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Copper-catalyzed asymmetric propargylic amination of propargylic acetates with amines using BICMAP
Tetrahedron: Asymmetry 24 (2013) 1520–1523
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Copper-catalyzed asymmetric propargylic amination of propargylic acetates with amines using BICMAP Takashi Mino ⇑, Hiroyuki Taguchi, Masatoshi Hashimoto, Masami Sakamoto Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 6 September 2013 Accepted 2 October 2013 Available online 5 November 2013
The copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as a chiral ligand gave the desired products 3 in good yields and with moderate to high enantioselectivities (up to 90% ee). Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Optically active propargylic amines, known as synthetic intermediates to biologically active compounds and polyfunctional amino derivatives, have attracted considerable attention from medicinal chemists.1 In 1994, Murahashi et al. described the synthesis of propargylic amines via the copper-catalyzed propargylic aminations of propargylic esters.2 There have been only a few reports of an asymmetric version of this reaction with propargylic acetates. A few years ago, van Maarseveen et al.1g,3 and Nishibayashi et al.4 independently developed the copper-catalyzed propargylic asymmetric amination of propargylic acetates using a pybox–CuI catalyst system and a Cl–MeO–BIPHEP–CuOTf catalyst system, respectively. Recently, Hu et al. reported on this reaction using chiral tridentate P,N,N-type ligands.5 On the other hand, we recently reported the synthesis of an atropisomeric diphosphine ligand (BICMAP)6 (Fig. 1) bearing a dihydrobenzofuran (coumaran) core. The dihedral angle of the biaryl atropisomeric backbone is greatly different from BICMAP (110.2°) between the palladium complex of BICMAP (62.5°). We also reported on the rhodium-catalyzed asymmetric 1,4-addition of aryl- and alkenylboronic acids to cyclic enones using BICMAP as a ligand.7
Herein we report the copper-catalyzed propargylic amination of propargylic acetates 1 with amines 2 using (R)-BICMAP as a chiral ligand. 2. Results and discussion 2.1. Optimization of the reaction conditions The reaction of 1-phenylpropargylic acetate 1a with N-methylaniline 2a was performed in the presence of 5 mol % of CuOTf0.5C6H6 and 10 mol % of (R)-BICMAP as a model reaction (Table 1). The reaction using 1.2 equiv of diisopropylethylamine
Table 1 Optimization of the copper-catalyzed asymmetric propargylic amination of 1-phenylpropargylic acetate 1a with N-methylaniline 2a using (R)-BICMAP
OAc +
Ph
Ph
1a
N H
Me
2a
5 mol% CuOTf·0.5C6H6 10 mol% (R)-BICMAP 1.2 equiv base MeOH (0.2 M) temp., 18 hr, Ar
Ph
N
Me
Ph 3a
1.5 equiv Entry c
O
PPh2
O
PPh2
Figure 1. (R)-BICMAP ligand.
1 2 3 4d 5 6 7 a
E-mail address: [email protected] (T. Mino). 0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetasy.2013.10.007
i
Pr2NEt Pr2NEt Pr2NEt i Pr2NEt Et3N PhNMe2 PhNHMe
i i
Temp (°C)
Yielda (%)
0 0 10 10 10 10 10
59 84 68 57 66 Trace N.R.
eeb 83 83 87 79 86 — —
Isolated yield. Determined by HPLC analysis using a chiral column. The absolute configuration was assigned by the comparison of the specific rotation with the reported data.4c c This reaction was carried out using 0.1 M of MeOH as a solvent. d 5.5 mol % of (R)-BICMAP was added. b
⇑ Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
Base
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as a base in MeOH (0.1 M) at 0 °C for 18 h produced the corresponding product 3a in 59% yield with 83% ee (entry 1). When the reaction was carried out in 0.2 M of MeOH, the yield of product 3a increased to 84% with 83% ee (entry 2). Next, the effect of the reaction temperature was investigated. The reaction at 10 °C gave 3a with good enantioselectivity (87% ee) and with 68% yield (entry 3). When the reaction was carried out using 5.5 mol % of (R)-BICMAP, the enantioselectivity decreased to 79% ee with moderate yield (entry 4). We also investigated the effect of a base. In the case of using triethylamine as a base, the enantioselectivity and yield were slightly decreased (entry 5). The reaction using N,N-dimethylaniline and N-methylaniline did not result in the corresponding product 3a (entries 6 and 7). Nishibayashi et al. already reported4c that the reaction using similar axial chiral bisphosphine ligands such as SEGPHOS and Cl–MeO–BIPHEP gave the corresponding product 3a with 59% ee and 86% ee, respectively. The enantioselectivity of product 3a using BICMAP (entry 3) was better than that of SEGPHOS and a similar level of Cl–MeO–BIPHEP.
did not proceed (entry 9). Using N-ethyl-4-chloroaniline 2f led to product 3j in good yield and with high enantioselectivity (88% ee) (entry 11). The reactions with N-ethylaniline 2g and aniline 2h gave the corresponding products with 82% ee and 44% ee, respectively (entries 12 and 13). Finally, we tested the reaction of indoline 2i as an amine. The reaction produced the corresponding product 3m with 70% ee (entry 14). The absolute configurations of products 3 were assigned by comparison of the specific rotation with reported data4a,c or were tentatively assigned by analogy. Based on the model of the transition state for the asymmetric propargylic amination of propargylic acetate with BIPHEP type ligand by Nishibayashi,4c the crystal structure of the PdCl2–BICMAP complex,6and the observed absolute configuration of the major enantiomer using (R)-BICMAP, we proposed a model for the enantioinduction (Scheme 1). The attack of N-methylaniline occurs at the cationic c-carbon atom of the ligand in the copper acetylide complex. As a result, the (S)-product was obtained in this reaction using (R)-BICMAP.
