Simple and General Procedure for the Synthesis of α,β-Alkynyl Ketones from Nitriles Using Alkynyldimethylaluminum Reagents

Balaji L. Korbad; Sang-Hyeup Lee

doi:10.1055/s-0033-1339482

Synlett, Table of Contents

Synlett 2013; 24(15): 1953-1958
DOI: 10.1055/s-0033-1339482

letter

Simple and General Procedure for the Synthesis of α,β-Alkynyl Ketones from Nitriles Using Alkynyldimethylaluminum Reagents

Balaji L. Korbad

Department of Life Chemistry, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk 712-702, Korea Fax: +82(53)8503728 Email: leeshh@cu.ac.kr

,

Sang-Hyeup Lee*

Department of Life Chemistry, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk 712-702, Korea Fax: +82(53)8503728 Email: leeshh@cu.ac.kr

› Author Affiliations

Abstract

All articles of this category

Abstract

A simple and efficient approach for the synthesis of α,β-alkynyl ketones from nitriles and alkynyldimethylaluminum reagents, derived from trimethylaluminum and alkynes, is described. This methodology provides access to a wide range of α,β-alkynyl ketones with aliphatic, aromatic, and heteroaromatic substituents in moderate to high yield (53–90%). In the cases of aryl-substituted nitriles, the product can also be obtained as α,β-alkynyl N-H ketimines in high yield (88–93%).

Key words

α,β-alkynyl ketones - α,β-alkynyl N-H ketimines - alkynes - trimethylaluminum - nitriles

Full Text

References

References and Notes

1a Savarin CG, Murry JA, Dormer PG. Org. Lett. 2002; 4: 2071
1b Karpov AS, Müller TJ. J. Org. Lett. 2003; 5: 3451

2a Vong BG, Kim SH, Abraham S, Theodorakis EA. Angew. Chem. Int. Ed. 2004; 43: 3947
2b Trost BM, Ball ZT. J. Am. Chem. Soc. 2004; 126: 13942

3a Chang K.-T, Choi Y.-H, Kim S.-H, Yoon Y.-J, Lee W.-S. J. Chem. Soc., Perkin Trans. 1 2002; 207
3b Kel’in AV, Gevorgyan V. J. Org. Chem. 2002; 67: 95
3c Sheng H, Lin S, Huang Y. Tetrahedron Lett. 1986; 27: 4893
3d Jeevanandam A, Narkunan K, Cartwright C, Ling Y.-C. Tetrahedron Lett. 1999; 40: 4841

For some recent examples, see:

4a Ge G.-C, Mo D.-L, Ding C.-H, Dai L.-X, Hou X.-L. Org. Lett. 2012; 14: 5756
4b Shao J, Huang X, Hong X, Liu B, Xu B. Synthesis 2012; 44: 1798
4c Shen Y, Cai S, He C, Lin X, Lu P, Wang Y. Tetrahedron 2011; 67: 8338
4d Fu MY, Guo J, Toy PH. Synlett 2011; 989

5a Kalinin VN, Shostakovsky MV, Ponomaryov AB. Tetrahedron Lett. 1990; 31: 4073
5b Ciattini PG, Morera E, Ortar G, Rossi SS. Tetrahedron 1991; 47: 6449
5c Torii S, Okumoto H, Xu L.-H, Sadakane M, Shostakovsky MV, Ponomaryov AB, Kalinin VN. Tetrahedron 1993; 49: 6773
5d Dodero VI, Koll LC, Faraoni MB, Mitchell TN, Podesta JC. J. Org. Chem. 2003; 68: 10087
5e Ryabukhin DS, Sorokoumov VN, Savicheva EA, Boyarskiy VP, Balova IA, Vasilyev AV. Tetrahedron Lett. 2013; 54: 2369

6a Trost BM, Schmidt T. J. Am. Chem. Soc. 1988; 110: 2301
6b Cabarrocas G, Ventura M, Maestro M, Mahia J, Villalgordo JM. Tetrahedron: Asymmetry 2000; 11: 2483

