Enantioselective Synthesis of Tetrahydroquinolines from 2

Sep 26, 2018 - A new asymmetric protocol for the synthesis of chiral tetrahydroquinolines from 2-aminochalcones via a two-step one-pot consecutive pro...
2 downloads 0 Views 773KB Size
Download PDF
Article pubs.acs.org/joc

Cite This: J. Org. Chem. 2018, 83, 12486−12495

Enantioselective Synthesis of Tetrahydroquinolines from 2‑Aminochalcones via a Consecutive One-Pot Reaction Catalyzed by Chiral Phosphoric Acid Do Young Park, So Young Lee, Jiye Jeon, and Cheol-Hong Cheon* Department of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea

Downloaded via UNIV OF SUNDERLAND on October 19, 2018 at 09:29:16 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: A new asymmetric protocol for the synthesis of chiral tetrahydroquinolines from 2-aminochalcones via a twostep one-pot consecutive process (cyclization/asymmetric reduction) has been developed using chiral phosphoric acid as the sole catalyst. 2-Aminochalcones were converted into the corresponding quinolines through chiral phosphoric acid-catalyzed dehydrative cyclization, and the resultant quinolines were subsequently reduced to the chiral tetrahydroquinolines via chiral phosphoric acid-catalyzed asymmetric reduction with Hantzsch ester. Various 2-aminochalcones could be applicable to this protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities. Furthermore, the utility of this protocol has been successfully demonstrated in the highly efficient synthesis of estrogen receptor modulator.

■

INTRODUCTION The combination of more than two catalytic transformations in one-pot without any isolation of intermediates can significantly increase synthetic efficiency in the preparation of optically active compounds.1 Accordingly, the development of novel methods based on this consecutive one-pot approach has drawn much attention from the synthetic community.2 However, most of the reported consecutive one-pot reactions involve the use of multiple catalytic systems, often resulting in poor compatibility between the catalytic components. A possible solution to this problem is a one-pot protocol featuring a single catalyst with mechanistically distinct modes of activation. However, there are a very limited number of reports on the use of such a strategy in the literature,3,4 and thus, further research and development would be required to establish novel asymmetric transformations via consecutive one-pot reactions catalyzed by single catalysts with different modes of activation. Following the seminal reports by Akiyama and Terada on the catalytic asymmetric transformations with chiral phosphoric acid,5 chiral phosphoric acid catalysis has become one of the most popular areas of research in asymmetric catalysis.6 In particular, since chiral phosphoric acid exhibits strong Brønsted acidity, numerous asymmetric transformations have been developed by exploiting this feature for the enantioselective activation of electrophiles via protonation. However, © 2018 American Chemical Society

most of the previous approaches have focused on the development of single asymmetric transformations, and there have been only limited examples of the catalytic enantioselective one-pot transformations including cascade reactions with chiral phosphoric acid.7 Furthermore, most of the previous one-pot protocols developed with chiral phosphoric acid have been developed using the combination of chiral phosphoric acid catalyst with different catalytic systems. Herein, we present a novel protocol for the enantioselective synthesis of chiral tetrahydroquinolines from 2-aminochalcones via consecutive one-pot catalysis using chiral phosphoric acid as the sole catalyst. Chiral phosphoric acid-catalyzed dehydrative cyclization of 2-aminochalcones provided the corresponding quinolines, and the resulting quinolines could be enantioselectively reduced to optically pure tetrahydroquinolines by the chiral phosphoric acid-asymmetric reduction with Hantzsch ester. A diverse range of 2-aminochalcones were applicable to this consecutive one-pot protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities. Furthermore, this protocol was successfully applied to the highly efficient synthesis of an estrogen receptor modulator. Received: July 6, 2018 Published: September 26, 2018 12486

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry

■

RESULTS AND DISCUSSION Chiral tetrahydroquinoline motifs have been found in various biologically active compounds, pharmaceuticals, and natural products. Accordingly, the development of efficient synthetic protocols for optically active tetrahydroquinolines has garnered considerable research interest.8−10 Owing to the utility of consecutive one-pot protocols, there are several examples of the one-pot synthesis of optically active tetrahydroquinolines, wherein the construction of the quinoline scaffolds and the asymmetric reduction of the resulting quinolines are performed in tandem.11 However, these one-pot protocols rely on the combination of two different catalyst systems: one for the preparation of the parent quinoline scaffolds and the other for enantioselective reduction of the resulting quinolines into tetrahydroquinolines. Thus, careful optimization of the reaction conditions is necessary to mitigate the problems associated with the poor compatibility between the two catalytic systems (Scheme 1a).

catalyzed isomerization of the double bond in 1 followed by condensation reaction, and 2 could be enantioselectively reduced to the optically active 2-substituted tetrahydroquinolines 4 through the chiral phosphoric acid-catalyzed enantioselective reduction (Scheme 1b). On the basis of this idea, we first explored the synthesis of quinolines 2 from 2-aminochalcones 1 using a chiral phosphoric acid as the catalyst (Table 1). It was found that Table 1. Investigation of Reaction Parameters for Dehydrative Cyclization of 1a to 2a with Phosphoric Acid 3

Scheme 1. Comparison of Previous Works and Our Work on the Asymmetric Synthesis of Tetrahydroquinolines through Consecutive One-Pot Procedures

entry

catalyst

solvent

T (°C)

t (h)

yield (%)a

1 2 3 4 5 6 7 8 9

− 3a 3b 3c 3d 3b 3b 3a 3c

ClCH2CH2Cl ClCH2CH2Cl ClCH2CH2Cl ClCH2CH2Cl ClCH2CH2Cl toluene toluene toluene toluene

80 80 80 80 80 80 110 110 110

48 12 12 12 12 12 12 12 24

trace 63 76 45 34 95 >99 (99)a >99 (99)b >99 (99)b

a

Yield of 2a was determined by 1H NMR analysis of the crude mixture after 12 h. bIsolated yield of 2a.

chiral phosphoric acid 3 effectively catalyzed the cyclization of 2-aminochalcones 1 into the corresponding quinolines 2. The desired quinoline product 2a was obtained in low yield in the absence of chiral phosphoric acid after 48 h, while 2a was obtained in 63% yield with 10 mol % of phosphoric acid 3a. Interestingly, the steric bulk and the nucleophilicity of the conjugate base of 3 played a considerable role in this transformation; steric bulky phosphoric acid 3c and less nucleophilic phosphoramide 3d displayed lower reactivities and provided 2a in 45% and 34%, respectively (entries 4 and 5).17,18 Changing solvent from 1,2-dichloroethane (DCE) to toluene exerted a beneficial influence on the formation of 2a; the reaction in toluene afforded 2a in 95% yield (entry 6). When the reaction temperature was increased to 110 °C, 2a was obtained in a quantitative yield (entry 7). Furthermore, under these conditions, other phosphoric acids, 3a and 3c, also provided the desired quinoline 2a in quantitative yields although a long reaction time was needed for steric bulky phosphoric acid 3c to go to completion (entries 8 and 9). With these results in hand, we next investigated the reaction parameters for the preparation of tetrahydroquinolines 4 from 1 via a one-pot transformation (Table 2).18 When a mixture of 1a and 3b was warmed to 110 °C in the presence of Hantzsch ester 5 in toluene, rather unexpectedly, tetrahydroquinoline 4a was obtained in 45% yield with 92% ee, and 1a remained unreacted in the reaction mixture even after a long time (entry 1). These results strongly indicated that Hantzsch ester 5 would interfere with the formation of quinoline 2a from 1a.