2.2. Substrate scope and limitation Under the optimized reaction conditions (Table 1, entry 3), we investigated a copper-catalyzed asymmetric propargylic amination of propargylic acetate 1 with amine 2 using (R)-BICMAP (Table 2). The reactions with 1-(4-methylphenyl)propargylic acetate 1b and 1-(4-chlorophenyl)propargylic acetate 1c with N-methylaniline 2a gave the corresponding products in good enantioselectivites (entries 2 and 3). On the other hand, the reaction using 1-(4-methoxyphenyl)propargylic acetate 1d led to low enantioselectivity (37% ee) (entry 4). When we used 1-(2-methylphenyl)propargylic acetate 1e and 1-(2-naphthyl)propargylic acetate 1f, the reactions generated corresponding products with good enantioselectivities (entries 5 and 6). We also investigated the reactions of 1-phenylpropargylic acetate 1a with various N-methylaniline derivatives 2. The reactions with N-methyl-4methylaniline 2b, N-methyl-4-methoxyaniline 2c, and N-methyl4-chloroaniline 2e resulted in the corresponding products with 83% ee, 79% ee, and 90% ee, respectively (entries 7, 8 and 10). However, the reaction with N-methyl-4-trifluoromethylaniline 2d Table 2 The scope and limitations of the copper-catalyzed asymmetric propargylic amination of propargylic acetate 1 with amine 2 using (R)-BICMAP
OAc
Ar 2 +
Ar1 1
N H
R
5 mol% CuOTf·0.5C6H6 10 mol% (R)-BICMAP 1.2 equiv i Pr2NEt MeOH (0.2 M) -10 °C, 18 hr, Ar
2
Ar 2
N
a b
Entry
Ar
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Ph 1a 4-MeC6H4 1b 4-ClC6H4 1c 4-MeOC6H4 1d 2-MeC6H4 1e 2-Naphth 1f Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a
Ar2
R
Ph Ph Ph Ph Ph Ph 4-MeC6H4 4-MeOC6H4 4-CF3C6H4 4-ClC6H4 4-ClC6H4 Ph Ph Indoline 2i
Me 2a Me 2a Me 2a Me 2a Me 2a Me 2a Me 2b Me 2c Me 2d Me 2e Et 2f Et 2g H 2h
Isolated yield. Determined by HPLC analysis using a chiral column.
P O
P
Cu
Ph H Ph
Ph
N H
Me
H
N
Me
(S)
+
Scheme 1. Proposed model for the enantioinduction.
3. Conclusions In conclusion, we have found that the copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as the chiral ligand and diisopropylethylamine as the base generated the desired products 3 with good yields and with moderate to high enantioselectivities (up to 90% ee) at 10 °C in MeOH. 4. Experimental
R
4.1. General
Ar1 3
1.5 equiv 1
O
Yielda (%) 68 3a 85 3b 68 3c 85 3d 68 3e 52 3f 63 3g 80 3h N.R. 70 3i 67 3j 54 3k 83 3l 77 3m
eeb 87 77 87 37 81 72 83 79 — 90 88 82 44 70
Melting points were measured on a AS ONE micromelting point apparatus and are uncorrected. The 1H and 13C NMR spectra were recorded in CDCl3 on a Bruker DPX-300 spectrometer or JEOL ESA500 spectrometer. The chemical shifts of the 1H NMR spectra are reported relative to TMS (d 0.00) and 13C NMR spectra are reported relative to CDCl3 (d 77.0), as an internal standard. Mass spectra were determined on a Shimadzu GCMS-QP5050A using EI, and presented as m/z (% rel intensity). HRMS were recorded on a Thermo Fisher Scientific Exactive using ESI. Analytical highperfomance liquid chromatography (HPLC) was done with a JASCO GULLIVER 900 or 2000 system coupled with a UV detector using a chiral column. Optical rotations were measured on JASCO P-2100. 4.2. General procedure for the copper-catalyzed asymmetric propargylic amination of aropargylic acetate 1 with amine 2 Under an argon atmosphere, CuOTf0.5C6H6 (2.5 mg, 10 lmol) was added to (R)-BICMAP (12.7 mg, 20 lmol) in MeOH (1 mL).
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The mixture was stirred for 1 h at 60 °C and concentrated under reduced pressure. Propargylic acetate 1 (0.20 mmol) in MeOH (1 mL), amine 2 (0.30 mmol), and diisopropylethylamine (42.0 lL, 0.24 mmol) were added to the copper complex. A mixture was stirred at 10 °C under an argon atmosphere. After 18 h, the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane or hexane/ EtOAc = 250–100/1). 4.2.1. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)aniline 3a4c (Table 2, entry 1) 68% Yield (30.3 mg), 87% ee; ½a20 D ¼ þ6:2 (c 0.27, CHCl3) {lit. 1 ½a22 D ¼ þ10:7 (c 1.42, CHCl3) as 86% ee}; yellow oil; H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 2.4 Hz, 1H), 2.70 (s, 3H), 5.81 (s, 1H), 6.86 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 8.1 Hz, 2H), 7.26–7.41 (m, 5H), 7.59 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 33.6, 56.3, 74.8, 79.9, 115.2, 118.9, 127.5, 127.8, 128.4, 129.2, 137.8, 150.1; EI-MS m/z (rel intensity) 221 (M+, 24); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1,0 mL/ min) tR = 5.6 min (minor) and 7.2 min (major). 