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

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.

Key words

PyBOX - asymmetric hydrosilylation - rhodium catalyst - enantioselectivity - electronic effect

References and Notes

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• 1b Brunner H. Topics in Stereochemistry   Vol. 18:  Interscience; New York: 1988.  p.129-247  
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• 4b Nishiyama H. Kondo M. Nakamura T. Itoh K. Organometallics  1991,  10:  500 
• 4c Nishiyama H. Yamaguchi S. Kondo M. Itoh K. J. Org. Chem.  1992,  57:  4306 
• 4d Nishiyama H. Park S.-B. Itoh K. Tetrahedron: Asymmetry  1992,  3:  1029 
• 4e Nishiyama H. Yamaguchi S. Park S.-B. Itoh K. Tetrahedron: Asymmetry  1993,  4:  143 
• 5a Peyronal JF. Kagan HB. Nouv. J. Chim.  1978,  2:  211 
• 5b Ojima I. Kogure T. Kumagai M. J. Org. Chem.  1977,  42:  1671 
• 5c Brunner H. Obermann U. Chem. Ber.  1989,  122:  499 
• 5d Brunner H. Brandl P. Tetrahedron: Asymmetry  1991,  2:  919 
• 5e Gladiali S. Pinna L. Delogu DG. Graf E. Brunner H. Tetrahedron: Asymmetry  1990,  1:  937 
• 6 Jacobsen EN. Zhang W. Güler ML. J. Am. Chem. Soc.  1991,  113:  6703 
• 7a Van Staveren CJ. Aarts VMLJ. Grootenhuis PDJ. Droppers WJH. Van Eerden J. Harkema S. Reinhoudt DN. J. Am. Chem. Soc.  1988,  110:  8134 
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• 8a Belanger DB, Siddiqui MA, Curran PJ, Hamman B, Zhao L, Reddy PAP, Tadikonda PK, Shipps GW, and Mansoor UF. inventors; WO 082487  A2. 
• 8b Oh-e T. Miyaura N. Suzuki A. J. Org. Chem.  1993,  58:  2201 
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• 8d Stanforth SP. Tetrahedron  1998,  54:  263 
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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.