Dehydrative cyclization of 2-aminochalcones 1 is one of the most straightforward protocols for the construction of 2substituted quinolines 2.12−14 However, in general, the conversion of 2-aminochalcones 1 to quinolines 2 does not occur, because 1 exists in the stable (E)-configuration, where the amino group cannot approach the carbonyl group to undergo the condensation reaction.15 Thus, several protocols have been developed by exploiting the conversion of the stable but unreactive (E)-configuration into the unstable but reactive (Z)-configuration using various olefinic isomerization methods.12−14 Among the various methods, we have noticed that this transformation would be accomplished in the presence of strong Brønsted acid via acid-catalyzed isomerization of the double bond.14 Considering the fascinating reactivity of chiral phosphoric acid as a strong Brønsted acid6 with the combination of these previous examples,14 we envisioned that 2-aminochalcones 1 could be converted to the corresponding tetrahydroquinolines 4 in one-pot using chiral phosphoric acid as the sole catalyst;16 1 could be converted into the corresponding quinolines 2 via chiral phosphoric acid12487

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry Table 2. Optimization of Reaction Conditions

entry

catalyst

T (°C)

t (h)

yield (%)a

ee (%)b

1c,d 2d 3 4 5 6 7e 8f 9g

3b 3b 3b 3a 3c 3c 3c 3c 3c

80 80 80 80 80 25 25 25 25

36 1 1 1 1 1 1 1 48

45 >99 >99 >99 >99 >99 >99 >99 86

92 92 96 36 98 99 99 99 98

Isolated yield of 4a. bEnantiomeric excess (ee) was determined by chiral HPLC analysis. cA mixture of 1a, 3b, and 5 was treated at 110 °C. Without 4 Å molecular sieves. eWith 5 mol % 3c. fWith 3 mol % 3c. gWith 1 mol % 3c.

a

d

Consequently, we attempted to develop an alternative consecutive one-pot protocol. Treatment of 1a with 3b in toluene at 110 °C afforded quinoline 2a. Upon complete consumption of 1a, Hantzsch ester 5 was added to the reaction mixture, which was then subjected to enantioselective reduction at 80 °C. To our delight, the yield of 4a was significantly increased without loss of enantioselectivity (entry 2). In addition, molecular sieves were found to have a slightly beneficial influence on this transformation (entries 2 and 3). When the asymmetric reduction reaction was performed in the presence of 4 Å molecular sieves, the enantioselectivity of 4a increased from 92% ee to 96% ee. (entry 3). We further explored other phosphoric acids bearing different substituents at the 3,3′-positions in the asymmetric reduction reaction (entries 3−5). Delightfully, the enantioselectivity of 4a could be further improved with 3c bearing 2,4,6-tris(isopropyl)phenyl substituents at the 3,3′-positions (entry 5). Furthermore, the enantioselectivity of 4a could be further improved to 99% ee when the reaction was performed at room temperature (entry 6). The catalyst loading could be decreased to 1 mol % without any significant decrease in enantioselectivity, although a longer time was required for completion of the reaction (entries 6−9). Having established the optimized reaction conditions, we investigated the substrate scope of 2-aminochalcones 1 in this transformation (Table 3). Various 2-aminochalcone derivatives were applicable to this protocol, and the desired tetrahydroquinoline products 4 were obtained in excellent yields and with excellent enantioselectivities (entries 1−8). The electronic effect of the aryl group (R1) in 2-aminochalcones 1 had little effect on the efficiency of this transformation, while the steric bulkiness of the aryl group exerted a deleterious effect on the yield of the tetrahydroquinoline 4. 2-Aminochalcone 1g, having an ortho-substituent on the phenyl ring, provided the desired product 4g in much lower yield, although there was no considerable reduction in enantioselectivity (entry 7). 2Aminochalcone derivatives 1 bearing fused aromatics and heteroaromatics were amenable to this protocol, and the desired tetrahydroquinolines 4 were obtained in excellent yields (entries 9−12). We then investigated the effect of the substituent on the 2aminophenyl ring in the 2-aminochalcone derivatives 1 (entries 13−18). In all cases, the desired tetrahydroquinoline

Table 3. Substrate Scope

entry

product (4)

R1

R2

t (h)

yield (%)a

1 2 3 4 5 6 7d 8 9 10 11 12 13 14 15 16 17 18 19 20 21e

4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 4k 4l 4m 4n 4o 4p 4q 4r 4s 4t 4a

Ph 4-MeOC6H4 4-MeC6H4 4-FC6H4 4-ClC6H4 4-BrC6H4 2-MeC6H4 3-MeC6H4 1-naphthyl 2-naphthyl 2-furyl 2-thienyl Ph Ph Ph Ph Ph 4-MeOC6H4 methyl isopropyl Ph

H H H H H H H H H H H H 6-F 6-Cl 6-Br 6-MeO 7-Br 6-MeO H H H

1 1 1 4 4 1 24 2 24 2 1 2 1 1 2 12 12 12 5 5 3

99 98 97 95 99 99 43 97 98 99 99 99 99 78 99 99 92 98 73 71 99

ee (%)b,c 99 99 99 98 98 99 99 99 99 98 97 98 98 98 99 99 99 99 94 75 99

(S) (S) (S) (S) (S) (S) (S) (S) (S) (S) (S) (S) (S) (S) (S)

(S) (R) (S)

a

Isolated yield of 4. bEnantiomeric excess (ee) was determined by a chiral HPLC analysis. cAbsolute configuration of 4 was determined by comparison of its optical rotation value with that reported in the literature. dFormation of quinoline 2 from 1 was carried out for 40 h. e 10 mmol of 1a with 2 mol % of 3c.

products 4 were obtained in excellent yields and with excellent enantioselectivities, regardless of the electronic nature of the substituent and its position on the 2-aminophenyl ring. Furthermore, alkyl 2-aminostyryl ketone derivatives were found to be applicable to this protocol, but both the enantioselectivity and yields were lower than those achieved with their aromatic analogues (entries 19−20). Finally, we 12488

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry

tetrahydroquinoline 4r. Without isolation of 4r, the second reductive amination with unprotected 4-hydroxybenzaldehyde (7) was attempted by adding the latter to the reaction mixture. Since reductive amination of 7 and 4r with 3c provided the desired product (S)-9 in low yield, a catalytic amount of trifluoroacetic acid (TFA) was added to the crude mixture to further promote the second reductive amination. To our delight, under these conditions, the reductive amination proceeded smoothly to provide (S)-9 in 81% overall yield after only one separation step, with perfect enantioselectivity. It should be noted that this new approach considerably improved the efficiency of the synthesis of estrogen modulator receptor (S)-10 as compared to the previous approaches. We could prepare this compound from 2-aminochalcone 1r in 81% yield, with 99% ee, by employing a single column separation,21 while the same compound was previously prepared from quinoline 2r via quinoline reduction, N-alkylation, and debenzylation steps.20

established that this reaction could be performed at the gram scale (10 mmol scale), even with only 2 mol % loading of 3c, without any loss of efficiency (entry 21). The absolute stereochemistry of tetrahydroquinolines 4 was assigned as (S) by comparing the optical rotations of these products with the values reported in the literature.19 To further demonstrate the utility of this protocol, we applied it to the synthesis of compound 10, an estrogen receptor modulator (Scheme 2).20 Reductive amination of the Scheme 2. Asymmetric Synthesis of an Estrogen Receptor Modulator (S)-10

■

CONCLUSIONS In summary, we have developed a highly efficient two-step, consecutive one-pot protocol for the asymmetric synthesis of chiral tetrahydroquinolines from 2-aminochalcones using chiral phosphoric acids as the sole catalyst. 2-Aminochalcones could be converted into the corresponding quinolines through a chiral phosphoric acid-catalyzed E/Z isomerization of a double bond followed by condensation, and the resulting quinolines were reduced to the optically active tetrahydroquinolines by chiral phosphoric acid catalyzed asymmetric reduction. A wide range of 2-aminochalcones were compatible with this protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities. Furthermore, the utility of this protocol was unambiguously demonstrated by extending it to the asymmetric synthesis of a key intermediate for the preparation of an estrogen modulator inhibitor. Further development of enantioselective one-pot catalysis with chiral phosphoric acid catalysts are under investigation by our group, and the results will be reported in due course.

■

EXPERIMENTAL SECTION

General Methods. All reactions were carried out in an oven-dried glassware in an open flask unless otherwise noted. Except as otherwise indicated, all reactions were magnetically stirred and monitored by analytical thin layer chromatography (TLC) using precoated silica gel glass plates (0.25 mm) with F254 indicator. Visualization was accomplished by UV light (254 nm), with combination of potassium permanganate and/or phosphomolybdic acid solution as an indicator. Flash column chromatography was performed using silica gel 60 (230−400 mesh). Yields refer to chromatographically and spectroscopically pure compounds, unless otherwise noted. All commercial grade reagents and solvents were purchased from chemical suppliers and used without further purification unless otherwise noted. 2-Aminochalcones 1 were prepared from 2-nitrobenzaldehyde and the proper methyl ketones via aldol condensation followed by the reduction of a nitro group into an amino group reported in the literature.17,22 1H NMR and 13C NMR spectra were recorded on 500 and 125 MHz spectrometers, respectively. Tetramethylsilane (δH: 0.0 ppm) and a residual NMR solvent (CDCl3 (δC: 77.16 ppm)) were used as internal standards for 1H NMR and 13C NMR spectra, respectively. The proton spectra are reported as follows: δ (position of proton, multiplicity, coupling constant J, number of protons). Multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), p (quintet), h (septet), m (multiplet) and br (broad). High resolution mass spectra (HRMS) were recorded on quadrupole time-

resulting tetrahydroquinoline (S)-4r (entry 18, Table 3) with 4-(benzyloxy)benzaldehyde 6 in the presence of trifluoroacetic acid (TFA) afforded N-benzylated tetrahydroquinoline (S)-8 in 72% yield, with 99% ee. However, we encountered an unexpected difficulty in the preparation of compound 9, which was used as the key intermediate in the previous synthesis. Hydrogenolysis of the benzylic hydroxy group in (S)-8 using hydrogen gas with a palladium catalyst provided the desired compound (S)-9 only in 41% and 99% ee, and a considerable amount of tetrahydroquinoline 4r was obtained (43% yield and 99% ee) through hydrogenolysis of the N-benzyl moiety (Scheme 2a). Since the previous synthetic route20 gave a low yield of (S)9, we attempted to develop a more efficient strategy. Given the good functional group tolerance of our protocol, we attempted to develop a more streamlined route for the synthesis of (S)-9 by performing all the transformations in the same pot (Scheme 2b). Treatment of 2-aminochalcone 1r with chiral phosphoric acid 3c, followed by asymmetric reduction with Hantzsch ester 5 of the resulting quinoline 2r generated the desired 12489

