Synthesis of Propargylamines by a Copper-Catalyzed Tandem Anti-Markovnikov Hydroamination and Alkyne Addition

Abstract

A highly efficient tandem anti-Markovnikov hydroamination and alkyne addition reaction catalyzed by a Cu(I) or Cu(II) catalyst was developed. Various propargylamines were obtained in moderate to good yields. This tandem process provides a novel and simple approach to propargylamine derivatives from alkynes and amines.

Key words

copper - hydroamination - propargylamine - alkynes - amines

References and Notes

• For recent reviews on catalytic hydroamination, see:
• 1a Odom AL. Dalton Trans.  2005,  225 
• 1b Hultzsch KC. Adv. Synth. Catal.  2005,  347:  367 
• 1c Hong S. Marks TJ. Acc. Chem. Res.  2004,  37:  673 
• 1d Doye S. Synlett  2004,  1653 
• 1e Roesky PW. Müller TE. Angew. Chem. Int. Ed.  2003,  42:  2708 
• 1f Bytschkov I. Doye S. Eur. J. Org. Chem.  2003,  935 
• 1g Pohlki F. Doye S. Chem. Soc. Rev.  2003,  32:  104 
• 1h Alonso F. Beletskaya IP. Yus M. Chem. Rev.  2004,  104:  3079 
• 1i Severin R. Doye S. Chem. Soc. Rev.  2007,  36:  1407 
• 1j Müller TE. Hultzsch KC. Yus M. Foubelo F. Tada M. Chem. Rev.  2008,  108:  3795 
• 2a Trost BM. Angew. Chem., Int. Ed. Engl.  1995,  34:  259 
• 2b Trost BM. Science  1991,  254:  1471 
• 3a Castro CE. Stephens RD. J. Org. Chem.  1963,  28:  2163 
• 3b Stephens RD. Castro CE. J. Org. Chem.  1963,  28:  3313 
• 4a Xu L. Lewis IR. Davidsen SK. Summers JB. Tetrahedron Lett.  1998,  39:  5159 
• 4b Müller TE. Grosche M. Herdtweck E. Pleier AK. Walter E. Yan YK. Organometallics  2000,  19:  170 
• 4c Peng C. Cheng J. Wang J. Adv. Synth. Catal.  2008,  350:  2359 
• 4d Müller TE. Pleier A.-K. J. Chem. Soc., Dalton Trans.  1999,  583 
• 4e Kamijo S. Jin T. Yamamoto Y. Angew. Chem. Int. Ed.  2002,  41:  1780 
• 4f Xu L. Lewis IR. Davidsen SK. Summers JB. Tetrahedron Lett.  1998,  39:  5159 
• 5a Fukumoto Y. Asai H. Shimizu M. Chatani N. J. Am. Chem. Soc.  2007,  129:  13792 
• 5b Tzalis D. Koradin C. Knochel P. Tetrahedron Lett.  1999,  40:  6193 
• 5c Park YJ. Kwon B.-I. Ahn J.-A. Jun C.-H. J. Am. Chem. Soc.  2004,  126:  13892 
• 6a Yao X. Li C.-J. Org. Lett.  2005,  7:  4395 
• 6b Wei C. Mague JT. Li C.-J. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5749 
• 6c Wei C. Li C.-J. J. Am. Chem. Soc.  2003,  125:  9584 
• 6d Wei C. Li Z. Li C.-J. Org. Lett.  2003,  5:  4473 
• 6e Wei C. Li C.-J. Green Chem.  2002,  4:  39 
• 6f Wei C. Li C.-J. J. Am. Chem. Soc.  2002,  124:  5638 
• 6g Li C.-J. Wei C. Chem. Commun.  2002,  268 
• 6h Zhang J. Wei C. Li C.-J. Tetrahedron Lett.  2002,  43:  5731 
• 6i Huang B. Yao X. Li C.-J. Adv. Synth. Catal.  2006,  348:  1528 
• 6j Yao X. Li C.-J. Org. Lett.  2006,  8:  1953 
• 6k Deng G. Li C.-J. Synlett  2008,  10:  1571 
• 6l Viswanathan G. Li C.-J. Tetrahedron Lett.  2002,  43:  1613 
• For recent examples, see:
• 7a Asano Y. Hara K. Ito H. Sawamura M. Org. Lett.  2007,  9:  3901 
• 7b Colombo F. Benaglia M. Orlandi S. Usuelli F. Celentano G. J. Org. Chem.  2006,  71:  2064 
• 7c Arimitsu S. Hammond GB.
  J. Org. Chem.  2006,  71:  8665 
• 7d Gommermann N. Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2003,  42:  5763 
• 7e Koradin C. Gommermann N. Polborn K. Knochel P. Chem. Eur. J.  2003,  9:  2797 
• 7f Lu G. Li X. Chan WL. Chan ASC. Chem. Commun.  2002,  172 
• 7g Chen ZL. Xiong WN. Jiang B. Chem. Commun.  2002,  2098 
• 7h Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2002,  41:  2535 
• 7i Carreira EM. Acc. Chem. Res.  2000,  33:  373 ; and references therein
• 8a Zhou L. Jiang H.-F. Li C.-J. Adv. Synth. Catal.  2008,  350:  2226 
• For our works on silver- and gold-catalyzed hydroamination of alkynes, see:
• 8b Luo Y. Li Z. Li C.-J. Org. Lett.  2005,  7:  2675 
• 8c Zhang Y. Donahue JP. Li C.-J. Org. Lett.  2007,  9:  627 
• For references on copper-catalyzed intermolecular hydroamination of olefins, see:
• 9a Munro-Leighton C. Blue ED. Gunnoe TB. J. Am. Chem. Soc.  2006,  128:  1446 
• 9b Taylor J. Whittall N. Hii K.-K. Org. Lett.  2006,  8:  3561 
• For recent examples, see:
• 10a Katagiri T. Tsurugi H. Satoh T. Miura M. Chem. Commun.  2008,  3405 
• 10b Nishimura T. Guo X.-X. Ohnishi K. Hayashi T. Adv. Synth. Catal.  2007,  349:  2669 
• 10c Tsukada N. Ninomiya S. Aoyama Y. Inoue Y. Org. Lett.  2007,  9:  2919 
• 10d Weng W. Guo C. Celenligil-Cetin R. Foxman BM. Ozerov OV. Chem. Commun.  2006,  197 
• 10e Munro-Leighton C. Delp SA. Alsop NM. Blue ED. Gunnoe TB. Chem. Commun.  2008,  111 
• 11a Zani L. Eichhorn T. Bolm C. Chem. Eur. J.  2007,  13:  2587 
• 11b Aschwanden P. Stephenson CRJ. Carreira EM. Org. Lett.  2006,  8:  2437 

