1,2-Addition of Phenylacetylene to Aldimines Catalyzed by InCl₃/CuCl in Water under Barbier Conditions

Abstract

A new and efficient method for the preparation of various propargylamines has been achieved by the simple Barbier-Grignard-type reaction of phenylacetylene with a variety of ald­imines under aqueous conditions, catalyzed by a bimetallic In-Cu system.

Key words

aldimines - water - indium chloride - copper chloride - propargylamines

References and Notes

• 1 Tuck DG. In Comprehensive Organometallic Chemistry   Vol. 1:  Wilkinson G. Pergamon Press; New York: 1982.  p.683-723  
• 2a Li C.-J. Tetrahedron  1996,  52:  5643 
• 2b Li C.-J. Chan TH. Organic Reactions in Aqueous Media   John Wiley and Sons; New York: 1997. 
• 2c Reissig HU. Organic Synthesis Highlights   VCH; Weinheim: 1991.  p.71 
• 2d Li C.-J. Chem. Rev.  1993,  93:  2023 
• 2e Sarma R. Sarmah MM. Lekhok KC. Prajapati D. Synlett  2010,  2847 
• 2f Lubineau A. Auge J. Queneau Y. Synthesis  1994,  741 
• For Barbier-type allylation using Bi, see:
• 3a Katritzky AR. Shobana N. Harris PA. Organometallics  1992,  11:  1381 
• Using Sn see:
• 3b Marton D. Stivanello D. Tagliavini G. J. Org. Chem.  1996,  61:  2731 
• Using Mg, see:
• 3c Barbot F. Miginiac P. Tetrahedron Lett.  1975,  16:  3829 
• Using Ce, see:
• 3d Imamoto T. Kashumo T. Tuosorayama Y. Mita T. Hatanaka Y. Yokayoma M. J. Org. Chem.  1984,  49:  3904 
• Using Ba, see:
• 3e Yanagisawa A. Koide T. Yoshida K. Synlett  2010,  1515 
• 4 Yamamoto Y. Asao N. Chem. Rev.  1993,  93:  2207 
• 5 Grieco PA. Organic Synthesis in Water   Blackie Academic and Professional; London: 1998. 
• For the biological significance of propargylamine, see:
• 6a Konishi M. Ohkuma H. Tsuno T. Oki T. VanDuyne G. Clardy J. J. Am. Chem. Soc.  1990,  112:  3715 
• 6b Nilsson B. Vargas HM. Ringdahl B. Hacksell U.
  J. Med. Chem.  1992,  35:  285 
• 6c Miura M. Enna M. Okuro K. Nomura M. J. Org. Chem.  1995,  60:  4999 
• 6d For a recent review, see: Cozzi PG. Hilgraf R. Zimmermann N. Eur. J. Org. Chem.  2004,  4095 
• 6e Lu Y. Johnstone TC. Arndtsen BA. J. Am. Chem. Soc.  2009,  131:  11284 
• 7a Cozzi PG. Hilgraf RN. Zimmermann N. Eur. J. Org. Chem.  2004,  4095 
• 7b Pu L. Yu HB. Chem. Rev.  2001,  101:  757 
• 8 For a recent review, see: Yamada K. Tomioka K. Chem. Rev.  2008,  108:  2874 
• For a review, see:
• 9a Pu L. Tetrahedron  2003,  59:  9873 
• For recent representative examples, see:
• 9b Gao G. Xie R.-G. Pu L. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5417 
• 9c Li Z.-B. Pu L. Org. Lett.  2004,  6:  1065 
• 9d Xu Z. Chen C. Xu J. Miao M. Yan W. Wang R. Org. Lett.  2004,  6:  1193 
• 9e Dahmen S. Org. Lett.  2004,  6:  2113 
• 9f Cozzi PG. Alesi S. Chem. Commun.  2004,  2448 
• 9g Liu L. Wang R. Kang Y.-F. Chen C. Xu Z.-Q. Zhou Y.-F. Ni M. Cai H.-Q. Gong M.-Z. J. Org. Chem.  2005,  70:  1084 
• For review, see:
• 10a Alcaide B. Almendros P. Eur. J. Org. Chem.  2002,  1595 
• 10b List B. Tetrahedron  2002,  58:  5573 
• 11a Shibasaki M. Yoshikawa N. Chem. Rev.  2002,  102:  2187 
• 11b Shibasaki M. Kanai M. Funabashi K. Chem. Commun.  2002,  1989 
• 11c Ma J.-A. Cahard D. Angew. Chem. Int. Ed.  2004,  43:  4566 
• 12 Bloch R. Chem. Rev.  1998,  98:  1407 
• 13a Kobayashi S. Ishitani H. Chem Rev.  1999,  99:  1069 
• 13b Enders D. Reinhold U. Tetrahedron: Asymmetry  1997,  8:  1895 
• 13c Brook MA. Jahangir A. Synth. Commun.  1988,  18:  893 
• 14a Traverse JF. Hoveyda AH. Snapper ML. Org. Lett.  2003,  5:  3273 
• 14b Akullian LC. Ho veyda AH. Snapper ML. Angew. Chem. Int. Ed.  2003,  42:  4244 
• 15a Wie C. Li CJ. J. Am. Chem. Soc.  2002,  124:  5638 
• 15b Wei C. Mague JT. Li C.-J. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5749 
• 16a Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2002,  41:  2535 
• 16b Gommermann N. Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2003,  42:  5763 
• 17 Jiang B. Si Y.-G. Angew. Chem. Int. Ed.  2004,  43:  216 
• For other recent reports, see:
• 18a Fischer C. Carreira EM. Org. Lett.  2001,  3:  4319 
• 18b Fischer C. Carreira EM. Org. Lett.  2004,  6:  1497 
• 18c Wei C. Li Z. Li C. Org. Lett.  2003,  5:  4473 
• 18d Park SB. Alper H. Chem. Commun.  2005,  1315 
• 19a Laskar DD. Prajapati D. Sandhu JS. Tetrahedron Lett.  2001,  42:  7883 
• 19b Laskar DD. Gohain M. PrajapatiD . Sandhu JS. New J. Chem.  2002,  26:  193 
• 19c Gohain M. Gogoi BJ. Prajapati D. Sandhu JS. New J. Chem.  2003,  27:  1038 
• 19d Borah HN. Prajapati D. Boruah RC. Synlett  2005,  2823 
• 19e Sarma R. Prajapati D. Synlett  2008,  3001 
• 21a Auge J. Lubin-Germain N. Seghrouchni L. Tetrahedron Lett.  2002,  43:  5255 
• 21b Auge J. Lubin-Germain N. Seghrouchni L. Tetrahedron Lett.  2003,  44:  819 
• 22 Kalyanam N. Rao GV. Tetrahedron Lett.  1993,  34:  1647 
• 23 Frantz DE. Fassler R. Carreira EM. J. Am. Chem. Soc.  1999,  121:  11245 
• 24 Zani L. Bolm C. Chem. Commun.  2006,  4263 ; and references cited therein
• 25a Zhang K. Huang Y. Rugu C. Tetrahedron Lett.  2010,  51:  5463 
• 25b Liu B. Huang L. Liu J. Zhong Y. Li X. Chan ASC. Tetrahedron: Asymmetry  2007,  18:  2901 
• 25c Hatano M. Asai T. Ishihara K. Tetrahedron Lett.  2008,  49:  379 