7a Ahmed MS. M, Mori A. Org. Lett. 2003; 5: 3057
7b Liang B, Huang M, You Z, Xiong Z, Lu K, Fathi R, Chen J, Yang Z. J. Org. Chem. 2005; 70: 6097
7c Rahman MT, Fukuyama T, Kamata N, Sato M, Ryu I. Chem. Commun. 2006; 2236
7d Tambade PJ, Patil YP, Nandurkar NS, Bhanage BM. Synlett 2008; 886

8 Shen Q, Huang W, Wang J, Zhou X. Organometallics 2008; 27: 301

9a Maruoka K, Yamamoto H. Angew. Chem., Int. Ed. Engl. 1985; 24: 668
9b Blumke T, Chen Y.-H, Peng Z, Knochel P. Nat. Chem. 2010; 2: 313
9c von Zezschwitz P. Synthesis 2008; 1809

10a Starowieyski KB, Pasynkiewicz S, Skowronska-Ptasinska M. J. Organomet. Chem. 1975; 90: C43
10b Hirabayashi T, Itoh K, Sakai S, Ishii Y. J. Organomet. Chem. 1970; 25: 33
10c Basha A, Lipton M, Weinreb SM. Tetrahedron Lett. 1977; 18: 4171
10d Maruoka K, Oishi M, Yamamoto H. J. Org. Chem. 1993; 58: 7638

11a Binger P. Angew. Chem., Int. Ed. Engl. 1963; 2: 686
11b Wang B, Bonin M, Micouin L. Org. Lett. 2004; 6: 3481

12 Sasaki M, Hatta M, Tanino K, Miyashita M. Tetrahedron Lett. 2004; 45: 1911
13 Blanchet J, Bonin M, Chiaroni A, Micouin L, Riche C, Husson H.-P. Tetrahedron Lett. 1999; 40: 2935
14 Wang B, Bonin M, Micouin L. Org. Lett. 2004; 6: 3481
15 Wang B, Bonin M, Micouin L. J. Org. Chem. 2005; 70: 6126
16 Miyashita K, Tsunemi T, Hosokawa T, Ikejiri M, Imanishi T. Tetrahedron Lett. 2007; 48: 3829
17 Jackowski O, Lecourt T, Micouin L. Org. Lett. 2011; 13: 5664

18a Lee S.-H, Yoshida K, Matsushita H, Clapham B, Koch G, Zimmermann J, Janda KD. J. Org. Chem. 2004; 69: 8829
18b Matsushita H, Lee S.-H, Yoshida K, Clapham B, Koch G, Zimmermann J, Janda KD. Org. Lett. 2004; 6: 4627
18c Lee S.-H, Matsushita H, Koch G, Zimmermann J, Clapham B, Janda KD. J. Comb. Chem. 2004; 6: 822
18d Lee S.-H, Matsushita H, Clapham B, Janda KD. Tetrahedron 2004; 60: 3439
18e Matsushita H, Lee S.-H, Joung M, Clapham B, Janda KD. Tetrahedron Lett. 2004; 45: 313
18f Qi L, Meijler MM, Lee S.-H, Sun C, Janda KD. Org. Lett. 2004; 6: 1673
18g Lee S.-H, Clapham B, Koch G, Zimmermann J, Janda KD. Org. Lett. 2003; 5: 511
18h Lee S.-H, Clapham B, Koch G, Zimmermann J, Janda KD. J. Comb. Chem. 2003; 5: 188
18i Clapham B, Lee S.-H, Koch G, Zimmermann J, Janda KD. Tetrahedron Lett. 2002; 43: 5407