12

Representative Experimental Procedure Copper(I) bromide (3.6 mg, 0.025 mmol, 5 mol%) was suspended in toluene (2 mL) in a 10 mL Schlenk tube under nitrogen. Then, diallylamine (49 mg, 0.5 mmol) and phenylacetylene (204 mg, 2 mmol) were added. The resulting solution was stirred at 100 ˚C for 24 h. After cooling to r.t., the resulting mixture was filtered through a short path of SiO₂ in a pipette eluting with EtOAc. The volatiles were removed in vacuo, and the residue was purified by column chromatography (SiO₂, hexane-EtOAc, 10:1) to give 3a (111.3 mg, 74%) as a pale yellow oil. ^¹H NMR (400 MHz, CDCl₃): δ = 7.42-7.39 (m, 2 H), 7.31-7.23 (m, 8 H), 5.88-5.79 (m, 2 H), 5.23 (d, J = 17.2 Hz, 2 H), 5.13 (d, J = 10.0 Hz, 2 H), 3.97 (t, J = 7.6 Hz, 1 H), 3.41(dt, J = 14.0, 2.4 Hz, 2 H), 3.11-2.97 (m, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 139.0, 136.6, 131.8, 129.7, 128.4, 128.3, 128.1, 126.5, 123.6, 117.5, 87.7, 86.2, 55.4, 54.3, 40.6. MS (70 eV): m/z (%) = 301 [M⁺], 274, 242, 215, 210(100), 191, 168, 154, 128, 115, 91. HRMS (EI): m/z calcd for C₂₂H₂₃N [M⁺]: 301.1831; found: 301.1814.
The experiments in Table  [²] were carried out analogously. All products were purified by column chromatography and characterized by NMR spectroscopy and standard/high-resolution mass spectrometry.