4.2.2. (S)-()-N-Methyl-N-[1-(4-methylphenyl)-2-propynyl]aniline 3b4a (Table 2, entry 2) 85% Yield (39.8 mg), 77% ee; ½a20 D ¼ 1:4 (c 0.50, CHCl3); pale yellow solid; mp 56–57 °C; 1H NMR (CDCl3, 300 MHz) d 2.36 (s, 3H), 2.51 (d, J = 2.7 Hz, 1H), 2.69 (s, 3H), 5.78 (s, 1H), 6.85 (t, J = 7.3 Hz, 1H), 6.99 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.25–7.32 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 21.1, 33.5, 56.0, 74.6, 80.1, 115.2, 118.8, 127.4, 129.1, 129.1, 134.8, 137.5, 150.1; EI-MS m/z (rel intensity) 235 (M+, 19); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.6 min (minor) and 7.8 min (major). 4.2.3. (S)-()-N-Methyl-N-[1-(4-chlorophenyl)-2-propynyl]aniline 3c4a (Table 2, entry 3) 68% Yield (34.8 mg), 87% ee; ½a20 D ¼ 12:1 (c 0.49, CHCl3); pale yellow solid; mp 70–71 °C; 1H NMR (CDCl3, 300 MHz) d 2.54 (d, J = 2.3 Hz, 1H), 2.68 (s, 3H), 5.74 (s, 1H), 6.87 (t, J = 7.3 Hz, 1H), 6.98 (d, J = 8.2 Hz, 2H), 7.25–7.36 (m, 4H), 7.52 (d, J = 8.5 Hz, 2H); 13 C NMR (CDCl3, 75 MHz) d 33.7, 56.0, 75.2, 79.4, 115.5, 119.2, 128.6, 128.9, 129.2, 133.7, 136.4, 149.9; EI-MS m/z (rel intensity) 255 (M+, 24); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 6.3 min (minor) and 7.4 min (major). 4.2.4. (S)-()-N-Methyl-N-[1-(4-methoxyphenyl)-2-propynyl]aniline 3d4a (Table 2, entry 4) 85% Yield (42.7 mg), 37% ee; ½a20 D ¼ 8:0 (c 0.25, CHCl3); pale yellow solid; mp 47–48 °C; 1H NMR (CDCl3, 500 MHz) d 2.50 (d, J = 2.4 Hz, 1H), 2.68 (s, 3H), 3.82 (s, 3H), 5.75 (d, J = 2.0 Hz, 1H), 6.84–6.92 (m, 3H), 6.99 (d, J = 8.0 Hz, 2H), 7.25–7.31 (m, 2H), 7.47–7.50 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 33.4, 55.3, 55.7, 74.6, 80.2, 113.7, 115.3, 118.9, 128.7, 129.1, 129.8, 150.1, 159.2; EI-MS m/z (rel intensity) 251 (M+, 8); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 8.3 min (minor) and 10.6 min (major). 4.2.5. (S)-(+)-N-Methyl-N-[1-(2-methylphenyl)-2-propynyl]aniline 3e4c (Table 2, entry 5) 68% Yield (32.2 mg), 81% ee; ½a20 D ¼ þ41:2 (c 0.25, CHCl3) {lit. ½a25 D ¼ þ51 (c 1.41, CHCl3) as 82% ee}; pale yellow solid; mp 80– 81 °C; 1H NMR (CDCl3, 300 MHz) d 2.28 (s, 3H), 2.49 (d, J = 2.3 Hz, 1H), 2.63 (s, 3H), 5.78 (s, 1H), 6.85 (t, J = 7.2 Hz, 1H), 7.01 (d, J = 8.3 Hz, 2H), 7.17–7.20 (m, 1H), 7.24–7.34 (m, 4H), 7.78–7.81 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 19.1, 33.0, 53.7, 74.7, 80.1,
114.8, 118.7, 125.7, 128.1, 128.8, 129.2, 130.7, 135.4, 137.3, 149.8; EI-MS m/z (rel intensity) 235 (M+, 23); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.0 min (minor) and 5.5 min (major). 4.2.6. (S)-()-N-Methyl-N-[1-(naphthalen-2-yl)-2-propynyl]aniline 3f4a (Table 2, entry 6) 51% Yield (27.6 mg), 72% ee; ½a20 D ¼ 7:1 (c 0.81, CHCl3); pale yellow solid; mp 78–79 °C; 1H NMR (CDCl3, 300 MHz) d 2.56 (d, J = 2.3 Hz, 1H), 2.63 (s, 3H), 6.36 (s, 1H), 6.90 (t, J = 7.3 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 7.34–7.53 (m, 5H), 7.84–7.94 (m, 3H), 8.04 (d, J = 7.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 33.1, 53.3, 75.1, 80.0, 114.7, 118.7, 123.6, 125.0, 125.9, 126.6, 127.0, 128.7, 129.2, 129.3, 131.2, 132.7, 133.9, 149.4; EI-MS m/z (rel intensity) 271 (M+, 19); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.6 min (minor) and 7.8 min (major). 4.2.7. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-methylaniline 3g4a (Table 2, entry 7) 63% Yield (29.5 mg), 83% ee; ½a20 D ¼ þ16:8 (c 0.25, CHCl3); pale yellow oil; 1H NMR (CDCl3, 300 MHz) d 2.29 (s, 3H), 2.51 (d, J = 2.3 Hz, 1H), 2.65 (s, 3H), 5.73 (s, 1H), 6.92 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H), 7.31–7.39 (m, 3H), 7.59 (d, J = 7.5 Hz, 2H); 13 C NMR (CDCl3, 75 MHz) d 20.4, 33.7, 57.0, 74.9, 79.8, 115.9, 127.6, 127.7, 128.4, 128.5, 129.7, 137.9, 148.0; EI-MS m/z (rel intensity) 235 (M+, 48); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.1 min (minor) and 6.7 min (major). 4.2.8. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-methoxyaniline 3h4c (Table 2, entry 8) 80% Yield (40.2 mg), 79% ee; ½a20 D ¼ þ12:7 (c 0.52, CHCl3) {lit. 1 ½a25 D ¼ þ13 (c 1.38, CHCl3) as 80% ee}; brown oil; H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 1.8 Hz, 1H), 2.61 (s, 3H), 3.78 (s, 3H), 5.59 (s, 1H), 6.87 (d, J = 9.1 Hz, 2H), 7.00 (d, J = 9.1 Hz, 2H), 7.31–7.40 (m, 3H), 7.61 (d, J = 7.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 34.2, 55.6, 58.6, 75.3, 79.7, 114.4, 118.5, 127.7, 127.8, 128.3, 128.7, 137.9, 144.6, 153.6; EI-MS m/z (rel intensity) 251 (M+, 21); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/ 2-propanol = 97:3, 1.0 mL/min) tR = 7.3 min (minor) and 17.8 min (major). 4.2.9. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-chloroaniline 3i4a (Table 2, entry 10) 70% Yield (36.8 mg), 90% ee; ½a20 D ¼ þ3:3 (c 0.28, CHCl3); pale yellow oil; 1H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 2.3 Hz, 1H), 2.68 (s, 3H), 5.72 (s, 1H), 6.89 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 8.9 Hz, 2H), 7.32–7.40 (m, 3H), 7.54–7.56 (d, J = 7.3 Hz, 2H); 13 C NMR (CDCl3, 75 MHz) d 33.9, 56.6, 75.0, 79.5, 116.5, 123.8, 127.4, 127.9, 128.5, 129.0, 137.3, 148.6; EI-MS m/z (rel intensity) 255 (M+, 17); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 6.3 min (minor) and 8.2 min (major). 