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry

comparison of optical rotation reported in the literature.10b [α]D20 = −22.8 (c = 1.0, CHCl3, 94% ee) for (S)-isomer. (S)-2-(4-Fluorophenyl)-1,2,3,4-tetrahydroquinoline (4d). The product was obtained as colorless oil in 95% yield (43 mg) and 98% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.10b 1H NMR (500 MHz, CDCl3, ppm) δ 7.41−7.33 (m, 2H), 7.08−6.99 (m, 4H), 6.67 (td, J = 7.4, 1.1 Hz, 1H), 6.55 (d, J = 7.8 Hz, 1H), 4.43 (dd, J = 9.5, 3.2 Hz, 1H), 4.01 (br. s., 1H), 2.96−2.89 (m, 1H), 2.73 (dt, J = 16.5, 4.7 Hz, 1H), 2.12−2.07 (m, 1H), 2.02−1.91 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 163.2, 161.3, 144.7, 140.9, 140.6, 129.5, 128.2, 128.2, 127.1, 120.9, 117.5, 115.6, 115.4, 114.2, 55.1, 31.3, 26.4. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 13.7 min, tR (minor) = 27.3 min. [α]D20 = −46.5 (c = 1.0, CHCl3, 98% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.10b [α]D20 = −41.3 (c = 1.2, CHCl3, 97% ee) for (S)-isomer. (S)-2-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinoline (4e). The product was obtained as yellow oil in 99% yield (48 mg) and 98% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.33−7.31 (m, 4H), 7.04−6.98 (m, 2H), 6.67 (td, J = 7.4, 1.1 Hz, 1H), 6.55 (dd, J = 7.9, 0.8 Hz, 1H), 4.43 (dd, J = 9.2, 3.2 Hz, 1H), 4.02 (br. s., 1H), 2.94−2.88 (m, 1H), 2.72 (dt, J = 16.4, 4.9 Hz, 1H), 2.12−2.08 (m, 1H), 1.99−1.91 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.5, 143.5, 133.1, 129.5, 128.8, 128.0, 127.1, 120.9, 117.5, 114.2, 55.7, 31.1, 26.3. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 15.9 min, tR (minor) = 37.4 min. [α]D20= −26.3 (c = 1.0, CHCl3, 98% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −32.1 (c = 0.63, CHCl3, 93% ee) for (S)-isomer. (S)-2-(4-Bromophenyl)-1,2,3,4-tetrahydroquinoline (4f). The product was obtained as yellow solid in 99% yield (57 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.10b 1H NMR (500 MHz, CDCl3, ppm) δ 7.47 (d, J = 8.4 Hz, 2H), 7.32−7.22 (m, 2H), 7.06−6.96 (m, 2H), 6.67 (t, J = 7.3 Hz, 1H), 6.56 (d, J = 7.8 Hz, 1H), 4.42 (dd, J = 9.0, 3.1 Hz, 1H), 4.03 (br. s., 1H), 2.94−2.89 (m, 1H), 2.72 (dt, J = 16.3, 4.8 Hz, 1H), 2.15−2.06 (m, 1H), 2.01− 1.89 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.5, 144.0, 131.8, 129.4, 128.4, 127.1, 121.2, 120.9, 117.5, 114.2, 55.7, 31.0, 26.2. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 19.5 min, tR (minor) = 34.2 min. [α]D20 = −13.4 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.10b [α]D20 = −33.1 (c = 1.1, CHCl3, 97% ee) for (S)-isomer. (S)-2-(o-Tolyl)-1,2,3,4-tetrahydroquinoline (4g). The product was obtained as colorless oil in 43% yield (19 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:12) as an eluent. The spectroscopic data were in good agreement with the literature.10b 1H NMR (500 MHz, CDCl3, ppm) δ 7.55−7.49 (m, 1H), 7.25−7.15 (m, 3H), 7.06−7.00 (m, 2H), 6.67 (td, J = 7.4, 1.1 Hz, 1H), 6.58−6.54 (m, 1H), 4.69 (dd, J = 9.3, 3.2 Hz, 1H), 3.96 (br. s., 1H), 2.98−2.91 (m, 1H), 2.77 (dt, J = 16.3, 4.7 Hz, 1H), 2.39 (s, 3H), 2.14−2.09 (m, 1H), 1.98−1.88 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 145.2, 142.7, 134.9, 130.6, 129.4, 127.2, 127.0, 126.5, 126.1, 121.0, 117.2, 114.1, 52.3, 29.3, 26.7, 19.2. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 17.6 min, tR (minor) = 21.6

of-flight mass spectrometer (QTOF-MS) using electrospray ionization (ESI) as an ionization method. Enantioselectivity was determined by high performance liquid chromatography (HPLC) using a chiral column (0.46 cm × 250 mm) with 2-propanol/hexane as the eluent. Optical rotation was performed on automatic polarimeter. General Procedure for the Synthesis of 1,2,3,4-Tetrahydroquinoline Derivatives 4 (Table 3). A test tube equipped with a stirring bar was charged with (E)-2-aminochalcone derivative 1 (0.20 mmol; 1.0 equiv), catalyst 3c (0.010 mmol; 5 mol %). Then, toluene (2.0 mL) was added to the above mixture. The reaction mixture was stirred at 110 °C in an open flask and monitored by TLC. After complete consumption of compound 1, the reaction was cooled to room temperature. To the reaction mixture were added 4 Å molecular sieves (200 mg), Hantzsch ester (0.48 mmol; 2.4 equiv). The reaction mixture was stirred at 25 °C in an open flask and monitored by TLC. After complete consumption of quinoline 2, the reaction mixture was filtered. The filtrate was concentrated and purified by column chromatography on silica gel to provide the desired product 4. (S)-2-Phenyl-1,2,3,4-tetrahydroquinoline (4a). The product was obtained as pale yellow oil in 99% yield (41 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.45−7.36 (m, 4H), 7.35−7.29 (m, 1H), 7.08−7.00 (m, 2H), 6.68 (td, J = 7.4, 1.0 Hz, 1H), 6.57 (d, J = 7.8 Hz, 1H), 4.46 (dd, J = 9.4, 3.3 Hz, 1H), 4.06 (br. s., 1H), 2.99−2.93 (m, 1H), 2.77 (dt, J = 16.3, 4.7 Hz, 1H), 2.20−2.11 (m, 1H), 2.08−1.97 (m, 1H); 13 C NMR (125 MHz, CDCl3, ppm) δ 144.9, 144.8, 129.4, 128.7, 127.6, 127.0, 126.7, 121.0, 117.3, 114.1, 56.4, 31.1, 26.5. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 15.7 min, tR (minor) = 20.5 min. [α]D20 = −28.4 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −25.7 (c = 1.1, CHCl3, 95% ee) for (S)-isomer. (S)-2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroquinoline (4b). The product was obtained as pale yellow oil in 98% yield (47 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.34−7.29 (m, 2H), 7.04−6.97 (m, 2H), 6.92−6.86 (m, 2H), 6.65 (td, J = 7.4, 1.1 Hz, 1H), 6.53 (dd, J = 8.3, 1.0 Hz, 1H), 4.39 (dd, J = 9.6, 3.1 Hz, 1H), 4.00 (br. s., 1H), 3.84−3.79 (m, 3H), 2.96−2.90 (m, 1H), 2.74 (dt, J = 16.3, 4.5 Hz, 1H), 2.13−2.04 (m, 1H), 2.02−1.92 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 159.1, 145.0, 137.0, 129.4, 127.8, 127.0, 121.0, 117.2, 114.1, 114.0, 55.8, 55.5, 31.2, 26.7. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 16.5 min, tR (minor) = 31.0 min. [α]D22 = −33.5 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −20.0 (c = 1.1, CHCl3, 95% ee) for (S)-isomer. (S)-2-(p-Tolyl)-1,2,3,4-tetrahydroquinoline (4c). The product was obtained as pale yellow oil in 97% yield (43 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.10b 1H NMR (500 MHz, CDCl3, ppm) δ 7.29 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 7.9 Hz, 2H), 7.04−6.99 (m, 2H), 6.65 (td, J = 7.4, 1.0 Hz, 1H), 6.54 (dd, J = 8.4, 0.9 Hz, 1H), 4.41 (dd, J = 9.5, 3.2 Hz, 1H), 4.02 (br. s., 1H), 2.96− 2.90 (m, 1H), 2.75 (dt, J = 16.3, 4.7 Hz, 1H), 2.36 (s, 3H), 2.15−2.07 (m, 1H), 2.04−1.93 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.9, 141.9, 137.2, 129.4, 129.4, 127.0, 126.6, 121.0, 117.2, 114.1, 56.1, 31.1, 26.6, 21.2. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 11.7 min, tR (minor) = 22.7 min. [α]D20 = −29.6 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)-configuration with 12490

