Gold-Catalyzed Intermolecular Hydroamination of Allenes: First Example of the Use of an Aliphatic Amine in Hydroamination

Abstract

Treatment of allenes with morpholine in the presence of cationic gold(I) catalyst in toluene at 80 °C gave the corresponding allylic amines in good to moderate yields. To the best of our knowledge, this is the first example for carrying out the gold-catalyzed ­intermolecular hydroamination with an aliphatic amine.

hydroamination - gold catalyst - aliphatic amine - allenes - gold-phosphine complex

References and Notes

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4a Zhang J. Yang C.-G. He C. J. Am. Chem. Soc.  2006,  128:  1798 

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7 For an example of cationic gold(I)-catalyzed addition of nitrogen nucleophiles, see: Gorin DJ. Davis NR. Toste FD. J. Am. Chem. Soc.  2005,  127:  11260 

8

We examined the following complexes, but all attempts resulted in failure: AuCl, AuCl₃, AuBr₃, AuI, Au(CO)Cl, NaAuCl₄·2H₂O. It is known that the hydroamination of olefins with tosylamides is accelerated by TfOH, [9] so we examined the TfOH-catalyzed (10 mol%) hydroamination of 1a with 2 in toluene at 80 °C. However, the desired product (allylic amine) was not obtained at all. The allene 1a was decomposed gradually in the presence of TfOH at 80 °C, and only 30% of 1a was recovered after 12 h. It is clear that the present hydroamination is catalyzed by the gold complexes.

9a Wabnitz TC. Spencer JB. Org. Lett.  2003,  5:  2141 

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10 In order to know whether the cationic gold species really participate in the present hydroamination or not, we prepared the cationic gold species [(MeCN)AuPPh₂(o-tolyl)]^{+ -}OTf according to the Echavarren’s method and used it for the hydroamination of 1a. The product 3a was obtained in 71% yield, indicating that the cationic gold complex was a catalytic species. See: Nieto-Oberhuber C. López S. Muñoz MP. Cárdenas DJ. Buñuel E. Nevado C. Echavarren AM. Angew. Chem. Int. Ed.  2005,  44:  6146 

11 It is reported that manipulation of phosphine ligands enhances the chemical yield in Pd-catalyzed amination of aryl halides. See: Chen G. Lam WH. Fok WS. Lee HW. Kwong FY. Chem. Asian J.  2007,  2:  306 

12 Alcock NW. Moore P. Lampe PA. Mok KF. J. Chem. Soc., Dalton Trans.  1982,  207 

13

This reaction could not be checked by TLC nor GC-MS, because of its low boiling point (ca. 80 °C). Thus, reactions were stopped at 24 h.

14 General Procedure for Preparation of Catalysts These complexes were prepared following a literature procedure, and characterized by comparison of the NMR data with literature values, except for 4c, 4d, and 4h. A solution of SMe₂ (1.2 mL, 16 mmol) in MeOH (6 mL) was added to a solution of NaAuCl₄·2H₂O (2.19 g, 5.5 mmol) in MeOH (30 mL) with minimum light exposure. The white precipitate was recovered by filtration, washed (MeOH, Et₂O, and pentane), and dried under vacuum. Then, [AuCl(SMe₂)] was obtained in 99% yield (1.60 g) and used without further purification. ¹H NMR (300 MHz, CDCl₃): δ = 2.73 (s, 6 H). A solution of diphenyl(o-tolyl)phosphine (0.589 g, 2 mmol) in acetone (50 mL) was added to a solution of [AuCl(SMe₂)] (0.553 g) in acetone (150 mL). The mixture was stirred for 2 h and concentrated, recrystallized from toluene, and dried under vacuum; [AuClPPh₂(o-Me-C₆H₄)](4h) was obtained in 83% (0.83 g). See: Brandys M.-C. Jennings MC. Puddephatt RJ. J. Chem. Soc., Dalton Trans.  2000,  4601 

