Direct Synthesis of β,γ-Unsaturated α-Keto Esters from Aldehydes and Pyruvates

John Kamanda Mansaray; Jiarui Sun; Shisheng Huang; Weijun Yao

doi:10.1055/s-0037-1612255

Synlett, Table of Contents

Synlett 2019; 30(07): 809-812
DOI: 10.1055/s-0037-1612255

letter

Direct Synthesis of β,γ-Unsaturated α-Keto Esters from Aldehydes and Pyruvates

John Kamanda Mansaray

,

Jiarui Sun

,

Shisheng Huang

,

Weijun Yao *

Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China Email: orgywj@zstu.edu.cn

› Author Affiliations

Abstract

All articles of this category

Abstract

Herein, we describe two practical methods to synthesize β,γ-unsaturated α-keto esters directly from aldehydes and pyruvates promoted by BF₃•Et₂O in the presence of Ac₂O or by Ti(OEt)₄ under mild conditions. A variety of aromatic aldehydes was tolerated to afford the desired products in moderate to excellent yield. Moreover, aliphatic aldehydes and Isatin were also employed to give the γ-alkyl β,γ-unsaturated α-keto esters in moderate yield with use of the Ti(OEt)₄ system.

Key words

unsaturated α-keto esters - step economy - pyruvates - aldehydes - aldol condensation

Full Text

References

References and Notes

For reviews see:

1a Desimoni G, Faita G, Quadrell P. Chem. Rev. 2013; 113: 5924-5988
1b Eftekhari-Sis B, Zirak M. Chem. Rev. 2015; 115: 151-264

2 Dou X, Hayashi T. Adv. Synth. Catal. 2016; 358: 1054-1058

3a Zhang Q, Lv J, Li S, Luo S. Org. Lett. 2018; 20: 2269-2272
3b Ouyang B, Yu T, Luo R, Lu G. Org. Biomol. Chem. 2014; 12: 4172-4176

4a Sinha D, Perera S, Zhao JC.-G. Chem. Eur. J. 2013; 19: 6976-6979
4b Lv J, Zhang L, Luo S, Cheng J.-P. Angew. Chem. Int. Ed. 2013; 52: 9786-9790
4c Wang L, Lv J, Zhang L, Luo S. Angew. Chem. Int. Ed. 2017; 56: 10867-10871
4d Kano T, Maruyama H, Hommaa C, Maruoka K. Chem. Commun. 2018; 54: 3496-3499
4e Liu Q.-J, Wang L, Kang Q.-K, Zhang XP, Tang Y. Angew. Chem. Int. Ed. 2016; 55: 9220-9223

5a Hao X, Lin L, Tan F, Ge S, Liu X, Feng X. Org. Chem. Front. 2017; 4: 1647-1650
5b Zhang Y, Yang N, Liu X, Guo J, Zhang X, Lin L, Hua C, Feng X. Chem. Commun. 2015; 51: 8432-8435
5c Chen X, Jiang H, Hou B, Gong W, Liu Y, Cui Y. J. Am. Chem. Soc. 2017; 139: 13476-13482

6a Li Y, Huang Y, Gui Y, Sun J, Li J, Zha Z, Wang Z. Org. Lett. 2017; 19: 6416-6419
6b Deng Y.-H, Chen J.-Q, He L, Kang T. -R, Liu Q.-Z, Luo S.-W, Yuan W.-C. Chem. Eur. J. 2013; 19: 7143-7150
6c Konda S, Guo Q.-S, Abe M, Huang H, Arman H, Zhao JC.-G. J. Org. Chem. 2015; 80: 806-815
6d Wei A.-J, Nie J, Zheng Y, Ma J.-A. J. Org. Chem. 2015; 80: 3766-3776

7a Kuang Y, Shen B, Dai L, Yao Q, Liu X, Lin L, Feng X. Chem. Sci. 2018; 9: 688-692
7b Konda S, Zhao JC.-G. Tetrahedron Lett. 2014; 55: 5216-5218
7c Chew R, Teo K, Huang Y, Li B.-B, Li Y, Pullarkat SA, Leung P.-H. Chem. Commun. 2014; 50: 8768-8770
7d Chen S, Wang Y, Zhou Z. J. Org. Chem. 2016; 81: 11432-11438

8a Zhu C, Bi B, Ding Y, Zhang T, Chen Q.-Y. Org. Biomol. Chem. 2015; 13: 6278-6285
8b Jiang L, Jin W, Hu W. ACS Catal. 2016; 6: 6146-6150

9a Yao Q, Yu H, Zhang H, Dong S, Chang F, Lin L, Liu X, Feng X. Chem. Commun. 2018; 54: 3375-3378
9b Jin H, Lee J, Shi H, Lee J, Yoo E, Song C, Ryu D. Org. Lett. 2018; 20: 1584-1588
9c Sadeghzadeh S. RSC. Adv. 2016; 6: 99586-99594
9d Cheng Y, Han Y, Li P. Org. Lett. 2017; 19: 4774-4777
9e Wang S, Radosevich AT. Org. Lett. 2013; 15: 1926-1929
9f Li E, Huang Y. Chem. Eur. J. 2014; 20: 3520-3527
9g Duan J, Cao F, Wang X, Ma C. Chem. Commun. 2013; 49: 1124-1126