19 Korbad BL, Lee S.-H. Bull. Korean Chem. Soc. 2013; 34: 1266
20 General Experimental Procedure for the Synthesis of Ketone 4aa (Table 2, Entry 1) and N-H Ketimine 3aa (Table 3, Entry 1) The alane (alkynyldimethylaluminum) solution 2 was prepared according to the procedure described in ref. 11b. Alane 2a solution (1.42 mL, 1.4 M in toluene, 2.0 mmol) was added dropwise to a solution of nitrile 1a (0.103 g, 1.0 mmol) in toluene (4 mL). The resulting reaction mixture was stirred at 60 °C for 6 h, and the progress of the reaction was monitored by TLC. After cooling, the reaction was quenched by pouring of the reaction mixture into a slurry of Merck silica gel 60 (10 g, 230–400 mesh) in CHCl₃ (100 mL). After being stirred for 12 h, the resultant mixture was filtered and washed with CHCl₃. The combined filtrate was evaporated in vacuo to provide the crude residue. This was then purified by column chromatography on silica gel using EtOAc–hexanes (1:20) as eluent to provide the ketone 4aa (0.170 g, 0.85 mmol, 85%) as colorless oil. To synthesize N-H ketimine 3aa as product, the reaction was performed under the same reaction condition as described above. Then, the reaction mixture was diluted with THF (5 mL), and quenched with careful addition of a THF–H₂O mixture (5 mL, 8:2). Then the resulting mixture was stirred for 20 min, filtered through Celite, and washed with THF. The combined filtrate was evaporated to dryness to provide the crude product, which then purified by column chromatography on silica gel using EtOAc–hexanes (1:9) containing 3% Et₃N as eluent to provide the N-H ketimine 3aa (0.180 g, 0.90 mmol, 90%) as colorless oil. 1-Phenyloct-2-yn-1-one (4aa) ¹H NMR (400 MHz, CDCl₃): δ = 8.18–8.09 (m, 2 H), 7.63–7.54 (m, 1 H), 7.51–7.41 (m, 2 H), 2.49 (t, J = 7.2 Hz, 2 H), 1.68 (quint, J = 7.2 Hz, 2 H), 1.50–1.32 (m, 4 H), 0.93 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 178.5, 137.2, 134.1, 129.8, 128.7, 97.1, 79.9, 31.3, 27.7, 22.3, 19.4, 14.1. HRMS (EI⁺): m/z [M]⁺ calcd for C₁₄H₁₆O: 200.1201; found: 200.1198. 1-Phenyloct-2-yn-1-imine (3aa) ¹H NMR (400 MHz, CDCl₃): δ = 10.12 (br s, 1 H), 8.07 (s, 2 H), 7.50–7.30 (m, 3 H), 2.43 (t, J = 7.2 Hz, 2 H), 1.64 (quint, J = 7.2 Hz, 2 H), 1.45–1.27 (m, 4 H), 0.928 (t, J = 7.2 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 160.5, 136.7, 131.2, 128.2, 127.5, 95.1, 78.0, 31.0, 27.8, 22.1, 19.1, 13.9. MS (EI): m/z (%) calcd for C₁₄H₁₇N 199; found: 199 (10) [M]⁺, 198 (84), 156 (100), 143 (77), 115 (38), 77 (25).

21a Robertson GM. Imines and their N-Substituted Derivatives: NH, NR and N-Haloimines . In Comprehensive Organic Functional Group Transformations . Katritzky AR, Meth-Cohn O, Rees CW. 1st ed., Vol. 3 Elsevier Science; Oxford: 1995: 403
21b Chen G.-M, Brown HC. J. Am. Chem. Soc. 2000; 122: 4217

22a Yang X, Zhao L, Fox T, Wang Z.-X, Berke H. Angew Chem. Int. Ed. 2010; 49: 2058
22b Dejaegher Y, Mangelinckx S, De Kimpe N. Synlett 2002; 113
22c Ezhova MB, Patrick BO, James BR. Organometallics 2005; 24: 3753

23 O’Donmell MJ, Polt RL. J. Org. Chem. 1982; 47: 2663 ; and references cited therein
24 Sun Z.-M, Chen S.-P, Zhao P. Chem. Eur. J. 2010; 16: 2619
25 Laouiti A, Rammah MM, Rammah MB, Marrot J, Couty F, Evano G. Org. Lett. 2012; 14: 6
26 Dhudshia B, Tiburcio J, Thadani AN. Chem. Commun. 2005; 5551

Supplementary Material

Supporting Information