4.2.10. (S)-()-N-Ethyl-N-(1-phenyl-2-propynyl)-p-chloroaniline 3j (Table 2, entry 11) 67% Yield (36.2 mg), 88% ee; ½a20 D ¼ 27:1 (c 0.22, CHCl3); yellow oil; 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.0 Hz, 3H), 2.53 (d, J = 2.4 Hz, 1H), 3.22–3.34 (m, 2H), 5.61 (s, 1H), 6.84 (d, J = 8.9 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 7.30–7.39 (m, 3H), 7.55 (d, J = 7.3 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.2, 42.8, 56.2, 74.7, 80.8, 117.2, 123.5, 127.4, 127.8, 128.5, 128.8, 137.7, 146.5; EI-MS m/z (rel intensity) 269 (M+, 14); HRMS (ESI-orbitrap) m/z calcd for C17H16NCl+H 270.1038, found: 270.1044; HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm,
T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.5 min (minor) and 6.0 min (major). 4.2.11. (S)-()-N-Ethyl-N-(1-phenyl-2-propynyl)aniline 3k4a (Table 2, entry 12) 54% Yield (25.2 mg), 82% ee; ½a20 D ¼ 13:8 (c 0.31, CHCl3); yellow oil; 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.1 Hz, 3H), 2.52 (d, J = 2.3 Hz, 1H), 3.24–3.35 (m, 2H), 5.69 (s, 1H), 6.82 (t, J = 7.3 Hz, 1H), 6.94 (d, J = 8.1 Hz, 2H), 7.23–7.38 (m, 5H), 7.59 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.4, 42.3, 56.0, 74.4, 81.1, 115.8, 118.5, 127.5, 127.7, 128.4, 129.0, 138.2, 148.0; EI-MS m/z (rel intensity) 235 (M+, 29); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/ min) tR = 4.5 min (minor) and 4.9 min (major). 4.2.12. (S)-(+)-N-(1-phenyl-2-propynyl)aniline 3l3 (Table 2, entry 13) 83% Yield (34.4 mg), 44% ee; ½a20 D ¼ þ33:3 (c 0.27, CHCl3) {lit. ½a20 ¼ þ103 (c 1.0, CHCl ) as 87% ee}; pale yellow solid; mp 3 D 84–85 °C; 1H NMR (CDCl3, 300 MHz) d 2.48 (d, J = 2.3 Hz, 1H), 4.05 (d, J = 6.4 Hz, 1H), 5.29 (d, J = 5.1 Hz, 1H), 6.73–6.82 (m, 3H), 7.19–7.25 (m, 2H), 7.31–7.43 (m, 3H), 7.61 (t, J = 6.9 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 49.8, 73.1, 83.0, 114.0, 118.8, 127.2, 128.2, 128.8, 129.2, 139.0, 146.3; EI-MS m/z (rel intensity) 207 (M+, 30); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 98:2, 1.0 mL/min) tR = 26.7 min (major) and 34.8 min (minor). 4.2.13. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)indoline 3m4a (Table 2, entry 14) 77% Yield (36.1 mg), 70% ee; ½a20 D ¼ þ54:3 (c 0.23, CHCl3); brown oil; 1H NMR (CDCl3, 300 MHz) d 2.39 (d, J = 2.2 Hz, 1H), 2.95 (t, J = 9.0 Hz, 2H), 3.08–3.15 (m, 1H), 3.29–3.38 (m, 2H), 5.61 (s, 1H), 6.64 (d, J = 7.8 Hz, 1H), 6.74 (t, J = 7.5 Hz, 1H), 7.11 (t,
1523
J = 7.7 Hz, 2H), 7.32–7.41 (m, 3H), 7.66 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 28.2, 49.0, 52.8, 74.5, 79.4, 108.5, 118.9, 124.6, 127.1, 127.8, 127.9, 128.4, 130.8, 137.1, 150.6; EI-MS m/z (rel intensity) 233 (M+, 46); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.4 min (minor) and 8.4 min (major). Acknowledgments This work was supported by a Grant-in-Aid for Young Scientists (WAKATE B-22750082) from the Ministry of Education, Culture, Sports, Science and Technology, Japan and the COE Start-up Program in the Chiba University. References 1. (a) Porco, J. A., Jr.; Schoenen, F. J.; Stout, T. J.; Clardy, J.; Schreiber, S. L. J. Am. Chem. Soc. 1990, 112, 7410–7411; (b) Nicolaou, K. C.; Hwang, C.-K.; Smith, A. L.; Wendeborn, S. V. J. Am. Chem. Soc. 1990, 112, 7416–7418; (c) Yu, P. H.; Davis, B. A.; Boulton, A. A. J. Med. Chem. 1992, 35, 3705–3713; (d) Jiang, B.; Xu, M. Angew. Chem., Int. Ed. 2004, 43, 2543–2546; (e) Yamamoto, Y.; Hayashi, H.; Saigoku, T.; Nishiyama, H. J. Am. Chem. Soc. 2005, 127, 10804–10805; (f) Fleming, J. J.; Du Bois, J. J. Am. Chem. Soc. 2006, 128, 3926–3927; (g) Detz, R. J.; Abiri, Z.; le Griel, R.; Hiemstra, H.; van Maarseveen, J. H. Chem. Eur. J. 2011, 17, 5921–5930. 2. Imada, Y.; Yuasa, M.; Nakamura, S.; Murahashi, S.-I. J. Org. Chem. 1994, 59, 2282– 2284. 3. Detz, R. J.; Delville, M. M. E.; Hiemstra, H.; van Maarseveen, J. H. Angew. Chem., Int. Ed. 2008, 47, 3777–3780. 4. (a) Hattori, G.; Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed. 2008, 47, 3781–3783; (b) Matsuzawa, H.; Tanage, Y.; Miyake, Y.; Nishibayashi, Y. Organometallics 2008, 27, 4021–4024; (c) Hattori, G.; Sakata, K.; Matsuzawa, H.; Tanabe, Y.; Miyake, Y.; Nishibayashi, Y. J. Am. Chem. Soc. 2010, 132, 10592– 10608. 5. Zhang, C.; Wnag, Y.-H.; Hu, X.-H.; Zheng, Z.; Xu, J.; Hu, X.-P. Adv. Synth. Catal. 2012, 354, 2854–2858. 6. Mino, T.; Naruse, Y.; Kobayashi, S.; Oishi, S.; Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2009, 50, 2239–2241. 7. Mino, T.; Hashimoto, M.; Uehara, K.; Naruse, Y.; Kobayashi, S.; Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2012, 53, 4562.
