.1, 71.0, 9.4. HRMS-ESI (m/z): calcd for C35H37N3ClIr [M + H]+, 727.2308; found, 727.2305.