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry min. [α]D18 = −39.3 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.10b [α]D20 = −33.8 (c = 1.0, CHCl3, 86% ee) for (S)-isomer. (S)-2-(m-Tolyl)-1,2,3,4-tetrahydroquinoline (4h). The product was obtained as pale yellow oil in 97% yield (43 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:12) as an eluent. The spectroscopic data were in good agreement with the literature.20b 1H NMR (500 MHz, CDCl3, ppm) δ 7.28−7.19 (m, 3H), 7.12 (d, J = 7.3 Hz, 1H), 7.06−6.98 (m, 2H), 6.67 (td, J = 7.4, 0.9 Hz, 1H), 6.55 (d, J = 7.6 Hz, 1H), 4.41 (dd, J = 9.6, 3.2 Hz, 1H), 4.03 (br. s., 1H), 2.98−2.91 (m, 1H), 2.76 (dt, J = 16.3, 4.7 Hz, 1H), 2.38 (s, 3H), 2.17−2.08 (m, 1H), 2.06−1.95 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.9, 138.4, 129.4, 128.6, 128.3, 127.4, 127.0, 123.8, 121.0, 117.2, 114.1, 56.4, 31.2, 26.7, 21.6. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 12.8 min, tR (minor) = 16.9 min. [α]D18 = −38.2 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.20b [α]D22 = +19.5 (c = 0.4, CHCl3, 82% ee) for (R)-isomer. (S)-2-(Naphthalen-1-yl)-1,2,3,4-tetrahydroquinoline (4i). The product was obtained as pale yellow oil in 98% yield (51 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 8.17 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.69 (d, J = 7.2 Hz, 1H), 7.59−7.51 (m, 2H), 7.48 (t, J = 7.7 Hz, 1H), 7.11−7.04 (m, 2H), 6.71 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 7.8 Hz, 1H), 5.30 (dd, J = 8.5, 3.3 Hz, 1H), 4.15 (br. s., 1H), 3.05−2.94 (m, 1H), 2.77 (dt, J = 16.3, 5.1 Hz, 1H), 2.39−2.29 (m, 1H), 2.25−2.14 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 145.0, 140.1, 134.0, 130.6, 129.5, 129.2, 127.9, 127.1, 126.3, 125.7, 125.7, 123.7, 122.9, 121.0, 117.3, 114.1, 52.2, 29.3, 26.3. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 23.1 min, tR (minor) = 41.2 min. [α]D22 = −128.3 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −65.6 (c = 0.58, CHCl3, 91% ee) for (S)-isomer. (S)-2-(Naphthalen-2-yl)-1,2,3,4-tetrahydroquinoline (4j). The product was obtained as pale yellow oil in 99% yield (52 mg) and 98% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.86−7.82 (m, 4H), 7.52 (dd, J = 8.5, 1.5 Hz, 1H), 7.51−7.46 (m, 2H), 7.07−7.01 (m, 2H), 6.69 (td, J = 7.4, 1.0 Hz, 1H), 6.60 (d, J = 7.9 Hz, 1H), 4.62 (dd, J = 9.3, 3.4 Hz, 1H), 4.16 (br. s., 1H), 3.00−2.94 (m, 1H), 2.78 (dt, J = 16.3, 4.7 Hz, 1H), 2.22−2.17 (m, 1H), 2.14−2.06 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.8, 142.3, 133.5, 133.1, 129.5, 128.5, 128.0, 127.8, 127.1, 126.3, 125.9, 125.2, 125.0, 121.1, 117.4, 114.2, 56.5, 31.1, 26.6. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 21.3 min, tR (minor) = 39.7 min. [α]D20 = −31.2 (c = 1.0, CHCl3, 98% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −20.6 (c = 0.6, CHCl3, 96% ee) for (S)-isomer. (S)-2-(Furan-2-yl)-1,2,3,4-tetrahydroquinoline (4k). The product was obtained as pale yellow oil in 99% yield (39 mg) and 97% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.37 (dd, J = 1.8, 0.7 Hz, 1H), 7.03−6.96 (m, 2H), 6.66 (td, J = 7.4, 1.0 Hz, 1H), 6.55 (d, J = 7.9 Hz, 1H), 6.33 (dd, J = 3.1, 1.9 Hz, 1H), 6.21 (d, J = 3.2 Hz, 1H), 4.54 (dd, J = 8.3, 3.4 Hz, 1H), 4.14 (br. s., 1H), 2.92−2.83 (m, 1H), 2.75 (dt, J = 16.3, 5.5 Hz,

1H), 2.26−2.18 (m, 1H), 2.18−2.10 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 157.1, 143.9, 141.8, 129.4, 127.0, 121.1, 117.7, 114.5, 110.3, 105.3, 49.8, 27.0, 25.7. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 15.4 min, tR (minor) = 17.3 min. [α]D20 = +37.5 (c = 1.0, CHCl3, 97% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = +25.8 (c = 1.0, CHCl3, 90% ee) for (S)-isomer. (S)-2-(Thiophen-2-yl)-1,2,3,4-tetrahydroquinoline (4l). The product was obtained as pale yellow oil in 99% yield (43 mg) and 98% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:15) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.23 (dd, J = 5.0, 1.2 Hz, 1H), 7.04−6.96 (m, 4H), 6.68 (td, J = 7.4, 1.0 Hz, 1H), 6.55 (d, J = 7.9 Hz, 1H), 4.76 (dd, J = 9.2, 3.2 Hz, 1H), 4.17 (br. s., 1H), 2.99−2.89 (m, 1H), 2.79 (dt, J = 16.3, 4.9 Hz, 1H), 2.25−2.20 (m, 1H), 2.14−2.05 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 149.0, 144.1, 129.4, 127.0, 126.8, 124.2, 123.7, 121.0, 117.8, 114.4, 52.1, 31.9, 26.3. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 23.8 min, tR (minor) = 32.0 min. [α]D20 = −11.9 (c = 1.0, CHCl3, 98% ee). The absolute configuration was determined as (S)configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −11.2 (c = 1.0, CHCl3, 90% ee) for (S)-isomer. (S)-6-Fluoro-2-phenyl-1,2,3,4-tetrahydroquinoline (4m). The product was obtained as pale yellow oil in 99% yield (45 mg) and 98% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.42−7.33 (m, 4H), 7.32−7.27 (m, 1H), 6.77−6.69 (m, 2H), 6.50−6.44 (m, 1H), 4.39 (dd, J = 9.5, 3.1 Hz, 1H), 3.95 (br. s., 1H), 2.95−2.89 (m, 1H), 2.72 (dt, J = 16.6, 4.7 Hz, 1H), 2.14−2.08 (m, 1H), 2.02−1.94 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 156.6, 154.7, 144.7, 141.1, 128.7, 127.7, 126.7, 122.3, 122.2, 115.7, 115.5, 114.8, 114.7, 113.6, 113.4, 56.5, 30.8, 26.7. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 14.7 min, tR (minor) = 22.9 min. [α]D20 = −54.2 (c = 1.0, CHCl3, 98% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −52.5 (c = 0.71, CHCl3, 96% ee) for (S)-isomer. (S)-6-Chloro-2-phenyl-1,2,3,4-tetrahydroquinoline (4n). The product was obtained as pale yellow oil in 78% yield (38 mg) and 98% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:12) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.40−7.33 (m, 4H), 7.33−7.28 (m, 1H), 7.00−6.93 (m, 2H), 6.46 (d, J = 8.2 Hz, 1H), 4.43 (dd, J = 9.2, 3.3 Hz, 1H), 4.06 (br. s., 1H), 2.91−2.85 (m, 1H), 2.70 (dt, J = 16.5, 4.9 Hz 1H), 2.17−2.07 (m, 1H), 2.03−1.91 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.5, 143.4, 129.0, 128.8, 127.7, 126.8, 126.6, 122.5, 121.6, 115.0, 56.3, 30.6, 26.3. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 19.5 min, tR (minor) = 40.2 min. [α]D20 = −5.1 (c = 0.8, CHCl3, 98% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = −9.2 (c = 1.0, CHCl3, 96% ee) for (S)-isomer. (S)-6-Bromo-2-phenyl-1,2,3,4-tetrahydroquinoline (4o). The product was obtained as pale yellow oil in 99% yield (57 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. The spectroscopic data were in good agreement with the literature.11c 1H NMR (500 MHz, CDCl3, ppm) δ 7.39−7.33 (m, 4H), 7.32−7.28 (m, 1H), 7.14−7.06 (m, 2H), 6.42 (d, J = 8.4 Hz, 1H), 4.43 (dd, J = 9.1, 3.3 Hz, 1H), 4.07 (br. s., 1H), 2.91−2.84 (m, 1H), 2.70 (dt, J = 16.5, 4.9 Hz, 1H), 2.16−2.07 (m, 1H), 2.02−1.90 (m, 1H); 13C NMR (125 12491

