Organocatalytic Synthesis of Terminal Propargylamine Derivatives by Tandem Amination-Alkynylation

Abstract

The first organocatalytic synthesis of terminal propargylic amines from aldehydes via tandem amination/Seyferth-­Gilbert alkynylation has been developed. The described protocol provides the formal addition products of acetylene (HC≡CH) to ali­phatic imines, which are not easily obtained directly.

Key words

amination - organocatalysis - Seyferth-Gilbert alkynylation - tandem reactions - terminal propargylamines

References and Notes

• For reviews, see:
• 1a Trost BM. Weiss AH. Adv. Synth. Catal.  2009,  351:  963 
• 1b Zani L. Bolm C. Chem. Commun.  2006,  4263 
• 2 Wright JL. Gregory TF. Kesten SP. Boxer PA. Serpa KA. Meltzer LT. Wise LD. Espitia SA. Konkoy CS. Whittemore ER. Woodward RM. J. Med. Chem.  2000,  43:  3408 
• For selected examples, see:
• 3a Wei C.-M. Li C.-J. J. Am. Chem. Soc.  2002,  124:  5638 
• 3b Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2002,  41:  2535 
• 3c Gommermann N. Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2003,  42:  5763 
• 3d Knopfel TF. Aschwanden P. Ichikawa T. Watanabe T. Carreira EM. Angew. Chem. Int. Ed.  2004,  42:  5971 
• 3e Wei C.-M. Mague JT. Li C.-J. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5749 
• 3f Colombo F. Benaglia M. Orlandi S. Usuelli F. J. Mol. Catal. A: Chem.  2006,  260:  128 
• 3g Colombo F. Benaglia M. Orlandi S. Usuelli F. Celentano G. J. Org. Chem.  2006,  71:  2064 
• 3h Dodda R. Zhao C.-G. Org. Lett.  2007,  9:  165 
• 3i Dodda R. Zhao C.-G. Tetrahedron Lett.  2007,  48:  4339 
• 3j Ji J.-X. Yeung TTLA. Wu J. Yip CW. Chan ASC. Adv. Synth. Catal.  2004,  346:  42 
• 3k Ji J.-X. Wu J. Chan ASC. Proc. Natl. Acad. Sci. U.S.A.  2005,  102:  11196 
• 3l Zhou L. Jiang H.-F. Li C.-J. Adv. Synth. Catal.  2008,  350:  2226 
• 3m Bisai A. Singh VK. Org. Lett.  2006,  8:  2405 
• 3n Rueping M. Antonchick AP. Brinkmann C. Angew. Chem. Int. Ed.  2007,  46:  6903 
• 3o Blay G. Cardona L. Climent E. Pedro JR. Angew. Chem. Int. Ed.  2008,  47:  5593 
• 3p Irmaka M. Boysena MMK. Adv. Synth. Catal.  2008,  350:  403 
• 3q Hatano M. Asai T. Ishihara K. Tetrahedron Lett.  2008,  49:  379 
• 3r Liu J. Liu B. Jia X. Li X. Chan ASC. Tetrahedron: Asymmetry  2007,  18:  396 
• 3s Wang J. Shao Z.-H. Ding K. Yu WY. Chan ASC. Adv. Synth. Catal.  2009,  351:  1250 
• 3t Lu Y.-D. Johnstone TC. Arndtsen BA. J. Am. Chem. Soc.  2009,  131:  11284 ; see also ref. 5
• For general reviews, see:
• 4a Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 
• 4b Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 
• 4c Dalko PI. Enantioselective Organocatalysis: Reactions and Experimental Procedures   Wiley-VCH; Weinheim: 2007. 
• 4d Berkessel A. Groger H. Asymmetric Organocatalysis-From Biomimetic Concepts to Powerful Methods for Asymmetric Synthesis   Wiley-VCH; Weinheim: 2005. 
• 4e Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 
• For excellent examples of metal-catalyzed synthesis of propargylic amines using silylacetylene as pre-nucleophiles, see:
