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Synlett 2010(18): 2725-2728  
DOI: 10.1055/s-0030-1258817
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Chiral Sodium Phosphate Catalyzed Enantioselective 1,4-Addition of TMSCN to Aromatic Enones

Jingya Yanga,b, Shaoxiang Wua, Fu-Xue Chen*a
a Department of Applied Chemistry, School of Chemical Engineering & the Environment, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, P. R. of China
Fax: +86(10)68918296; e-Mail: fuxue.chen@bit.edu.cn;
b College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, P. R. of China
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Publication History

Received 6 August 2010
Publication Date:
08 October 2010 (online)

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Chiral Sodium Phosphate Catalyzed Enantioselective 1,4-Addition of TMSCN to Aromatic EnonesSynlett 2011; 2011(05): 734-734
DOI: 10.1055/s-0030-1259697

Abstract

A facile enantioselective 1,4-addition of TMSCN to aromatic enones has been developed using chiral sodium phosphate. Thus, in the presence of 20 mol% of sodium salt generated in situ from (R)-3,3′-di(1-adamantyl)-1,1′-binaphthyl-2,2′-diylphosphoric acid and NaOH, β-cyano ketones were obtained in high yield (86-96%) and up to 72% ee within three hours at 80 ˚C in toluene.

Key words

asymmetric catalysis - enones - 1,4-addition - nitriles - phosphates

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Preparation of 6h
To a stirred solution of (R)-BINOL (6a; 1.431 g, 5.0 mmol) and 1-adamantanol (1.522 g, 10.0 mmol) in CH2Cl2 (25 mL), concd H2SO4 (0.8 mL) was added dropwise at 0 ˚C over 5 min. After stirring at 0 ˚C for 30 min the ice bath was removed. The suspension was stirred at r.t. for an additional 6 h before aq NaOH (5%) was added to neutralize H2SO4 thus to quench the reaction. The resulting mixture was extracted by CH2Cl2 twice. The combined organic phase was washed with brine, dried over Na2SO4, and concentrated. The crude solid was purified by silica gel chromatography using PE-EtOAc (10:1, v/v) as the eluent to yield (R)-3,3′-di(1-adamantyl)-1,1′-binaphthyl-2,2′-diol (6h) as a white solid (1.670 g, 3.01 mmol); 60% yield, mp 207-209 ˚C; [α]D ¹7 -82.5 (c 0.114, CHCl3). ¹H NMR (500 MHz, CDCl3): δ = 1.79-1.85 (dd, J = 21.0, 12.0 Hz, 12 H, CHCH 2CH), 2.00 (s, 12 H, CCH 2CH), 2.15 [s, 6 H, CH(CH2)3], 7.17 (d, J = 9.0 Hz, 2 H, ArH), 7.37-7.43 (m, 4 H, ArH), 7.80 (s, 2 H, ArH), 7.97 (d, J = 9.0 Hz, 2 H, ArH) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 29.0, 36.1, 36.8, 43.1, 110.7, 117.5, 123.5, 124.0, 125.7, 129.5, 131.4, 131.6, 147.0, 152.3 ppm.
Preparation of 7h
(R)-3,3′-Di(1-adamantyl)-1,1′-binaphthyl-2,2′-diol (6h; 555 mg, 1 mmol) was dissolved in pyridine (3 mL) in a 50 mL Schlenk tube. Phosphorous oxychloride (185 µL, 2 mmol) was added dropwise at r.t. After stirring for 10 h at r.t., H2O (3 mL) was added. The resulting mixture was stirred for additional 6 h at r.t. followed by addition of CH2Cl2. All pyridine was removed by reverse extraction with 1 M HCl. The organic phase was washed with brine, dried over Na2SO4, and concentrated. The crude solid was purified by flash silica gel chromatography CH2Cl2-MeOH (5:1, v/v) as the eluent to yield (R)-3,3′-di(1-adamantyl)-1,1′-binaphthyl-2,2′-diylphosphoric acid (7h) as a white solid (555 mg, 0.9 mmol); 90% yield; mp >300 ˚C; [α]D ²¹ -283.3 (c 0.240, CHCl3). ¹H NMR (400 MHz, DMSO-d 6): δ = 1.75 (s, 12 H, CHCH 2CH), 1.95 (s, 12 H, CCH 2CH), 2.07 [s, 6 H, CH(CH2)3], 7.21-7.23 (m, 2 H, ArH), 7.41-7.42 (m, 4 H, ArH), 7.87 (s, 2 H, ArH), 8.01 (d, J = 8.8 Hz, 2 H, ArH) ppm. ¹³C NMR (100 MHz, DMSO-d 6): δ = 28.5, 35.9, 36.4, 42.7, 121.6, 122.4, 123.4, 124.3, 126.0, 130.0, 130.3, 130.8, 147.1, 149.3 ppm. ³¹P NMR (162 MHz, DMSO-d 6): δ = 3.5 (s) ppm.

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Typical Procedure for the Asymmetric 1,4-Addition of TMSCN to Enones After (R)-3,3′-di(1-adamantyl)-1,1′-binaphthyl-2,2′-diyl phosphoric acid (7h, 18.5 mg, 0.03 mmol, 20 mol%) and NaOH (1.2 mg, 0.03 mmol, 20 mol%) were placed in a dry Schlenk tube under argon. Toluene (0.5 mL) was added, and the mixture was stirred at 30 ˚C for 1 h. Then, chalcone (1a, 31.2 mg, 0.15 mmol), 2-t-BuPhOH (0.03 mmol, 20 mol%), additional toluene (0.5 mL), and TMSCN (0.33 mmol, 2.2 equiv) were added at r.t. Equipped with cold finger, the reaction mixture was stirred at 80 ˚C until the reaction was completed (monitored by TLC). The reaction was quenched with 1 M HCl (0.3 mL) followed by diluting with dioxane (2 mL) and stirring for additional 30 min at r.t. To work it up, H2O (2 mL) was added, and the resulting mixture was extracted with EtOAc (5 mL) (Caution! HCN possibly generated in the reaction mixture is highly toxic. Those operations should be conducted in a well-ventilated hood). The extract was washed with H2O (2 mL), brine (3 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (PE-EtOAc, 20:1, v/v) to afford pure product 2a as a white solid in 94% yield and 71% ee.
4-Oxo-2,4-diphenylbutanenitrile (2a)
¹H NMR (400 MHz, CDCl3): δ = 3.52 (dd, J = 18.0, 6.0 Hz, 1 H, NCCHCH A HBCO), 3.74 (dd, J = 18.0, 8.0 Hz, 1 H, NCCHCHA H B CO), 4.57 (dd, J = 8.0, 6.0 Hz, 1 H, NCCHCHAHBCO), 7.34-7.49 (m, 7 H, ArH), 7.58-7.62 (m, 1 H, ArH), 7.92-7.94 (m, 2 H, ArH) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 31.9, 44.5, 120.6, 127.5, 128.1, 128.4, 128.8, 129.3, 133.9, 135.3, 135.8, 194.6 ppm. IR (KBr): ν = 1681, 2236 cm-¹. HPLC [Chiralpak AS-H, 254 nm, n-hexane-2-PrOH (70:30), 1.0 mL/min]: t R(major) = 13.3 min, t R(minor) = 21.4 min; [α]D ¹7 -20.0 (c 0.100, CH2Cl2, 71% ee).

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CCDC-787260 contains the supplementary crystallographic data of 2f for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.