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry MHz, CDCl3, ppm) δ 144.5, 143.8, 131.8, 129.7, 128.8, 127.7, 126.6, 123.1, 115.5, 108.6, 56.2, 30.5, 26.2. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2propanol = 90:10, flow rate = 0.8 mL/min, λ = 254 nm), tR (major) = 13.5 min, tR (minor) = 25.1 min. [α]D18 = −19.5 (c = 1.0, CHCl3, 99% ee). The absolute configuration was determined as (S)configuration with comparison of optical rotation reported in the literature.11c [α]D27 = +41.6 (c = 0.8, CHCl3, 99% ee) for (R)-isomer. (S)-6-Methoxy-2-phenyl-1,2,3,4-tetrahydroquinoline (4p). The product was obtained as pale yellow oil in 99% yield (47 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. 1H NMR (500 MHz, CDCl3, ppm) δ 7.42−7.38 (m, 2H), 7.38−7.33 (m, 2H), 7.31−7.27 (m, 1H), 6.67−6.60 (m, 2H), 6.51 (d, J = 8.5 Hz, 1H), 4.37 (dd, J = 9.6, 3.1 Hz, 1H), 3.84 (br. s., 1H), 3.75 (s, 3H), 2.97− 2.91 (m, 1H), 2.74 (dt, J = 16.6, 4.6 Hz, 1H), 2.15−2.07 (m, 1H), 2.05−1.94 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 152.0, 145.0, 139.1, 128.7, 127.5, 126.7, 122.3, 115.3, 114.8, 113.2, 56.7, 56.0, 31.3, 27.0. HRMS (ESI) calcd for C16H18NO [M + H]+ 240.1383, found 240.1381. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 15.8 min, tR (minor) = 21.7 min. [α]D20 = −19.3 (c = 1.0, CHCl3, 99% ee). (S)-7-Bromo-2-phenyl-1,2,3,4-tetrahydroquinoline (4q). The product was obtained as pale yellow oil in 92% yield (53 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:10) as an eluent. 1H NMR (500 MHz, CDCl3, ppm) δ 7.39−7.35 (m, 4H), 7.33−7.28 (m, 1H), 6.85 (d, J = 7.9 Hz, 1H), 6.75 (dd, J = 7.9, 1.8 Hz, 1H), 6.68 (d, J = 1.8 Hz, 1H), 4.45 (dd, J = 9.0, 3.4 Hz, 1H), 4.11 (br. s., 1H), 2.86− 2.79 (m, 1H), 2.67 (dt, J = 16.3, 5.0 Hz, 1H), 2.16−2.08 (m, 1H), 2.02−1.90 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 146.0, 144.4, 130.7, 128.8, 127.7, 126.6, 120.2, 119.8, 119.8, 116.3, 56.0, 30.6, 25.9. HRMS (ESI) calcd for C15H15BrN [M + H]+ 288.0382, found 288.0384. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.8 mL/min, λ = 254 nm), tR (major) = 12.4 min, tR (minor) = 17.3 min. [α]D20 = −16.6 (c = 1.0, CHCl3, 99% ee). (S)-6-Methoxy-2-(4-methoxyphenyl)-1,2,3,4-tetrahydroquinoline (4r). The product was obtained as pale yellow oil in 98% yield (53 mg) and 99% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:5) as an eluent. The spectroscopic data were in good agreement with the literature.20b 1 H NMR (500 MHz, CDCl3, ppm) δ 7.32 (d, J = 8.7 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 6.66−6.59 (m, 2H), 6.49 (d, J = 8.4 Hz, 1H), 4.31 (dd, J = 9.8, 2.8 Hz, 1H), 3.81 (s, 3H), 3.77 (br. s., 1H), 3.75 (s, 3H), 2.98−2.91 (m, 1H), 2.73 (dt, J = 16.5, 4.4 Hz, 1H), 2.11−2.03 (m, 1H), 2.02−1.91 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 159.0, 152.0, 139.2, 137.1, 127.8, 122.3, 115.2, 114.8, 114.0, 113.1, 56.2, 56.0, 55.5, 31.4, 27.1. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 16.0 min, tR (minor) = 25.7 min. [α]D18 = −21.2 (c = 0.8, CHCl3, 99% ee). The absolute configuration was determined as (S)-configuration with comparison of optical rotation reported in the literature.20b [α]D22 = +12.9 (c = 1.1, CHCl3, 84% ee) for (R)-isomer. (R)-2-Methyl-1,2,3,4-tetrahydroquinoline (4s). The product was obtained as pale yellow oil in 73% yield (22 mg) and 94% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:5) as an eluent. The spectroscopic data were in good agreement with the literature.11d 1H NMR (500 MHz, CDCl3, ppm) δ 7.01−6.92 (m, 2H), 6.61 (t, J = 7.3 Hz, 1H), 6.48 (d, J = 8.2 Hz, 1H), 3.70 (br. s., 1H), 3.44−3.38 (m, 1H), 2.91−2.80 (m, 1H), 2.78−2.68 (m, 1H), 1.98−1.90 (m, 1H), 1.64−1.56 (m, 1H), 1.22 ppm (d, J = 6.3 Hz, 3H); 13C NMR (125 MHz, CDCl3, ppm) δ 144.9, 129.4, 126.8, 121.2, 117.1, 114.1, 47.3, 30.3, 26.7, 22.8. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OJ-H column (hexanes:2-propanol = 99:1, flow rate = 0.7 mL/min, λ = 254 nm), tR (minor) = 21.8 min, tR (major) = 27.3 min. [α]D20 = +34.1 (c = 0.8, CHCl3, 94% ee). The absolute configuration was