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Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy
Copper-catalyzed asymmetric propargylic amination of propargylic acetates with amines using BICMAP Takashi Mino ⇑, Hiroyuki Taguchi, Masatoshi Hashimoto, Masami Sakamoto Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 6 September 2013 Accepted 2 October 2013 Available online 5 November 2013
The copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as a chiral ligand gave the desired products 3 in good yields and with moderate to high enantioselectivities (up to 90% ee). Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Optically active propargylic amines, known as synthetic intermediates to biologically active compounds and polyfunctional amino derivatives, have attracted considerable attention from medicinal chemists.1 In 1994, Murahashi et al. described the synthesis of propargylic amines via the copper-catalyzed propargylic aminations of propargylic esters.2 There have been only a few reports of an asymmetric version of this reaction with propargylic acetates. A few years ago, van Maarseveen et al.1g,3 and Nishibayashi et al.4 independently developed the copper-catalyzed propargylic asymmetric amination of propargylic acetates using a pybox–CuI catalyst system and a Cl–MeO–BIPHEP–CuOTf catalyst system, respectively. Recently, Hu et al. reported on this reaction using chiral tridentate P,N,N-type ligands.5 On the other hand, we recently reported the synthesis of an atropisomeric diphosphine ligand (BICMAP)6 (Fig. 1) bearing a dihydrobenzofuran (coumaran) core. The dihedral angle of the biaryl atropisomeric backbone is greatly different from BICMAP (110.2°) between the palladium complex of BICMAP (62.5°). We also reported on the rhodium-catalyzed asymmetric 1,4-addition of aryl- and alkenylboronic acids to cyclic enones using BICMAP as a ligand.7
Herein we report the copper-catalyzed propargylic amination of propargylic acetates 1 with amines 2 using (R)-BICMAP as a chiral ligand. 2. Results and discussion 2.1. Optimization of the reaction conditions The reaction of 1-phenylpropargylic acetate 1a with N-methylaniline 2a was performed in the presence of 5 mol % of CuOTf0.5C6H6 and 10 mol % of (R)-BICMAP as a model reaction (Table 1). The reaction using 1.2 equiv of diisopropylethylamine
Table 1 Optimization of the copper-catalyzed asymmetric propargylic amination of 1-phenylpropargylic acetate 1a with N-methylaniline 2a using (R)-BICMAP
OAc +
Ph
Ph
1a
N H
Me
2a
5 mol% CuOTf·0.5C6H6 10 mol% (R)-BICMAP 1.2 equiv base MeOH (0.2 M) temp., 18 hr, Ar
Ph
N
Me
Ph 3a
1.5 equiv Entry c
O
PPh2
O
PPh2
Figure 1. (R)-BICMAP ligand.
1 2 3 4d 5 6 7 a
E-mail address: [email protected] (T. Mino). 0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetasy.2013.10.007
i
Pr2NEt Pr2NEt Pr2NEt i Pr2NEt Et3N PhNMe2 PhNHMe
i i
Temp (°C)
Yielda (%)
0 0 10 10 10 10 10
59 84 68 57 66 Trace N.R.
eeb 83 83 87 79 86 — —
Isolated yield. Determined by HPLC analysis using a chiral column. The absolute configuration was assigned by the comparison of the specific rotation with the reported data.4c c This reaction was carried out using 0.1 M of MeOH as a solvent. d 5.5 mol % of (R)-BICMAP was added. b
⇑ Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
Base
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T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
as a base in MeOH (0.1 M) at 0 °C for 18 h produced the corresponding product 3a in 59% yield with 83% ee (entry 1). When the reaction was carried out in 0.2 M of MeOH, the yield of product 3a increased to 84% with 83% ee (entry 2). Next, the effect of the reaction temperature was investigated. The reaction at 10 °C gave 3a with good enantioselectivity (87% ee) and with 68% yield (entry 3). When the reaction was carried out using 5.5 mol % of (R)-BICMAP, the enantioselectivity decreased to 79% ee with moderate yield (entry 4). We also investigated the effect of a base. In the case of using triethylamine as a base, the enantioselectivity and yield were slightly decreased (entry 5). The reaction using N,N-dimethylaniline and N-methylaniline did not result in the corresponding product 3a (entries 6 and 7). Nishibayashi et al. already reported4c that the reaction using similar axial chiral bisphosphine ligands such as SEGPHOS and Cl–MeO–BIPHEP gave the corresponding product 3a with 59% ee and 86% ee, respectively. The enantioselectivity of product 3a using BICMAP (entry 3) was better than that of SEGPHOS and a similar level of Cl–MeO–BIPHEP.
did not proceed (entry 9). Using N-ethyl-4-chloroaniline 2f led to product 3j in good yield and with high enantioselectivity (88% ee) (entry 11). The reactions with N-ethylaniline 2g and aniline 2h gave the corresponding products with 82% ee and 44% ee, respectively (entries 12 and 13). Finally, we tested the reaction of indoline 2i as an amine. The reaction produced the corresponding product 3m with 70% ee (entry 14). The absolute configurations of products 3 were assigned by comparison of the specific rotation with reported data4a,c or were tentatively assigned by analogy. Based on the model of the transition state for the asymmetric propargylic amination of propargylic acetate with BIPHEP type ligand by Nishibayashi,4c the crystal structure of the PdCl2–BICMAP complex,6and the observed absolute configuration of the major enantiomer using (R)-BICMAP, we proposed a model for the enantioinduction (Scheme 1). The attack of N-methylaniline occurs at the cationic c-carbon atom of the ligand in the copper acetylide complex. As a result, the (S)-product was obtained in this reaction using (R)-BICMAP.
