Synlett 2008(10): 1515-1519  
DOI: 10.1055/s-2008-1077790
LETTER
© Georg Thieme Verlag Stuttgart · New York

Facile and Selective Synthesis of Propargylic Amines and 1,6-Diynes: One-Pot Three-Component Coupling Reactions of Alkynylsilanes, Aldehydes and Amines by a Cooperative Catalytic System Comprised of CuCl and Cu(OTf)2

Norio Sakai*, Naoki Uchida, Takeo Konakahara
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science (RIKADAI), Noda, Chiba 278-8510, Japan
e-Mail: sakachem@rs.noda.tus.ac.jp;
Further Information

Publication History

Received 10 March 2008
Publication Date:
16 May 2008 (online)

Abstract

Described herein is a three-component coupling reaction of alkynylsilanes, aldehydes and amines by a cooperative catalytic system comprised of CuCl and Cu(OTf)2, leading to the production of a variety of propargyl amine derivatives. This catalytic system was successfully applied to the practical preparation of 1,6-diyne derivatives via twice-performed, domino-type coupling reactions.

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9

General Procedure for the Synthesis of a Propargyl Amine: To a MeCN solution (300 µL) in a screw-capped vial under an N2 atmosphere, alkynylsilane 1 (0.45 mmol), aldehyde 2 (0.30 mmol), amine 3 (0.36 mmol), Cu(OTf)2 (5.4 mg, 0.015 mmol) and CuCl (1.5 mg, 0.015 mmol) were successively added, and the vial was sealed with a cap containing a PTFE septum. The reaction mixture was heated at 100 °C until the reaction was completed as monitored by TLC. After the reaction, the mixture was directly subjected to SiO2 gel without the usual extraction, and was purified by flash column chromatography (hexane-EtOAc) to give the corresponding propargyl amines in the yields shown in Table [2] .
1-[1-(4-Methoxyphenyl)-3-phenylpropyn-2-yl]-4-methyl-
piperazine (13): pale yellow oil. 1H NMR (500 MHz, CDCl3): δ = 2.21 (s, 3 H), 2.40 (m, 4 H), 2.59 (m, 4 H), 3.74 (s, 3 H), 4.69 (s, 1 H), 6.82 (d, J = 7.5 Hz, 2 H), 7.23 (m, 3 H), 7.42 (m, 2 H), 7.46 (d, J = 7.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 46.0, 48.8, 55.3, 55.3, 61.0, 85.7, 88.1, 113.4, 113.5, 123.2, 128.0, 128.2, 129.6, 130.4, 131.8, 159.1. MS (EI): m/z = 320. HRMS (FAB): m/z calcd for C21H24N2O: 320.1889; found: 320.1876.
N-(tert-Butyl)-1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-amine (17): colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.26 (s, 9 H), 3.80 (s, 3 H), 4.80 (s, 1 H), 6.89 (d, J = 7.5 Hz, 2 H), 7.29 (m, 3 H), 7.42 (m, 2 H), 7.51 (d, J = 7.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 29.9, 48.2, 51.2, 55.3, 84.1, 92.8, 113.9, 123.6, 127.9, 128.2, 128.5, 131.4, 135.0, 158.9. MS (EI): m/z = 293. HRMS (FAB): m/z calcd for C20H23NO: 293.1780; found: 293.1785.

10

When a similar coupling reaction was carried out with phenylacetylene, propargylic amine 4 was obtained in a 61% yield (7 h).

12

General Procedure for the Synthesis of a Symmetrical 1,6-Diyne: To a MeCN solution (300 µL) in a screw-capped vial under a N2 atmosphere, alkynylsilane 1 (0.90 mmol), paraformaldehyde 2h (0.90 mmol), primary amine 3 (0.30 mmol), Cu(OTf)2 (5.4 mg, 0.015 mmol) and CuCl (1.5 mg, 0.015 mmol) were successively added, and the vial was sealed with a cap containing a PTFE septum. The reaction mixture was heated at 100 °C for 24 h. After the reaction, the mixture was directly subjected to SiO2 gel without the usual extraction, and was purified by flash column chromatography (hexane-EtOAc) to give the corresponding 1,6-diynes in the yields shown in Table [3] .
N-Benzyl-N,N-bis[3-(tert-butyldimethylsilyl)propyn-2-yl]amine (27): colorless oil. 1H NMR (500 MHz, CDCl3):
δ = 0.12 (s, 12 H), 0.96 (s, 18 H), 3.40 (s, 4 H), 3.69 (s, 2 H), 7.32 (m, 5 H). 13C NMR (125 MHz, CDCl3): δ = -4.5, 16.5, 26.1, 43.1, 56.9, 88.2, 101.7, 127.3, 128.3, 129.4, 138.0. MS (EI): m/z = 411. HRMS (FAB): m/z calcd for C25H42NSi2: 412.2856; found: 412.2866.

14

Procedure for the Synthesis of 1-Aminoindolizine 9′: To a MeCN solution (300 µL) in a screw-capped vial under a N2 atmosphere, alkynylsilane 1a (78 mg, 0.45 mmol), aldehyde 2g (48 mg, 0.45 mmol), amine 3a (26 mg, 0.30 mmol) and Cu(OTf)2 (5.4 mg, 0.015 mmol) were successively added, and the vial was sealed with a cap containing a PTFE septum. The reaction mixture was heated at 100 °C for 1 h. After the reaction, the mixture was directly subjected to Al2O3 gel without the usual extraction, and was purified by flash column chromatography (hexane-EtOAc) to give 1-aminoindolizine 9′ in 97% yield (80 mg).
3-Phenyl-1-piperidin-1-ylindolizine (9′): yellow oil. 1H NMR (500 MHz, CDCl3): δ = 1.50 (quint, J = 6.0 Hz, 2 H), 1.71 (quint, J = 6.0 Hz, 4 H), 2.94 (t, J = 6.0 Hz, 4 H), 6.30 (t, J = 7.5 Hz, 1 H), 6.44 (t, J = 7.5 Hz, 1 H), 6.60 (s, 1 H), 7.22 (t, J = 7.5 Hz, 1 H), 7.36 (m, 3 H), 7.47 (d, J = 7.0 Hz, 2 H), 8.11 (d, J = 7.5 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 24.4, 26.5, 55.2, 105.7, 110.7, 114.3, 118.1, 121.6, 126.7, 127.5, 127.7, 128.6, 128.9, 131.1, 132.6. MS (EI): m/z = 276.