determined as (R)-configuration with comparison of optical rotation reported in the literature.11d [α]D25 = +49.2 (c = 0.71, CHCl3, 84% ee) for (R)-isomer. (S)-2-Isopropyl-1,2,3,4-tetrahydroquinoline (4t). The product was obtained as pale yellow oil in 71% yield (25 mg) and 75% ee after purification by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:15) as an eluent. 1H NMR (500 MHz, CDCl3, ppm) δ 7.00−6.93 (m, 2H), 6.60 (t, J = 7.3 Hz, 1H), 6.49 (d, J = 7.8 Hz, 1H), 3.77 (br. s., 1H), 3.08−3.01 (m, 1H), 2.86−2.70 (m, 2H), 1.96−1.88 (m, 1H), 1.77−1.61 (m, 2H), 1.01 (d, J = 6.9 Hz, 3H), 0.98 ppm (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3, ppm) δ 145.2, 129.3, 126.8, 121.6, 116.8, 114.1, 57.4, 32.7, 26.8, 24.7, 18.7, 18.4. HRMS (ESI) calcd for C12H18N [M + H]+ 176.1434, found 176.1432. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 95:5, flow rate = 0.6 mL/min, λ = 254 nm), tR (major) = 9.1 min, tR (minor) = 10.3 min. [α]D22 = +38.9 (c = 0.8, CHCl3, 75% ee). Synthesis of Compound (S)-8. A test tube equipped with a stirring bar was charged with tetrahydroquinoline derivative (S)-4r (0.20 mmol; 1.0 equiv), 4-(benzyloxy)benzaldehyde 6 (0.70 mmol; 3.5 equiv), Hantzsch ester (0.50 mmol; 2.5 equiv), and 4 Å molecular sieves (200 mg). Then, toluene (2.0 mL) was added to the above mixture. To the above mixture was added trifluoroacetic acid (7.7 μL, 50 mol %) dropwise via a syringe at room temperature. The reaction mixture was stirred for 14 h at 60 °C and monitored by TLC. After complete consumption of compound (S)-4r, the reaction mixture was quenched with saturated aqueous sodium bicarbonate. The crude mixture was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography on silica using a mixture of ether, CH2Cl2 and hexanes (1:5:15) as an eluent to provide the desired product (S)-8 as pale yellow oil in 72% yield (67 mg) and 99% ee. The spectroscopic data were in good agreement with the literature.20c 1H NMR (500 MHz, CDCl3, ppm) δ 7.45−7.30 (m, 5H), 7.11 (dd, J = 12.3, 8.6 Hz, 4H), 6.91 (d, J = 8.1 Hz, 2H), 6.83 (d, J = 8.1 Hz, 2H), 6.67−6.59 (m, 2H), 6.48 (d, J = 8.9 Hz, 1H), 5.04 (s, 2H), 4.63−4.50 (m, 2H), 4.14 (d, J = 17.1 Hz, 1H), 3.79 (s, 3H), 3.73 (s, 3H), 2.66−2.58 (m, 2H), 2.26−2.20 (m, 1 H), 2.08− 1.98 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 158.6, 157.8, 150.5, 139.9, 137.2, 136.4, 131.3, 128.7, 128.1, 127.9, 127.6, 123.6, 115.1, 115.0, 113.9, 112.6, 111.3, 70.2, 60.7, 55.9, 55.4, 52.7, 30.1, 24.3. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 1.0 mL/min, λ = 220 nm), tR (major) = 13.7 min, tR (minor) = 22.2 min. Synthesis of Compound (S)-9 from Compound (S)-8 via Debenzylation. A test tube equipped with a stirring bar was charged with (S)-8 (0.10 mmol; 1.0 equiv), palladium on carbon (11 mg). Then, methanol (1.0 mL) was added to the above mixture. The reaction mixture was stirred at room temperature under a hydrogen atmosphere and monitored by TLC. After complete consumption of compound (S)-8, the reaction mixture was filtered through Celite, and washed with ethyl acetate. Then, the filtrate was concentrated, and the crude mixture was purified by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:5) as an eluent to provide the product (S)-9 as pale yellow oil in 41% yield (15 mg) and 99% ee. At the same time, (S)-4r was obtained as pale yellow oil in 43% yield (12 mg) and 99% ee via the N-debenzylation. Compound (S)-9: 1H NMR (500 MHz, CDCl3, ppm) δ 7.09 (dd, J = 12.1, 8.5 Hz, 4H), 6.88−6.80 (m, 2H), 6.79−6.72 (m, 2H), 6.66−6.59 (m, 2H), 6.51− 6.44 (m, 1H), 4.85 (br. s., 1H), 4.60−4.50 (m, 2H), 4.12 (d, J = 16.9 Hz, 1H), 3.79 (s, 3H), 3.74 (s, 3H), 2.69−2.54 (m, 2H), 2.29−2.16 (m, 1H), 2.08−1.97 (m, 1H); 13C NMR (125 MHz, CDCl3, ppm) δ 158.6, 154.4, 150.5, 139.9, 136.4, 131.2, 127.9, 127.8, 123.6, 115.5, 115.1, 113.9, 112.6, 111.4, 60.7, 55.9, 55.4, 52.7, 30.1, 24.3. HRMS (ESI) calcd for C24H26NO3 [M + H]+ 376.1907, found 376.1906. Enantiomeric excess (ee) was determined by HPLC with a Chiralcel OD-H column (hexanes:2-propanol = 90:10, flow rate = 0.6 mL/min, λ = 220 nm), tR (major) = 19.8 min, tR (minor) = 37.3 min. [α]D18 = +10.286 (c = 1.0, CHCl3, 99% ee). 12492

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry Sequential One-Pot Synthesis of Compound (S)-9. A test tube equipped with a stirring bar was charged with 1r (0.20 mmol; 1.0 equiv), catalyst 3c (0.010 mmol; 5.0 mol %). Then, toluene (2.0 mL) was added to the above mixture. The reaction mixture was stirred at 110 °C in an open flask and monitored by TLC. After complete consumption of compound 1r, the reaction was cooled to room temperature. To the reaction mixture were added 4 Å molecular sieves (200 mg), Hantzsch ester (0.48 mmol; 2.4 equiv). The reaction mixture was stirred at 25 °C in an open flask and monitored by TLC. After complete consumption of quinoline 2r, 4-hydroxybenzaldehyde 7 (0.7 mmol; 3.5 equiv), Hantzsch ester (0.5 mmol; 2.5 equiv), 4 Å molecular sieves (100 mg), additional toluene (1 mL) were added. To a solution at room temperature was added trifluoroacetic acid (7.7 μL, 50 mol %) dropwise via a syringe. The reaction mixture was stirred for 14 h at 60 °C and monitored by TLC. After complete consumption of compound (S)-4r, the reaction mixture was quenched with saturated aqueous sodium bicarbonate. The crude mixture was extracted with EtOAc. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography on silica using a mixture of ethyl acetate and hexanes (1:5) as an eluent to provide the desired product (S)-9 as pale yellow oil in 81% yield (61 mg) and 99% ee.

■

Udmark, J.; Jørgensen, K. A. Enantioselective Formation of Substituted 3,4-Dihydrocoumarins by a Multicatalytic One-Pot Process. Org. Lett. 2012, 14, 5526−5529. (c) Stevens, J. M.; MacMillan, D. W. C. Enantioselective α-Alkenylation of Aldehydes with Boronic Acids via the Synergistic Combination of Copper(II) and Amine Catalysis. J. Am. Chem. Soc. 2013, 135, 11756−11759. (d) Quintard, A.; Constantieux, T.; Rodriguez, J. An Iron/AmineCatalyzed Cascade Process for the Enantioselective Functionalization of Allylic Alcohols. Angew. Chem., Int. Ed. 2013, 52, 12883−12887. (e) Roudier, M.; Constantieux, T.; Quintard, A.; Rodriguez, J. Enantioselective Cascade Formal Reductive Insertion of Allylic Alcohols into the C(O)−C Bond of 1,3-Diketones: Ready Access to Synthetically Valuable 3-Alkylpentanol Units. Org. Lett. 2014, 16, 2802−2805. (f) Chen, J.-R.; Hu, X.-Q.; Xiao, W.-J. Metal-Containing Carbonyl Ylides: Versatile Reactants in Catalytic Enantioselective Cascade Reactions. Angew. Chem., Int. Ed. 2014, 53, 4038−4040. (g) He, G.; Wu, F.; Huang, W.; Zhou, R.; Ouyang, L.; Han, B. OnePot Asymmetric Synthesis of Substituted Tetrahydrofurans via a Multicatalytic Benzoin/Michael/Acetalization Cascade. Adv. Synth. Catal. 2014, 356, 2311−2319. (h) Quintard, A.; Rodriguez, J. Bicatalyzed Three-Component Stereoselective Decarboxylative Fluoro-Aldolization for the Construction of Elongated Fluorohydrins. ACS Catal. 2017, 7, 5513−5517. (i) Fuchs, P. J. W.; Zeitler, K. An NHeterocyclic Carbene-Mediated, Enantioselective and Multicatalytic Strategy to Access Dihydropyranones in a Sequential ThreeComponent One-Pot Reaction. Org. Lett. 2017, 19, 6076−6079. (3) For selected reviews on one-pot reactions exploiting the different modes of activation of a single catalyst, see: (a) Shindoh, N.; Takemoto, Y.; Takasu, K. Auto-Tandem Catalysis: A Single Catalyst Activating Mechanistically Distinct Reactions in a Single Reactor. Chem. - Eur. J. 2009, 15, 12168−12179. (b) Grondal, C.; Jeanty, M.; Enders, D. Organocatalytic Cascade Reactions as a New Tool in Total Synthesis. Nat. Chem. 2010, 2, 167−178. (c) Camp, J. E. AutoTandem Catalysis: Activation of Multiple, Mechanistically Distinct Process by a Single Catalyst. Eur. J. Org. Chem. 2017, 18, 425−433. (4) For selected examples of asymmetric one-pot reactions using the different modes of activation of a single catalyst, see: (a) Enders, D.; Hü ttl, M. R. M.; Grondal, C.; Raabe, G. Control of Four Stereocentres in a Triple Cascade Organocatalytic Reaction. Nature 2006, 441, 861−863. (b) Kanbayashi, N.; Takenaka, K.; Okamura, T.; Onitsuka, K. Asymmetric Auto-Tandem Catalysis with a Planar-Chiral Ruthenium Complex: Sequential Allylic Amidation and AtomTransfer Radical Cyclization. Angew. Chem., Int. Ed. 2013, 52, 4897−4901. (c) Trost, B. M.; Ryan, M. C.; Rao, M.; Markovic, T. Z. Construction of Enantioenriched [3.1.0] Bicycles via a RutheniumCatalyzed Asymmetric Redox Bicycloisomerization Reaction. J. Am. Chem. Soc. 2014, 136, 17422−17425. (d) Liu, Y.; Xie, Y.; Wang, H.; Huang, H. Enantioselective Aminomethylamination of Conjugated Dienes with Aminals Enabled by Chiral Palladium ComplexCatalyzed C−N Bond Activation. J. Am. Chem. Soc. 2016, 138, 4314−4317. (5) (a) Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Enantioselective Mannich-Type Reaction Catalyzed by a Chiral Brønsted Acid. Angew. Chem., Int. Ed. 2004, 43, 1566−1568. (b) Uraguchi, D.; Terada, M. Chiral Brønsted Acid-Catalyzed Direct Mannich Reactions via Electrophilic Activation. J. Am. Chem. Soc. 2004, 126, 5356−5357. (6) For reviews on chiral phosphoric acid catalysis, see: (a) Akiyama, T. Stronger Brønsted Acids. Chem. Rev. 2007, 107, 5744−5758. (b) Terada, M. Binaphthol-Derived Phosphoric Acid as a Versatile Catalyst for Enantioselective Carbon−Carbon Bond Forming Reactions. Chem. Commun. 2008, 4097−4112. (c) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates. Chem. Rev. 2014, 114, 9047−9153. (d) Akiyama, T.; Mori, K. Stronger Brønsted Acids: Recent Progress. Chem. Rev. 2015, 115, 9277−9306.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b01709. Copies of 1H and 13C NMR spectra for all compounds, HPLC traces of 4, 8, and 9 (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*Phone: +82-2-3290-3147. Fax: +82-2-3290-3121. E-mail: [email protected]. ORCID