2.2. Substrate scope and limitation Under the optimized reaction conditions (Table 1, entry 3), we investigated a copper-catalyzed asymmetric propargylic amination of propargylic acetate 1 with amine 2 using (R)-BICMAP (Table 2). The reactions with 1-(4-methylphenyl)propargylic acetate 1b and 1-(4-chlorophenyl)propargylic acetate 1c with N-methylaniline 2a gave the corresponding products in good enantioselectivites (entries 2 and 3). On the other hand, the reaction using 1-(4-methoxyphenyl)propargylic acetate 1d led to low enantioselectivity (37% ee) (entry 4). When we used 1-(2-methylphenyl)propargylic acetate 1e and 1-(2-naphthyl)propargylic acetate 1f, the reactions generated corresponding products with good enantioselectivities (entries 5 and 6). We also investigated the reactions of 1-phenylpropargylic acetate 1a with various N-methylaniline derivatives 2. The reactions with N-methyl-4methylaniline 2b, N-methyl-4-methoxyaniline 2c, and N-methyl4-chloroaniline 2e resulted in the corresponding products with 83% ee, 79% ee, and 90% ee, respectively (entries 7, 8 and 10). However, the reaction with N-methyl-4-trifluoromethylaniline 2d Table 2 The scope and limitations of the copper-catalyzed asymmetric propargylic amination of propargylic acetate 1 with amine 2 using (R)-BICMAP
OAc
Ar 2 +
Ar1 1
N H
R
5 mol% CuOTf·0.5C6H6 10 mol% (R)-BICMAP 1.2 equiv i Pr2NEt MeOH (0.2 M) -10 °C, 18 hr, Ar
2
Ar 2
N
a b
Entry
Ar
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Ph 1a 4-MeC6H4 1b 4-ClC6H4 1c 4-MeOC6H4 1d 2-MeC6H4 1e 2-Naphth 1f Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a Ph 1a
Ar2
R
Ph Ph Ph Ph Ph Ph 4-MeC6H4 4-MeOC6H4 4-CF3C6H4 4-ClC6H4 4-ClC6H4 Ph Ph Indoline 2i
Me 2a Me 2a Me 2a Me 2a Me 2a Me 2a Me 2b Me 2c Me 2d Me 2e Et 2f Et 2g H 2h
Isolated yield. Determined by HPLC analysis using a chiral column.
P O
P
Cu
Ph H Ph
Ph
N H
Me
H
N
Me
(S)
+
Scheme 1. Proposed model for the enantioinduction.
3. Conclusions In conclusion, we have found that the copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as the chiral ligand and diisopropylethylamine as the base generated the desired products 3 with good yields and with moderate to high enantioselectivities (up to 90% ee) at 10 °C in MeOH. 4. Experimental
R
4.1. General
Ar1 3
1.5 equiv 1
O
Yielda (%) 68 3a 85 3b 68 3c 85 3d 68 3e 52 3f 63 3g 80 3h N.R. 70 3i 67 3j 54 3k 83 3l 77 3m
eeb 87 77 87 37 81 72 83 79 — 90 88 82 44 70
Melting points were measured on a AS ONE micromelting point apparatus and are uncorrected. The 1H and 13C NMR spectra were recorded in CDCl3 on a Bruker DPX-300 spectrometer or JEOL ESA500 spectrometer. The chemical shifts of the 1H NMR spectra are reported relative to TMS (d 0.00) and 13C NMR spectra are reported relative to CDCl3 (d 77.0), as an internal standard. Mass spectra were determined on a Shimadzu GCMS-QP5050A using EI, and presented as m/z (% rel intensity). HRMS were recorded on a Thermo Fisher Scientific Exactive using ESI. Analytical highperfomance liquid chromatography (HPLC) was done with a JASCO GULLIVER 900 or 2000 system coupled with a UV detector using a chiral column. Optical rotations were measured on JASCO P-2100. 4.2. General procedure for the copper-catalyzed asymmetric propargylic amination of aropargylic acetate 1 with amine 2 Under an argon atmosphere, CuOTf0.5C6H6 (2.5 mg, 10 lmol) was added to (R)-BICMAP (12.7 mg, 20 lmol) in MeOH (1 mL).
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T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
The mixture was stirred for 1 h at 60 °C and concentrated under reduced pressure. Propargylic acetate 1 (0.20 mmol) in MeOH (1 mL), amine 2 (0.30 mmol), and diisopropylethylamine (42.0 lL, 0.24 mmol) were added to the copper complex. A mixture was stirred at 10 °C under an argon atmosphere. After 18 h, the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane or hexane/ EtOAc = 250–100/1). 4.2.1. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)aniline 3a4c (Table 2, entry 1) 68% Yield (30.3 mg), 87% ee; ½a20 D ¼ þ6:2 (c 0.27, CHCl3) {lit. 1 ½a22 D ¼ þ10:7 (c 1.42, CHCl3) as 86% ee}; yellow oil; H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 2.4 Hz, 1H), 2.70 (s, 3H), 5.81 (s, 1H), 6.86 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 8.1 Hz, 2H), 7.26–7.41 (m, 5H), 7.59 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 33.6, 56.3, 74.8, 79.9, 115.2, 118.9, 127.5, 127.8, 128.4, 129.2, 137.8, 150.1; EI-MS m/z (rel intensity) 221 (M+, 24); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1,0 mL/ min) tR = 5.6 min (minor) and 7.2 min (major). 