20

General Experimental Procedure for the Addition of Alkynes 1 to Aldimines 2 Aldimine 1a (0.225 g, 1 mmol) in a round-bottomed flask was treated with InCl₃ (0.0026 g, 1.2 mol%), CuCl (0.120 g, 12 mol%), phenyl acetylene (0.12 g, 1.2 mmol), and H₂O (2 mL). The mixture was then stirred at r.t. for 20 min and then at 40 ˚C for 4 h. Stirring was continued until no further increase of the reaction product as monitored by ^¹H NMR. After completion, the product was extracted with Et₂O or EtOAc (3 × 30 mL). The combined organic layers were washed with H₂O and dried over anhyd Na₂SO₄. Evaporation of the solvent gave a crude product which was subjected to column chromatography on silica gel with EtOAc-hexane (1:6) as eluent to afford exclusively the corresponding propargylamine 3a in 85% yield.
Conpound 3b: IR (liquid film): ν_max = 3410, 2230, 1615, 1510, 1325, 1185 cm^{- ¹}. ^¹H NMR (300 MHz, CDCl₃): δ = 2.20 (s, 3 H), 4.12 (br, 1 H), 5.21 (s, 1 H), 6.84-7.01 (m, 3 H), 7.18-7.36 (m, 7 H), 7.40-7.48 (m, 2 H), 7.62 (d, J = 8.5 Hz, 2 H). ^{¹ ³}C NMR (75 MHz, CDCl₃): δ = 21.3, 50.6, 85.2, 89.0, 115.1, 119.2, 123.1, 127.5, 128.3, 128.5, 129.3, 129.6, 132.1, 137.2, 138.2, 146.8. MS: m/z = 297 [M⁺].

Compound 3h: mp 185-86 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 2.24 (s, 3 H), 4.83 (br, 1 H), 5.48 (d, 1 H), 7.18-7.24
(m, 2 H), 7.32-7.48 (m, 8 H), 7.59-7.65 (m, 2 H), 7.76 (d, J = 8.5 Hz, 2 H). ^{¹ ³}C NMR (75 MHz, CDCl₃): δ = 21.4, 50.1, 85.6, 87.2, 120.0, 127.2, 127.6, 128.2, 128.6, 128.8, 129.0, 129.6, 131.5, 137.4, 137.8, 144.5. MS: m/z = 361 [M⁺].
Compound 3j: mp 192-193 ˚C, ^¹H NMR (300 MHz, CDCl₃): δ = 2.28 (s, 3 H), 2.34 (s, 3 H), 4.82 (br, 1 H), 5.42 (d, 1 H), 7.10-7.31 (m, 9 H), 7.38 (d, J = 8.5 Hz, 2 H), 7.68 (d, J = 8.5 Hz, 2 H). ^{¹ ³}C NMR (75 MHz, CDCl₃): δ = 21.3, 21.7, 50.2, 85.6, 87.0, 121.3, 127.1, 127.8, 128.4, 129.0, 129.2, 129.8, 130.2, 132.0, 136.2, 137.4, 138.6, 145.8. MS: m/z = 375 [M⁺].
Compound 3k: mp 197-199 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 2.33 (s, 3 H), 4.80 (br, 1 H), 5.50 (d, 1 H), 7.19-7.42 (m, 10 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.70 (d, J = 8.5 Hz, 2 H). ^{¹ ³}C NMR (75 MHz, CDCl₃): δ = 21.8, 49.8, 85.6, 87.0, 121.2, 127.0, 127.8, 128.4, 128.6, 129.1, 129.2, 129.8, 130.2, 132.1, 136.2, 137.3, 138.6, 145.8. MS: m/z = 361 [M⁺].