• 5a Fischer C. Carreira EM. Org. Lett.  2001,  3:  4319 
• 5b Gommermann N. Knochel P. Chem. Commun.  2004,  2324 
• 5c Gommermann N. Knochel P. Tetrahedron  2005,  61:  11418 
• 5d Traverse JF. Hoveyda AH. Snapper ML. Org. Lett.  2003,  5:  3273 
• 6a Shao Z.-H. Pu X.-W. Li X.-J. Fan B.-M. Chan ASC. Tetrahedron: Asymmetry  2009,  20:  225 
• 6b Shao Z.-H. Wang J. Ding K. Chan ASC. Adv. Synth. Catal.  2007,  349:  2375 
• 6c Shao Z.-H. Chan ASC. Synthesis  2008,  2868 
• For a general review on chiral primary amine-catalyzed reactions, see:
• 7a For examples, see: Peng F.-Z. Shao Z.-H. J. Mol. Catal. A: Chem.  2008,  285:  1 
• 7b Peng F.-Z. Shao Z.-H. Fan B.-M. Song H. Li G.-P. Zhang H.-B.
  J. Org. Chem.  2008,  73:  5202 
• 7c Peng F.-Z. Shao Z.-H. Pu X.-W. Zhang H.-B. Adv. Synth. Catal.  2008,  350:  2199 
• 7d Pu X.-W. Li P.-H. Peng F.-Z. Li X.-J. Zhang H.-B. Shao Z.-H. Eur. J. Org. Chem.  2009,  4622 
• 8 For a review on the concept of catalysis through combining transition-metals and organocatalysis, see: Shao ZH. Zhang H.-B. Chem. Soc. Rev.  2009,  38:  2745 
• 9a Bogevig A. Juhl K. Kumaragurubaran N. Zhuang W. Jorgensen KA. Angew. Chem. Int. Ed.  2002,  41:  1790 
• 9b List B. J. Am. Chem. Soc.  2002,  124:  5656 
• 9c Chowdari NS. Barbas CF. Org. Lett.  2005,  7:  867 
• 9d Suri JT. Steiner DD. Barbas CF. Org. Lett.  2005,  7:  3885 
• 9e Franzen J. Marigo M. Fielenbach D. Wabnitz TC. Kjærsgaard A. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  18296 
• 9f Marigo M. Schulte T. Franzen J. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  15710 
• 10a Ohira S. Synth. Commun.  1989,  19:  561 
• 10b Müller S. Liepold B. Roth GJ. Bestmann HJ. Synlett  1996,  521 
• 11 Jiang H. Falcicchio A. Jensen KL. Paixao MW. Bertelsen S. Jørgensen KA. J. Am. Chem. Soc.  2009,  131:  7153 
• 12 Ding H. Friestad GK. Org. Lett.  2004,  6:  637 
• 13 Coutts R, Baker G, Sloley D, Shan J, and Pang PKT. inventors; US Patent  6060516. 

14

Typical procedure for one-pot, tandem α-amination-alkynylation of aldehydes: Proline (0.1 mmol, 10 mol%) was added to a stirring solution of aldehyde 1a (1 mmol) and DIAD (1 mmol) in CH₂Cl₂ (3 mL). After 2 h of vigorous stirring at r.t., MeOH (15 mL), Ohira-Bestmann reagent (1.2 mmol, 1.2 equiv) and K₂CO₃ (2 mmol, 2 equiv) were added. After stirring for 12 h at r.t., the reaction mixture was diluted with Et₂O. The excess solvents were removed under reduced pressure and the residue was purified by flash silica gel chromatography to give the desired product 2a. IR (film): 3254, 2985, 1743, 1678, 1529, 1417, 1233, 1109 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 6.39 (br s, 1 H), 5.06 (br s, 1 H), 4.89 (sept, J = 6.2 Hz, 2 H), 2.23 (s, 1 H), 1.36 (d, J = 6.9 Hz, 3 H), 1.18 (d, J = 6.1 Hz, 12 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 156.1, 154.7, 82.1, 71.5, 70.6, 69.8, 45.8, 22.0, 21.9, 19.2; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₂H₂₀N₂O₄: 257.1496; found: 257.1490.