15

ClAuPPh₂(o-MeOC₆H₄)(4c): ¹H NMR (600 MHz, CDCl₃): δ = 3.71 (3 H, s), 6.82 (1 H, ddd, J = 13.2, 7.8, 1.8 Hz), 6.97 (1 H, dd, J = 8.4, 5.1 Hz), 6.93-6.97 (1 H, m), 7.42-7.47 (4 H, m), 7.49-7.57 (7 H, m). ¹³C NMR (75.5 Hz, CDCl₃): δ = 55.9, 111.6 [d, J(¹³C-³¹P) = 4.1 Hz], 116.4 [d, J(¹³C-³¹P) = 57.0 Hz], 121.1 [d, J(¹³C-³¹P) = 10.8 Hz], 128.4, 128.9 [d, J(¹³C-³¹P) = 11.6 Hz], 131.5 [d, J(¹³C-³¹P) = 2.5 Hz], 133.9 [d, J(¹³C-³¹P) = 1.7 Hz], 134.0 [d, J(¹³C-³¹P) = 14.9 Hz], 134.2 [d, J(¹³C-³¹P) = 7.5 Hz], 160.7 [d, J(¹³C-³¹P) = 5.0 Hz]. ³¹P NMR (121.5 Hz, CDCl₃): δ = 25.0. IR (neat, ATR): 1584, 1572, 1473, 1459, 1435, 1278, 1247, 1101, 1011, 764, 747 cm^-1. Anal. Calcd for C₁₉H₁₇AuClOP: C, 43.49; H, 3.27; Cl, 6.76. Found: C, 43.62; H, 3.32; Cl, 6.75. ESI-HRMS: m/z calcd for C₁₉H₁₇AuClOP [M + Na]: 547.0263; found: 547.0267.
ClAuPPh₂(p-F₃CC₆H₄) (4d): ¹H NMR (600 MHz, CDCl₃): δ = 7.48-7.60 (10 H, m), 7.64 (2 H, dd, J = 12.6, 7.8 Hz), 7.72 (2 H, dd, J = 7.8, 1.5 Hz). ¹³C NMR (75.5 Hz, CDCl₃): δ = 121.4 [d, J(¹³C-³¹P) = 1.2 Hz], 126.0 [dq, J(¹³C-³¹P) = 11.8 Hz, J(¹³C-¹⁹F) = 3.7 Hz], 126.7 [q, J(¹³C-¹⁹F) = 81.3 Hz], 128.0, 129.5 [d, J(¹³C-³¹P) = 11.8 Hz], 132.4 [d, J(¹³C-³¹P) = 2.5 Hz], 134.2 [d, J(¹³C-³¹P) = 8.8 Hz], 134.3 [d, J(¹³C-³¹P) = 14.3 Hz]. ³¹P NMR (121.5 Hz, CDCl₃): δ = 33.3. IR (neat, ATR): 1436, 1395, 1322, 1125, 1103, 1061, 1014, 838, 748, 708 cm^-1. ESI-HRMS: m/z calcd for C₁₉H₁₄AuClF₃P [M + Na]: 585.0031; found: 585.0032.
ClAuPPh₂(o-MeC₆H₄) (4h): ¹H NMR (600 MHz, CDCl₃): δ = 2.53 (3 H, s), 6.74 (1 H, ddd, J = 12.7, 7.7, 1.2 Hz), 7.18 (1 H, dd, J = 7.5, 7.5 Hz), 7.29-7.33 (1 H, m), 7.43 (1 H, ddd, J = 7.5, 7.5, 1.4 Hz), 7.46-7.51 (4 H, m), 7.53-7.60 (6 H, m). ¹³C NMR (75.5 Hz, CDCl₃): δ = 22.6 [d, J(¹³C-³¹P) = 12.2 Hz], 126.3 [d, J(¹³C-³¹P) = 10.0 Hz], 126.8 [d, J(¹³C-³¹P) = 60.2 Hz], 128.0 [d, J(¹³C-³¹P) = 63.8 Hz], 129.4 [d, J(¹³C-³¹P) = 12.2 Hz], 131.8 [d, J(¹³C-³¹P) = 2.2 Hz], 132.0 [d, J(¹³C-³¹P) = 9.3 Hz], 132.1 [d, J(¹³C-³¹P) = 2.2 Hz], 133.0 [d, J(¹³C-³¹P) = 8.6 Hz], 134.5 [d, J(¹³C-³¹P) = 14.3 Hz], 142.0 [d, J(¹³C-³¹P) = 12.2 Hz]. ³¹P NMR (121.5 Hz, CDCl₃): δ = 32.1. IR (neat, ATR): 1589, 1479, 1436, 1101, 997, 804, 751, 714 cm^-1. Anal. Calcd for C₁₉H₁₇AuClP: C, 44.86; H, 3.37; Cl, 6.97. Found: C, 45.00; H, 3.60; Cl, 6.93. ESI-HRMS: m/z calcd for C₁₉H₁₇AuClP [M + Na]: 531.0314; Found: 531.0314.
¹H, ¹³C, and ³¹P NMR chemical shifts are reported relative to CDCl₃ and 85% H₃PO₄.

16

General Procedure for Hydroamination of Allenes
To a suspension of [AuClPPh₂(o-tolyl)] (25.4 mg, 0.05 mmol) in toluene (0.5 mL) was added morpholine (43.7 mg, 0.502 mmol). To the reaction mixture was added 4-methyl-phenylallene (1a, 79.3 mg, 0.6 mmol) and the resulting mixture was stirred at 80 °C under an Ar atmosphere. The reaction mixture was colorless and heterogeneous at the beginning, but it turned yellow to brown as the reaction progressed. After the reaction was completed (12 h), the reaction mixture was filtered through short Florisil^® gel pad with EtOAc as an eluent and the resulting filtered solution was concentrated. The product was purified by column chromatography (basic silica gel, hexane-EtOAc = 100:1 to 10:1) to give 3a in 83% yield (90.8 mg).

