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.

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.