10 Stecher ED, Ryder HF. J. Am. Chem. Soc. 1952; 74: 4392-4395
11 Sugimura H, Yoshida K. Bull. Chem. Soc. Jpn. 1992; 65: 3209-3211
12 Meijer LH, Pandit UK. Tetrahedron 1985; 41: 467-472
13 Trost BM. Angew. Chem., Int. Ed. Engl. 1995; 34: 259-281
14 Wender PA, Verma VA, Paxton TJ, Pillow TH. Acc. Chem. Res. 2008; 41: 40-49
15 Dujardin G, Leconte S, Bénard A, Brown E. Synlett 2001; 147-149

16a Yao W, Dou X, Lu Y. J. Am. Chem. Soc. 2015; 137: 54-57
16b Yao W, Pan L, Wu Y, Ma C. Org. Lett. 2010; 12: 2422-2425
16c Yao W, Wu Y, Wang G, Zhang Y, Ma C. Angew. Chem. Int. Ed. 2009; 48: 9713-9716

17 β,γ-Unsaturated α-Keto Esters (1a–u); General Procedure A To the solution of aldehyde (2 mmol) and pyruvate (2.4 mmol) in toluene (10 mL) were added BF₃•Et₂O (1 mmol) and Ac₂O (3 mmol). After stirring for 48 h at 40 °C, the mixture was poured into saturated NaHCO₃ (aq) solution (20 mL). The separated aqueous phase was extracted with ethyl acetate (20 mL) and the combined organic phases were washed by brine (20 mL), dried with Na₂SO₄, filtered, and concentrated in vacuum. The residue was filtered through a short pad of silica gel with petroleum ether/ethyl acetate (10:1) as the eluent to obtain a crude product, which was analyzed by ¹H NMR spectroscopy to calculate the E/Z ratio. Further purification was carried out by column chromatography on silica gel with petroleum ether/ethyl acetate (20:1) as the eluent to afford the products 1. Ethyl (E)-4-Cyclohexyl-2-oxobut-3-enoate (1t) Pale yellow oil; yield: 176 mg (42%). ¹H NMR spectrum of the crude product shows an E/Z ratio of >19:1. ¹H NMR (400 MHz CDCl₃): δ = 7.09 (dd, J = 16.0, 6.8 Hz, 1 H), 6.57 (dd, J = 16.0, 1.1 Hz, 1 H), 4.31 (q, J = 7.1 Hz, 2 H), 2.29–2.13 (m, 1 H), 1.78–1.64 (m, 5 H), 1.35 (t, J = 7.1 Hz, 3 H), 1.31–1.08 (m, 5 H). ¹³C NMR (101 MHz, CDCl₃): δ = 183.8, 162.5, 159.6, 122.7, 62.2, 41.2, 31.4, 25.8, 25.6, 14.0.
18 Collados JF, Toledano E, Guijarro D, Yus M. J. Org. Chem. 2012; 77: 5744-5750
19 Ti(OEt)₄ System; General Procedure B To the solution of aldehyde (2 mmol) and pyruvate (2.4 mmol) in toluene (10 mL) was added Ti(OEt)₄ (2.4 mmol). After stirring for 72 h at 40 °C, the mixture was diluted with ethyl acetate (40 mL) and quenched with water (1 mL). After stirring for 0.5 h at rt, the mixture was dried with Na₂SO₄, filtered, and concentrated in vacuum. The residue was filtered through a short pad of silica gel with petroleum ether/ethyl acetate (10:1) as the eluent to obtain a crude product, which was analyzed by ¹H NMR spectroscopy to calculate the E/Z ratio. Further purification was carried out by column chromatography on silica gel with petroleum ether/ethyl acetate (20:1) as the eluent to afford the products 1. Ethyl (E)-2-Oxohept-3-enoate (1s) Pale yellow oil; yield: 122 mg (36%). ¹H NMR spectrum of the crude product shows an E/Z ratio of >19:1. ¹H NMR (400 MHz, CDCl₃): δ = 7.18 (dt, J = 15.8, 6.9 Hz, 1 H), 6.64 (d, J = 15.9 Hz, 1 H), 6.64 (d, J = 15.9 Hz, 1 H), 4.34 (q, J = 7.1 Hz, 2 H), 2.29 (td, J = 8.0, 1.0 Hz, 2 H), 1.59–1.47 (m, 2 H), 1.37 (t, J = 7.1 Hz, 3 H), 0.95 (t, J = 7.4 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 183.5, 162.4, 154.9, 125.3, 62.30, 35.1, 21.1, 14.0, 13.7.
20 Yang C, Chen X, Tang T, He Z. Org. Lett. 2016; 18: 1486-1489

Supplementary Material

Supporting Information