17

(E)-4-(3-p-Tolylallyl)morpholine (3a): ¹H NMR (300 MHz, CDCl₃): δ = 2.31 (3 H, s), 2.40-2.59 (4 H, m), 3.12 (2 H, dd, J = 6.8, 1.3 Hz), 3.72 (4 H, dd, J = 4.7, 4.7 Hz), 6.18 (1 H, dt, J = 15.8, 6.8 Hz), 6.48 (1 H, d, J = 15.8 Hz), 7.10 (2 H, d, J = 8.1 Hz), 7.25 (2 H, d, J = 8.1 Hz). ¹³C NMR (75.5 Hz, CDCl₃): δ = 21.2, 53.7, 61.5, 67.0, 124.9, 126.2, 129.3, 133.3, 134.0, 137.4. IR (neat): 1712, 1512, 1452, 1116, 1006, 968, 869, 809, 776 cm^-1. HRMS (EI): m/z calcd for C₁₄H₁₉NO [M⁺]: 217.1462; found: 217.1464. 4-Cinnamylmorpholine (3b): ¹H NMR (300 MHz, CDCl₃): δ = 2.45 (4 H, dd, J = 4.6, 4.6 Hz), 3.10 (2 H, dd, J = 6.8, 1.3 Hz), 3.68 (4 H, dd, J = 4.6, 4.6 Hz), 6.19 (1 H, dt, J = 15.8, 6.8 Hz), 6.47 (1 H, d, J = 15.8 Hz), 7.11-7.38 (5 H, m). ¹³C NMR (75.5 Hz, CDCl₃): δ = 53.7, 61.5, 66.9, 125.8, 126.3, 127.6, 128.6, 133.5, 136.7. IR (neat): 1598, 1496, 1451, 1277, 1115, 1006, 966, 868, 741 cm^-1. HRMS (EI): m/z calcd for C₁₃H₁₇NO [M⁺]: 203.1305; found: 203.1308.
(E)-4-(4-Phenylbut-2-enyl)morpholine (3c): ¹H NMR (300 MHz, CDCl₃): δ = 2.30-2.54 (4 H, m), 2.95 (2 H, dd, J = 6.6, 0.9 Hz), 3.36 (2 H, d, J = 6.6 Hz), 3.70 (4 H, dd, J = 4.8, 4.8 Hz), 5.54 (1 H, dtt, J = 15.2, 6.6, 1.3 Hz), 5.76 (1 H, dtt, J = 15.2, 6.6, 1.3 Hz), 7.11-7.23 (3 H, m), 7.23-7.33 (2 H, m). ¹³C NMR (75.5 Hz, CDCl₃): δ = 38.9, 53.5, 61.1, 67.0, 126.1, 127.3, 128.4, 128.5, 133.4, 140.2. IR (neat): 1603, 1495, 1453, 1116, 1003, 975, 865, 745 cm^-1. HRMS (EI): m/z calcd for C₁₄H₁₉NO [M⁺]: 217.1462; found: 217.1464.
(E)-4-(Undec-2-enyl)morpholine (3d): ¹H NMR (300 MHz, CDCl₃): δ = 0.81 (3 H, t, J = 6.6 Hz), 1.03-1.43 (12 H, m), 1.95 (2 H, dt, J = 7.0, 6.6 Hz), 2.26-2.48 (4 H, m), 2.86 (2 H, d, J = 6.6 Hz), 3.65 (4 H, dd, J = 4.6, 4.6 Hz), 5.39 (1 H, dt, J = 15.2, 6.6 Hz), 5.54 (1 H, dt, J = 15.2, 6.6 Hz). ¹³C NMR (75.5 Hz, CDCl₃): δ = 14.1, 22.7, 29.2, 29.2, 29.3, 29.4, 31.9, 32.3, 53.5, 61.4, 67.0, 125.6, 135.3. IR (neat): 1720, 1454, 1004, 972, 867 cm^-1. HRMS (EI): m/z calcd for C₁₅H₂₉NO [M⁺]: 239.2244; found: 239.2246.
(E)-4-(3-Cyclohexylallyl)morpholine (3e): ¹H NMR (300 MHz, CDCl₃): δ = 0.98-1.31 (5 H, m), 1.55-1.85 (5 H, m), 1.85-2.03 (1 H, m), 2.34-2.55 (4 H, m), 2.93 (2 H, d, J = 6.8 Hz), 3.71 (4 H, dd, J = 4.7, 4.7 Hz), 5.40 (1 H, dtd, J = 15.4, 6.6, 0.9 Hz), 5.55 (1 H, dd, J = 15.4, 6.6 Hz). ¹³C NMR (75.5 Hz, CDCl₃): δ = 26.0, 26.1, 32.9, 40.5, 53.5, 61.5, 67.0, 123.0, 141.1. IR (neat): 1718, 1449, 1118, 1005, 971, 866 cm^-1. HRMS (EI): m/z calcd for C₁₃H₂₃NO [M⁺]: 209.1775; found: 209.1779.