Cheol-Hong Cheon: 0000-0002-6738-6193 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean Government (NRF-2015R1D1A1A01057200 and NRF-20100020209). C.H.C. thanks the financial support from an NRF grant funded by the Korean Government (NRF-2014-011165, Center for New Directions in Organic Synthesis).

■

REFERENCES

(1) For selected reviews on multicatalytic one-pot reactions, see: (a) Zhao, Z.; Zhang, H. Combining Transition Metal Catalysis and Organocatalysis: A Broad New Concept for Catalysis. Chem. Soc. Rev. 2009, 38, 2745−2755. (b) Zhou, J. Recent Advances in Multicatalyst Promoted Asymmetric Tandem Reactions. Chem. - Asian J. 2010, 5, 422−434. (c) Rueping, M.; Koenigs, R. M.; Atodiresei, I. Unifying Metal and Brønsted Acid CatalysisConcepts, Mechanisms, and Classifications. Chem. - Eur. J. 2010, 16, 9350−9365. (d) Tian, L.; Luo, Y.-C.; Hu, X.-Q.; Xu, P.-F. Recent Developments in the Synthesis of Chiral Compounds with Quaternary Centers by Organocatalytic Cascade Reactions. Asian J. Org. Chem. 2016, 5, 580−607. (2) For recent examples of asymmetric multicatalytic one-pot reactions, see: (a) Liu, Y.; Nappi, M.; Escucero-Adán, E. C.; Melchiorre, P. Multicatalytic Asymmetric Synthesis of Complex Tetrahydrocarbazoles via a Diels-Alder/Benzoin Reaction Sequence. Org. Lett. 2012, 14, 1310−1313. (b) Jacobsen, C. B.; Albrecht, Ł.; 12493

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry (7) For selected examples of multicatalytic cascade reaction using chiral phosphoric acid catalyst, see: (a) Mukherjee, S.; List, B. Chiral Counteranions in Asymmetric Transition-Metal Catalysis: Highly Enantioselective Pd/Brønsted Acid-Catalyzed Direct α-Allylation of Aldehydes. J. Am. Chem. Soc. 2007, 129, 11336−11337. (b) Wang, C.; Han, Z. Y.; Luo, H. W.; Gong, L. Z. Highly Enantioselective Relay Catalysis in the Three-Component Reaction for Direct Construction of Structurally Complex Heterocycles. Org. Lett. 2010, 12, 2266− 2269. (c) Han, Z. Y.; Chen, D. F.; Wang, Y. Y.; Guo, R.; Wang, P. S.; Wang, C.; Gong, L. Z. Hybrid Metal/Organo Relay Catalysis Enables Enynes to be Latent Dienes for Asymmetric Diels-Alder Reaction. J. Am. Chem. Soc. 2012, 134, 6532−6535. (d) Gregory, A. W.; Jakubec, P.; Turner, P.; Dixon, D. J. Gold and BINOL-Phosphoric Acid Catalyzed Enantioselective Hydroamination/N-Sulfonyliminium Cyclization Cascade. Org. Lett. 2013, 15, 4330−4333. (e) He, Y.-P.; Wu, H.; Chen, D.-F.; Yu, J.; Gong, L.-Z. Cascade Hydroamination/Redox Reaction for the Synthesis of Cyclic Aminals Catalyzed by a Combined Gold Complex and Brønsted Acid. Chem. - Eur. J. 2013, 19, 5232−5237. (f) Zhao, F.; Li, N.; Zhu, Y.-F.; Han, Z.-Y. Enantioselective Construction of Functionalized Tetrahydrocarbazoles Enabled by Asymmetric Relay Catalysis of Gold Complex and Chiral Brønsted Acid. Org. Lett. 2016, 18, 1506−1509. (8) For selected reviews of tetrahydroquinoline, see: (a) Zhou, Y. Asymmetric Hydrogenation of Heteroaromatic Compounds. Acc. Chem. Res. 2007, 40, 1357−1366. (b) Sridharan, V.; Suryavanshi, P. A.; Menéndez, J. C. Advances in the Chemistry of Tetrahydroquinolines. Chem. Rev. 2011, 111, 7157−7259. (9) For selected examples of the enantioselective synthesis of tetrahydroquinolines via metal-catalyzed asymmetric hydrogenation of quinolines, see: (a) Wang, W.; Lu, S.; Yang, P.; Han, X.; Zhou, Y. Highly Enantioselective Iridium-Catalyzed Hydrogenation of Heteroaromatic Compounds, Quinolines. J. Am. Chem. Soc. 2003, 125, 10536−10537. (b) Lu, S.; Wang, Y.; Han, X.; Zhou, Y. Asymmetric Hydrogenation of Quinolines andIsoquinolines Activated by Chloroformates. Angew. Chem., Int. Ed. 2006, 45, 2260−2263. (c) Tang, W.; Zhu, S.; Xu, L.; Zhuo, Q.; Fan, Q.; Zhuo, H.; Lam, K.; Chan, A. S. C. Asymmetric Hydrogenation of Quinolines with High Substrate/ Catalyst Ratio. Chem. Commun. 2007, 613−615. (d) Rueping, M.; Koenigs, R. M. Brønsted Acid Differentiated Metal Catalysis by Kinetic Discrimination. Chem. Commun. 2011, 47, 304−306. (e) Wang, T.; Zhuo, L. G.; Li, Z.; Chen, F.; Fan, Q. H.; Xiang, J.; Yu, Z.-X.; Chan, A. S. C. Highly Enantioselective Hydrogenation of Quinolines Using Phosphine-Free Chiral Cationic Ruthenium Catalysts: Scope, Mechanism, and Origin of Enantioselectivity. J. Am. Chem. Soc. 2011, 133, 9878−9891. (f) Zhang, X.; Hu, Y.; Chen, C.; Fang, Q.; Wu, J.; Li, S.; Fang, W. A Supramolecularly Tunable Chiral Diphosphine Ligand: Application to Rh and Ir-Catalyzed Enantioselective Hydrogenation. Chem. Sci. 2016, 7, 4594−4599. (10) For selected examples of the enantioselective synthesis of tetrahydroquinolines via asymmetric transfer hydrogenation of quinolines, see: (a) Rueping, M.; Antonchick, A. P.; Theissmann, T. A Highly Enantioselective Brønsted Acid Catalyzed Cascade Reaction: Organocatalytic Transfer Hydrogenation of Quinolines and their Application in the Synthesis of Alkaloids. Angew. Chem., Int. Ed. 2006, 45, 3683−3686. (b) Guo, Q.; Du, D.; Xu, J. The Development of Double Axially Chiral Phosphoric Acids and Their Catalytic Transfer Hydrogenation of Quinolines. Angew. Chem., Int. Ed. 2008, 47, 759−762. (c) Rueping, M.; Stoeckel, M.; Sugiono, E.; Theissmann, T. Asymmetric Metal-Free Synthesis of Fluoroquinolones by Organocatalytic Hydrogenation. Tetrahedron 2010, 66, 6565−6568. (d) Rueping, M.; Theissmann, T.; Stoeckel, M.; Antonchick, A. P. Direct Enantioselective Access to 4-Substituted Tetrahydroquinolines by Catalytic Asymmetric Transfer Hydrogenation of Quinolones. Org. Biomol. Chem. 2011, 9, 6844−6850. (e) More, G. V.; Bhanage, B. M. Chiral Phosphoric Acid Catalyzed Asymmetric Transfer Hydrogenation of Quinolines in a Sustainable Solvent. Tetrahedron: Asymmetry 2015, 26, 1174−1179. (11) For selected examples of the synthesis of optically active tetrahydroquinoline via multicatalytic one-pot reactions, see: (a) Han,