4.2.2. (S)-()-N-Methyl-N-[1-(4-methylphenyl)-2-propynyl]aniline 3b4a (Table 2, entry 2) 85% Yield (39.8 mg), 77% ee; ½a20 D ¼ 1:4 (c 0.50, CHCl3); pale yellow solid; mp 56–57 °C; 1H NMR (CDCl3, 300 MHz) d 2.36 (s, 3H), 2.51 (d, J = 2.7 Hz, 1H), 2.69 (s, 3H), 5.78 (s, 1H), 6.85 (t, J = 7.3 Hz, 1H), 6.99 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.25–7.32 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 21.1, 33.5, 56.0, 74.6, 80.1, 115.2, 118.8, 127.4, 129.1, 129.1, 134.8, 137.5, 150.1; EI-MS m/z (rel intensity) 235 (M+, 19); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.6 min (minor) and 7.8 min (major). 4.2.3. (S)-()-N-Methyl-N-[1-(4-chlorophenyl)-2-propynyl]aniline 3c4a (Table 2, entry 3) 68% Yield (34.8 mg), 87% ee; ½a20 D ¼ 12:1 (c 0.49, CHCl3); pale yellow solid; mp 70–71 °C; 1H NMR (CDCl3, 300 MHz) d 2.54 (d, J = 2.3 Hz, 1H), 2.68 (s, 3H), 5.74 (s, 1H), 6.87 (t, J = 7.3 Hz, 1H), 6.98 (d, J = 8.2 Hz, 2H), 7.25–7.36 (m, 4H), 7.52 (d, J = 8.5 Hz, 2H); 13 C NMR (CDCl3, 75 MHz) d 33.7, 56.0, 75.2, 79.4, 115.5, 119.2, 128.6, 128.9, 129.2, 133.7, 136.4, 149.9; EI-MS m/z (rel intensity) 255 (M+, 24); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 6.3 min (minor) and 7.4 min (major). 4.2.4. (S)-()-N-Methyl-N-[1-(4-methoxyphenyl)-2-propynyl]aniline 3d4a (Table 2, entry 4) 85% Yield (42.7 mg), 37% ee; ½a20 D ¼ 8:0 (c 0.25, CHCl3); pale yellow solid; mp 47–48 °C; 1H NMR (CDCl3, 500 MHz) d 2.50 (d, J = 2.4 Hz, 1H), 2.68 (s, 3H), 3.82 (s, 3H), 5.75 (d, J = 2.0 Hz, 1H), 6.84–6.92 (m, 3H), 6.99 (d, J = 8.0 Hz, 2H), 7.25–7.31 (m, 2H), 7.47–7.50 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 33.4, 55.3, 55.7, 74.6, 80.2, 113.7, 115.3, 118.9, 128.7, 129.1, 129.8, 150.1, 159.2; EI-MS m/z (rel intensity) 251 (M+, 8); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 8.3 min (minor) and 10.6 min (major). 4.2.5. (S)-(+)-N-Methyl-N-[1-(2-methylphenyl)-2-propynyl]aniline 3e4c (Table 2, entry 5) 68% Yield (32.2 mg), 81% ee; ½a20 D ¼ þ41:2 (c 0.25, CHCl3) {lit. ½a25 D ¼ þ51 (c 1.41, CHCl3) as 82% ee}; pale yellow solid; mp 80– 81 °C; 1H NMR (CDCl3, 300 MHz) d 2.28 (s, 3H), 2.49 (d, J = 2.3 Hz, 1H), 2.63 (s, 3H), 5.78 (s, 1H), 6.85 (t, J = 7.2 Hz, 1H), 7.01 (d, J = 8.3 Hz, 2H), 7.17–7.20 (m, 1H), 7.24–7.34 (m, 4H), 7.78–7.81 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 19.1, 33.0, 53.7, 74.7, 80.1,
114.8, 118.7, 125.7, 128.1, 128.8, 129.2, 130.7, 135.4, 137.3, 149.8; EI-MS m/z (rel intensity) 235 (M+, 23); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.0 min (minor) and 5.5 min (major). 4.2.6. (S)-()-N-Methyl-N-[1-(naphthalen-2-yl)-2-propynyl]aniline 3f4a (Table 2, entry 6) 51% Yield (27.6 mg), 72% ee; ½a20 D ¼ 7:1 (c 0.81, CHCl3); pale yellow solid; mp 78–79 °C; 1H NMR (CDCl3, 300 MHz) d 2.56 (d, J = 2.3 Hz, 1H), 2.63 (s, 3H), 6.36 (s, 1H), 6.90 (t, J = 7.3 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 7.34–7.53 (m, 5H), 7.84–7.94 (m, 3H), 8.04 (d, J = 7.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 33.1, 53.3, 75.1, 80.0, 114.7, 118.7, 123.6, 125.0, 125.9, 126.6, 127.0, 128.7, 129.2, 129.3, 131.2, 132.7, 133.9, 149.4; EI-MS m/z (rel intensity) 271 (M+, 19); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.6 min (minor) and 7.8 min (major). 4.2.7. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-methylaniline 3g4a (Table 2, entry 7) 63% Yield (29.5 mg), 83% ee; ½a20 D ¼ þ16:8 (c 0.25, CHCl3); pale yellow oil; 1H NMR (CDCl3, 300 MHz) d 2.29 (s, 3H), 2.51 (d, J = 2.3 Hz, 1H), 2.65 (s, 3H), 5.73 (s, 1H), 6.92 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H), 7.31–7.39 (m, 3H), 7.59 (d, J = 7.5 Hz, 2H); 13 C NMR (CDCl3, 75 MHz) d 20.4, 33.7, 57.0, 74.9, 79.8, 115.9, 127.6, 127.7, 128.4, 128.5, 129.7, 137.9, 148.0; EI-MS m/z (rel intensity) 235 (M+, 48); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.1 min (minor) and 6.7 min (major). 4.2.8. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-methoxyaniline 3h4c (Table 2, entry 8) 80% Yield (40.2 mg), 79% ee; ½a20 D ¼ þ12:7 (c 0.52, CHCl3) {lit. 1 ½a25 D ¼ þ13 (c 1.38, CHCl3) as 80% ee}; brown oil; H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 1.8 Hz, 1H), 2.61 (s, 3H), 3.78 (s, 3H), 5.59 (s, 1H), 6.87 (d, J = 9.1 Hz, 2H), 7.00 (d, J = 9.1 Hz, 2H), 7.31–7.40 (m, 3H), 7.61 (d, J = 7.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 34.2, 55.6, 58.6, 75.3, 79.7, 114.4, 118.5, 127.7, 127.8, 128.3, 128.7, 137.9, 144.6, 153.6; EI-MS m/z (rel intensity) 251 (M+, 21); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/ 2-propanol = 97:3, 1.0 mL/min) tR = 7.3 min (minor) and 17.8 min (major). 4.2.9. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-chloroaniline 3i4a (Table 2, entry 10) 70% Yield (36.8 mg), 90% ee; ½a20 D ¼ þ3:3 (c 0.28, CHCl3); pale yellow oil; 1H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 2.3 Hz, 1H), 2.68 (s, 3H), 5.72 (s, 1H), 6.89 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 8.9 Hz, 2H), 7.32–7.40 (m, 3H), 7.54–7.56 (d, J = 7.3 Hz, 2H); 13 C NMR (CDCl3, 75 MHz) d 33.9, 56.6, 75.0, 79.5, 116.5, 123.8, 127.4, 127.9, 128.5, 129.0, 137.3, 148.6; EI-MS m/z (rel intensity) 255 (M+, 17); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 6.3 min (minor) and 8.2 min (major). 