(E)-4-(4,4-Dimethylpent-2-enyl)morpholine (3f): ¹H NMR (300 MHz, CDCl₃): δ = 0.94 (9 H, s), 2.27-2.44 (4 H, m), 2.87 (2 H, dd, J = 6.8, 1.0 Hz), 3.66 (4 H, dd, J = 4.7, 4.7 Hz), 5.32 (1 H, dt, J = 15.6, 6.8 Hz), 5.56 (1 H, d, J = 15.6 Hz). ¹³C NMR (75.5 Hz, CDCl₃): δ = 29.6, 29.7, 53.5, 61.5, 67.0, 120.3, 146.2. IR (neat): 1732, 1454, 1260, 1119, 1005, 975, 868 cm^-1. ESI-HRMS: m/z calcd for C₁₁H₂₁NO [M + H]: 184.1696; found: 184.1696.
(E)-4-(4-Phenylbut-3-en-2-yl)morpholine (3g): ¹H NMR (300 MHz, CDCl₃): δ = 1.24 (3 H, d, J = 6.6 Hz), 2.54 (4 H, dt, J = 4.8, 4.4 Hz), 3.00 (2 H, dq, J = 8.1, 6.6 Hz), 3.71 (4 H, dd, J = 4.4, 4.4 Hz), 6.15 (1 H, dt, J = 15.8, 8.1 Hz), 6.44 (1 H, d, J = 15.8 Hz), 7.14-7.42 (5 H, m). ¹³C NMR (75.5 Hz, CDCl₃): δ = 17.8, 50.8, 63.1, 67.2, 126.2, 127.5, 128.6, 131.2, 132.1, 136.9. IR (neat): 1600, 1494, 1447, 1265, 1116, 963, 864, 747 cm^-1. HRMS (EI): m/z calcd for C₁₄H₁₉NO [M⁺]: 217.1462; found: 217.1465.
(E)-4-(1-Phenylbut-2-enyl)morpholine (3g′): ¹H NMR (300 MHz, CDCl₃): δ = 1.59 (3 H, dd, J = 6.0, 1.1 Hz), 2.15-2.31 (2 H, m), 2.33-2.56 (2 H, m), 3.48 (1 H, d, J = 8.6 Hz), 3.61 (4 H, dd, J = 4.4, 4.4 Hz), 5.45 (1 H, ddd, J = 15.0, 8.6, 1.1 Hz), 5.58 (1 H, dq, J = 15.0, 6.0 Hz), 7.11-7.31 (5 H, m). ¹³C NMR (75.5 Hz, CDCl₃): δ = 17.8, 52.0, 67.2, 74.6, 127.0, 127.7, 127.9, 128.5, 132.7, 142.3. IR (neat): 1492, 1449, 1271, 1116, 1003, 967, 875, 755 cm^-1. ESI-HRMS: m/z calcd for C₁₄H₁₉NO [M + H]: 218.1539; found: 218.1539.
4-(3-Phenylbut-2-enyl)morpholine (3h): inseparable stereoisomeric mixture. ¹H NMR (300 MHz, CDCl₃): δ = 2.05 (E- and Z-3 H, s), 2.25-2.42 (Z-4 H, m), 2.44-2.60 (E-4 H, m), 2.91 (Z-2 H, d, J = 6.8 Hz), 3.17 (E-2 H, d, J = 6.8 Hz), 3.70 (Z-4 H, dd, J = 4.6, 4.6 Hz), 3.72 (E-4 H, dd, J = 4.6, 4.6 Hz), 5.55 (Z-1 H, td, J = 6.8, 1.3 Hz), 5.86 (E-1 H, td, J = 6.8, 1.3 Hz), 7.09-7.45 (E- and Z-5 H, m).
NOE Experiment for 3h: Two signals were observed by irradiation for Me peak (δ = 2.05 ppm); 0.52% for allyl-H peak of E-isomer (δ = 3.17 ppm) and 1.64% for vinyl-H peak of Z-isomer (δ = 5.55 ppm). From this experiment, we determined that the major product was E-isomer and the E:Z ratio was 5: 4.