Z.-Y.; Xiao, H.; Chen, X.-H.; Gong, L.-Z. Consecutive Intramolecular Hydroamination/Asymmetric Transfer Hydrogenation under Relay Catalysis of an Achiral Gold Complex/Chiral Brønsted Acid Binary System. J. Am. Chem. Soc. 2009, 131, 9182−9183. (b) Ren, L.; Lei, T.; Ye, J.-X; Gong, L.-Z. Step-Economical Synthesis of Tetrahydroquinolines by Asymmetric Relay Catalytic Friedländer Condensation/ Transfer Hydrogenation. Angew. Chem., Int. Ed. 2012, 51, 771−774. (c) Patil, N. T.; Raut, V. S.; Tella, R. B. Enantioselective Cooperative Triple Catalysis: Unique Roles of Au(I)/Amine/Chiral Brønsted Acid Catalysts in the Addition/Cycloisomerization/Transfer Hydrogenation Cascade. Chem. Commun. 2013, 49, 570−572. (d) Liao, H.-H.; Hsiao, C.-C.; Sugiono, E.; Rueping, M. Shedding Light on Brønsted Acid Catalysis − A Photocyclization−reduction Reaction for the Asymmetric Synthesis of Tetrahydroquinolines from Aminochalcones in Batch and Flow. Chem. Commun. 2013, 49, 7953−7955. (e) Lim, C. S.; Quach, T. T.; Zhao, Y. Enantioselective Synthesis of Tetrahydroquinolines by Borrowing Hydrogen Methodology: Cooperative Catalysis by an Achiral Iridacycle and a Chiral Phosphoric Acid. Angew. Chem., Int. Ed. 2017, 56, 7176−7180. (12) (a) Chen, X.; Qiu, S.; Wang, S.; Wang, H.; Zhai, H. Blue-LightPromoted Carbon-Carbon Double Bond Isomerization and Its Application in the Syntheses of Quinolines. Org. Biomol. Chem. 2017, 15, 6349−6352. (b) Horaguchi, T.; Hosokawa, N.; Tanemura, K.; Suzuki, T. Photocyclization Reactions. Part 8 [1]. Synthesis of 2Quinolone, Quinoline and Coumarin Derivatives Using Trans-Cis Isomerization by Photoreaction. J. Heterocycl. Chem. 2002, 39, 61−67. (13) (a) Okuma, K.; Seto, J.-I. Synthesis of Indoles, 3,1Benzoxazines, and Quinolines from 2-Alkenylanilides and Active Seleniums. Phosphorus, Sulfur Silicon Relat. Elem. 2010, 185, 1014− 1020. (b) Okuma, K.; Yasuda, T.; Shioji, K.; Yokomori, Y. Novel Formation of 2-Arylquinolines and 1,3-Benzoxazines from 2-(1Alkenyl)acylanilides and Active Halogens. Bull. Chem. Soc. Jpn. 2007, 80, 1824−1827. (14) (a) Chelucci, G.; Baldino, S. Synthesis of 4-Diphenylphosphanylmethyl- and 4-Phenylthiomethyl-1,4-methano-11,11-dimethyl1,2,3,4-tetrahydroacridine: New N-P and N-S Camphor-Derived Chiral Ligands for Asymmetric Catalysis. Tetrahedron: Asymmetry 2006, 17, 1529−1536. (b) Chelucci, G.; Thummel, R. P. Sterically Hindered Phenanthrolines: Synthesis of 1,7,7-Trimethyl[2.2.1]Bicycloheptano-[2,3-B]-L, 10-Phenanthroline from (+)-Camphor. Synth. Commun. 1999, 29, 1665−1669. (c) Love, B. E.; Ren, J. An Inthernational Journal for Rapid Communication of Synthetic Organic Chemistry. Synth. Commun. 1995, 25, 73−86. (15) Muchowski, J. M.; Maddox, M. L. Concerning the Mechanism of the Friedlander Quinoline Synthesis. Can. J. Chem. 2004, 82, 461− 478. (16) Rueping and co-workers reported an excellent example of the synthesis of chiral tetrahydroquinolines from 2-aminochalcones via a one-pot reaction. However, this transformation was developed on the basis of two different catalytic systems; one for the quinoline formation with photocatalytic system and the other for the enantioselective synthesis of tetrahydroquinolines via chiral phosphoric acid catalysts. For details, see ref 11d. (17) Recently, we developed a novel protocol for the synthesis of 2substituted quinolines 2 from 2-aminochalcones 1 using iodide as a nucleophilic catalyst: Lee, S. Y.; Jeon, J.; Cheon, C.-H. Synthesis of 2Substituted Quinolines from 2-Aminostyryl Ketones Using Iodide as a Catalyst. J. Org. Chem. 2018, 83, 5177−5186. (18) For the effect of acid catalysts in the formation of quinoline 2a from 2-aminochalcone 1a and detailed optimization of other reaction parameters for the formation of tetrahydroquinoline 4a, see Table S1 in Supporting Information. (19) The optical rotation ([α]D20) of 4a was found to be −28.4 (c = 1.0, CHCl3). Since this value has the same sign as that of 4a {−25.7 (c = 1.1, CHCl3)} reported in the literature, we assigned the absolute stereochemistry of 4a as (S). Other tetrahydroquinoline derivatives were also assigned as (S) by comparison of their measured optical rotation values with those reported in the literature. For reported optical rotation values, see refs 9, 10, and 11. 12494

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495

Article

The Journal of Organic Chemistry (20) For examples of the synthesis of estrogen receptor modulator, see: (a) Wallace, O. B.; Lauwers, K. S.; Jones, S. A.; Dodge, J. A. Tetrahydroquinoline-Based Selective Estrogen Receptor Modulators (SERMs). Bioorg. Med. Chem. Lett. 2003, 13, 1907−1907. (b) Tadaoka, H.; Cartigny, D.; Nagano, T.; Gosavi, T.; Ayad, T.; Genêt, J.-P.; Ohshima, T.; Ratovelomanana-Vidal, V.; Mashima, K. Unprecedented Halide Dependence on Catalytic Asymmetric Hydrogenation of 2-Aryl- and 2-Alkyl-Substituted Quinolinium Salts by Using Ir Complexes with Difluorphos and Halide Ligands. Chem. Eur. J. 2009, 15, 9990−9994. (c) Wang, Y.; Liu, Y.; Zhang, D.; Wei, H.; Shi, M.; Wang, F. Enantioselective Rhodium-Catalyzed Dearomative Arylation or Alkenylation of Quinolinium Salts. Angew. Chem., Int. Ed. 2016, 55, 3776−3780. (21) For a review on the concept of pot economy, see: Hayashi, Y. Pot economy and one-pot synthesis. Chem. Sci. 2016, 7, 866−880. (22) (a) Yang, K.; Zhou, F.; Kuang, Z.; Gao, G.; Driver, T. G.; Song, Q. Diborane-Mediated Deoxygenation of o-Nitrostyrenes To Form Indoles. Org. Lett. 2016, 18, 4088−4091. (b) Hu, Z.; Yuan, H.; Men, Y.; Liu, Q.; Zhang, J.; Xu, X. Cross-Cycloaddition of Two Different Isocyanides: Chemoselective Heterodimerization and [3 + 2]Cyclization of 1,4-Diazabutatriene. Angew. Chem., Int. Ed. 2016, 55, 7077−7080.

12495

DOI: 10.1021/acs.joc.8b01709 J. Org. Chem. 2018, 83, 12486−12495