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Synlett 2015; 26(12): 1725-1731
DOI: 10.1055/s-0034-1380693
DOI: 10.1055/s-0034-1380693
letter
Bifunctional Thiourea Catalyzed Asymmetric Mannich Reaction Using Trifluoromethyl Aldimine as Trifluoromethyl Building Blocks
Further Information
Publication History
Received: 11 February 2015
Accepted after revision: 06 April 2015
Publication Date:
21 May 2015 (online)
![](https://www.thieme-connect.de/media/synlett/201512/lookinside/thumbnails/st-2015-w0095-l_10-1055_s-0034-1380693-1.jpg)
Abstract
An efficient bifunctional thiourea catalyzed asymmetric Mannich reaction with trifluoromethyl aldimine as trifluoromethyl building block was achieved to give the products in good diastereoselectivity and enantioselectivity.
Key words
thiourea catalysts - trifluoromethyl aldimine - β-keto esters - Mannich reaction - bifunctional organocatalystSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1380693.
- Supporting Information
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- 21 General Procedure for Preparing 4To the mixture of 2 (0.158 mmol, 1 equiv) and 3 (0.189 mmol, 1.2 equiv) in i-Pr2O (2 mL), DIPEA (0.237 mmol, 1.5 equiv) and thiourea catalyst 1g (9.4 mg, 10 mol%) were added successively into a flame-dried flask at 10 °C under Ar atmosphere. The mixture was stirred at 10 °C for 72 h. When the reaction was completed, the mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography using PE–EtOAc–CH2Cl2 (7:1:1) as eluent to obtain the desired product 4.Data of Compound 4a Yield 80%; white solid; mp 148–150 °C. 1H NMR (400 MHz, CDCl3): δ = 7.80–7.78 (d, J = 7.6 Hz, 1 H), 7.68–7.64 (t, J = 7.6 Hz, 1 H), 7.55–7.53 (d, J = 8.0 Hz, 1 H), 7.43–7.39 (t, J = 7.6 Hz, 1 H), 6.81 (s, 4 H), 5.23–5.15 (m, 1 H), 4.07–4.03 (d, J = 17.2 Hz, 1 H), 3.76 (s, 3 H), 3.71–3.68 (d, J = 11.6 Hz, 1 H), 3.56 (s, 3 H), 3.43–3.39 (d, J = 17.2 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.7, 167.5, 153.7, 152.3, 139.4, 135.8, 133.9, 129.4–120.9 (q, J C–F = 284.3 Hz), 128.0, 126.4, 125.1, 116.1, 114.7, 63.9, 60.9–60.1 (q, J C–F = 27.8 Hz), 55.5, 53.3, 31.4 ppm. 19F NMR (376 MHz, CDCl3): δ = –70.36 to –70.38 (d, J = 6.8 Hz) ppm. ESI-HRMS: m/z calcd for C20H18F3NO4 [M + H]+: 394.1261; found: 394.1258. IR (thin film): 3370, 3032, 2961, 1745, 1514, 1465, 1245, 1033, 828, 760 cm–1. HPLC: major ee = 84%; minor ee = 88%; dr = 80:20 [Chiralpak AD-H, n-hexane–i-PrOH (90:10), 1 mL/min, 254 nm]: t 1 (major isomer) = 17.70 min, t 2 (major isomer) = 29.28 min; t 3 (minor isomer) = 11.97 min, t 4 (minor isomer) = 22.82 min.