4.2.10. (S)-()-N-Ethyl-N-(1-phenyl-2-propynyl)-p-chloroaniline 3j (Table 2, entry 11) 67% Yield (36.2 mg), 88% ee; ½a20 D ¼ 27:1 (c 0.22, CHCl3); yellow oil; 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.0 Hz, 3H), 2.53 (d, J = 2.4 Hz, 1H), 3.22–3.34 (m, 2H), 5.61 (s, 1H), 6.84 (d, J = 8.9 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 7.30–7.39 (m, 3H), 7.55 (d, J = 7.3 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.2, 42.8, 56.2, 74.7, 80.8, 117.2, 123.5, 127.4, 127.8, 128.5, 128.8, 137.7, 146.5; EI-MS m/z (rel intensity) 269 (M+, 14); HRMS (ESI-orbitrap) m/z calcd for C17H16NCl+H 270.1038, found: 270.1044; HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm,
T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.5 min (minor) and 6.0 min (major). 4.2.11. (S)-()-N-Ethyl-N-(1-phenyl-2-propynyl)aniline 3k4a (Table 2, entry 12) 54% Yield (25.2 mg), 82% ee; ½a20 D ¼ 13:8 (c 0.31, CHCl3); yellow oil; 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.1 Hz, 3H), 2.52 (d, J = 2.3 Hz, 1H), 3.24–3.35 (m, 2H), 5.69 (s, 1H), 6.82 (t, J = 7.3 Hz, 1H), 6.94 (d, J = 8.1 Hz, 2H), 7.23–7.38 (m, 5H), 7.59 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.4, 42.3, 56.0, 74.4, 81.1, 115.8, 118.5, 127.5, 127.7, 128.4, 129.0, 138.2, 148.0; EI-MS m/z (rel intensity) 235 (M+, 29); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/ min) tR = 4.5 min (minor) and 4.9 min (major). 4.2.12. (S)-(+)-N-(1-phenyl-2-propynyl)aniline 3l3 (Table 2, entry 13) 83% Yield (34.4 mg), 44% ee; ½a20 D ¼ þ33:3 (c 0.27, CHCl3) {lit. ½a20 ¼ þ103 (c 1.0, CHCl ) as 87% ee}; pale yellow solid; mp 3 D 84–85 °C; 1H NMR (CDCl3, 300 MHz) d 2.48 (d, J = 2.3 Hz, 1H), 4.05 (d, J = 6.4 Hz, 1H), 5.29 (d, J = 5.1 Hz, 1H), 6.73–6.82 (m, 3H), 7.19–7.25 (m, 2H), 7.31–7.43 (m, 3H), 7.61 (t, J = 6.9 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 49.8, 73.1, 83.0, 114.0, 118.8, 127.2, 128.2, 128.8, 129.2, 139.0, 146.3; EI-MS m/z (rel intensity) 207 (M+, 30); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 98:2, 1.0 mL/min) tR = 26.7 min (major) and 34.8 min (minor). 4.2.13. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)indoline 3m4a (Table 2, entry 14) 77% Yield (36.1 mg), 70% ee; ½a20 D ¼ þ54:3 (c 0.23, CHCl3); brown oil; 1H NMR (CDCl3, 300 MHz) d 2.39 (d, J = 2.2 Hz, 1H), 2.95 (t, J = 9.0 Hz, 2H), 3.08–3.15 (m, 1H), 3.29–3.38 (m, 2H), 5.61 (s, 1H), 6.64 (d, J = 7.8 Hz, 1H), 6.74 (t, J = 7.5 Hz, 1H), 7.11 (t,
1523
J = 7.7 Hz, 2H), 7.32–7.41 (m, 3H), 7.66 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 28.2, 49.0, 52.8, 74.5, 79.4, 108.5, 118.9, 124.6, 127.1, 127.8, 127.9, 128.4, 130.8, 137.1, 150.6; EI-MS m/z (rel intensity) 233 (M+, 46); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.4 min (minor) and 8.4 min (major). Acknowledgments This work was supported by a Grant-in-Aid for Young Scientists (WAKATE B-22750082) from the Ministry of Education, Culture, Sports, Science and Technology, Japan and the COE Start-up Program in the Chiba University. References 1. (a) Porco, J. A., Jr.; Schoenen, F. J.; Stout, T. J.; Clardy, J.; Schreiber, S. L. J. Am. Chem. Soc. 1990, 112, 7410–7411; (b) Nicolaou, K. C.; Hwang, C.-K.; Smith, A. L.; Wendeborn, S. V. J. Am. Chem. Soc. 1990, 112, 7416–7418; (c) Yu, P. H.; Davis, B. A.; Boulton, A. A. J. Med. Chem. 1992, 35, 3705–3713; (d) Jiang, B.; Xu, M. Angew. Chem., Int. Ed. 2004, 43, 2543–2546; (e) Yamamoto, Y.; Hayashi, H.; Saigoku, T.; Nishiyama, H. J. Am. Chem. Soc. 2005, 127, 10804–10805; (f) Fleming, J. J.; Du Bois, J. J. Am. Chem. Soc. 2006, 128, 3926–3927; (g) Detz, R. J.; Abiri, Z.; le Griel, R.; Hiemstra, H.; van Maarseveen, J. H. Chem. Eur. J. 2011, 17, 5921–5930. 2. Imada, Y.; Yuasa, M.; Nakamura, S.; Murahashi, S.-I. J. Org. Chem. 1994, 59, 2282– 2284. 3. Detz, R. J.; Delville, M. M. E.; Hiemstra, H.; van Maarseveen, J. H. Angew. Chem., Int. Ed. 2008, 47, 3777–3780. 4. (a) Hattori, G.; Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed. 2008, 47, 3781–3783; (b) Matsuzawa, H.; Tanage, Y.; Miyake, Y.; Nishibayashi, Y. Organometallics 2008, 27, 4021–4024; (c) Hattori, G.; Sakata, K.; Matsuzawa, H.; Tanabe, Y.; Miyake, Y.; Nishibayashi, Y. J. Am. Chem. Soc. 2010, 132, 10592– 10608. 5. Zhang, C.; Wnag, Y.-H.; Hu, X.-H.; Zheng, Z.; Xu, J.; Hu, X.-P. Adv. Synth. Catal. 2012, 354, 2854–2858. 6. Mino, T.; Naruse, Y.; Kobayashi, S.; Oishi, S.; Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2009, 50, 2239–2241. 7. Mino, T.; Hashimoto, M.; Uehara, K.; Naruse, Y.; Kobayashi, S.; Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2012, 53, 4562.