Synlett 2010(10): 1459-1462  
DOI: 10.1055/s-0029-1219949
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Rhodium-Catalyzed Asymmetric Hydrosilylation of Ketones Employing a New Ligand Embodying the Bis(oxazolinyl)pyridine Moiety

Atanu Ghoshala,b, Asit R. Sarkara, Govindaswamy Manickamb, R. Senthil Kumaranb, J. Jayashankaran*b
a Department of Chemistry, University of Kalyani, Kalyani 741235, India
b Syngene International Ltd., Biocon Park, Plot Nos. 2 & 3, Bommasandra-Jigani Road, Bangalore 560099, India
Fax: +91(33)25828282; e-Mail: jjayash@gmail.com;
Further Information

Publication History

Received 25 January 2010
Publication Date:
25 May 2010 (online)

Abstract

A general approach to new ligands embodying bis(oxazolinyl)pyridine has been developed, employing palladium-catalyzed Suzuki coupling and base-mediated cyclization as pivotal steps. A rhodium catalyst derived from the ligand 4-(4-ethylphenyl)-2,6-bis(4-isopropyl-4,5-dihydrooxazol-2-yl)pyridine gave excellent enantioselectivity in the asymmetric hydrosilylation of ketones. In addition the electronic effect of remote substituents on the catalytic activity of rhodium catalyst was studied.

    References and Notes

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9

The overall yield of the ligand 5a is 45%. Similarly the overall yields for ligands 5b,c,d,e,f are 39%, 40%, 38%, 33%, and 28%, respectively.

10

All compounds were characterized based on ¹H NMR and mass spectrometric analysis. Enantiomeric excesses of alcohols were determined by chiral HPLC using either Chiracel or Chiralpak OD-H columns.

11

4-(4-Ethylphenyl)-2,6-bis(4-isopropyl-4,5-dihydro-oxazol-2-yl)pyridine (5d)White solid. [α]D ²² -44.7 (c 1.0, CHCl3). ¹H NMR (400 MHz, CDCl3): δ = 8.44 (s, 2 H), 7.72 (dd, J = 1.7, 6.5 Hz, 2 H), 7.33 (d, J = 8.2 Hz, 2 H), 4.57 (d, J = 8.3 Hz, 1 H), 4.55 (d, J = 8.3 Hz, 1 H), 4.28 (d, J = 8.4 Hz, 1 H), 4.24 (d, J = 8.3 Hz, 1 H), 4.15-4.21 (m, 2 H), 2.72 (q, J = 7.6 Hz, 2 H), 1.90 (q, J = 6.6 Hz, 2 H), 1.28 (t, J = 7.6 Hz, 3 H), 1.07 (d, J = 6.7 Hz, 6 H), 0.96 (d, J = 6.7 Hz, 6 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 162.5, 149.8, 147.4, 146.2, 134.0, 128.7, 127.2, 123.2, 72.9, 70.9, 32.9, 29.7, 28.6, 19.1, 18.3, 15.4 ppm. HRMS: m/z calcd for C25H31N3O2: 405.2416; found: 405.2437.

12

Compound 6dOrange solid. ¹H NMR (400 MHz, CDCl3): δ = 8.12 (s, 2 H), 7.63 (d, J = 7.8 Hz, 2 H), 7.44 (d, J = 7.7 Hz, 2 H), 4.92-5.03 (m, 4 H), 4.69 (d, J = 7.3 Hz, 2 H), 3.09 (m, 2 H), 2.78 (q, J = 7.6 Hz, 2 H), 1.31 (t, J = 7.6 Hz, 3 H), 1.03 (d, J = 6.6 Hz, 6 H), 1.0 (d, J = 7.1 Hz, 6 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 166.2, 153.9, 148.8, 146.9, 132.2, 129.6, 127.5, 123.9, 73.2, 68.7, 29.7, 28.7, 28.4, 19.6, 15.2, 15.1 ppm.

13

Catalyst 6 was activated by AgBF4 followed by treatment with Ph2SiH2 to form an intermediate complex. The Rh-Si bond of the complex preferably attacks the re face of the ketone to obtain the S-alcohol

14

Typical Procedure for the Asymmetric Hydrosilylation of Acetophenone 8: ( S )-1-Phenylethanol 9A suspension of the catalyst 6d (0.0333 mmol) and AgBF4 (0.0333 mmol) in THF (2 mL) was stirred at 10 ˚C for 1 h, and acetophenone 8 (0.3329 mmol) was added to the reaction mixture at the same temperature. Diphenylsilane (0.5332 mmol) was added at 0 ˚C and the mixture allowed to warm up to 10 ˚C and stirred for a further 20 h. The reaction was quenched with MeOH (2 mL) followed by the addition of 1.5 M HCl (2 mL). The mixture was extracted with EtOAc (3 × 5 mL), and the combined organic layers were washed with H2O (5 mL), brine (5 mL), dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel column chromatography using 10% EtOAc in hexane to obtain 9 (92%). ¹H NMR (400 MHz, CDCl3): δ = 7.28-7.40 (m, 5 H), 4.93 (q, J = 6.4 Hz, 1 H), 1.52 (d, J = 6.4 Hz, 3 H). The ee was determined by HPLC with Chiracel OD-H column, 5% EtOH-hexanes, 0.7 mL/min, 210-400 nm; t R(major) = 11.7 (98.8%), t R(minor) = 10.1 (1.1%), 98% ee.