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

Atanu Ghoshal; Asit R. Sarkar; Govindaswamy Manickam; R. Senthil Kumaran; J. Jayashankaran

doi:10.1055/s-0029-1219949

LETTER

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

Atanu Ghoshal^a,b, Asit R. Sarkar^a, Govindaswamy Manickam^b, R. Senthil Kumaran^b, 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;

Abstract

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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

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References

References and Notes

<A NAME="RD02310ST-1A">1a</A> Kagan HB. Asymmetric Synthesis Vol. 5: Academic Press; New York: 1985. p.1-39

<A NAME="RD02310ST-1B">1b</A> Brunner H. Topics in Stereochemistry Vol. 18: Interscience; New York: 1988. p.129-247

<A NAME="RD02310ST-2A">2a</A> Noyori R. Ohkuma T. Kitamura M. Takaya H. Sayo N. Kumobayashi H. Akutagawa S. J. Am. Chem. Soc. 1987, 109: 5856

<A NAME="RD02310ST-2B">2b</A> Corey EJ. Bakshi RK. Shibata S. Chen C.-P. Singh VK. J. Am. Chem. Soc. 1987, 109: 7925

<A NAME="RD02310ST-3">3</A> Bolm C. Angew. Chem., Int. Ed. Engl. 1991, 30: 542

<A NAME="RD02310ST-4A">4a</A> Nishiyama H. Sakaguchi H. Nakamura T. Horihata M. Kondo M. Itoh K. Organometallics 1989, 8: 846

<A NAME="RD02310ST-4B">4b</A> Nishiyama H. Kondo M. Nakamura T. Itoh K. Organometallics 1991, 10: 500

<A NAME="RD02310ST-4C">4c</A> Nishiyama H. Yamaguchi S. Kondo M. Itoh K. J. Org. Chem. 1992, 57: 4306

<A NAME="RD02310ST-4D">4d</A> Nishiyama H. Park S.-B. Itoh K. Tetrahedron: Asymmetry 1992, 3: 1029

<A NAME="RD02310ST-4E">4e</A> Nishiyama H. Yamaguchi S. Park S.-B. Itoh K. Tetrahedron: Asymmetry 1993, 4: 143

<A NAME="RD02310ST-5A">5a</A> Peyronal JF. Kagan HB. Nouv. J. Chim. 1978, 2: 211

<A NAME="RD02310ST-5B">5b</A> Ojima I. Kogure T. Kumagai M. J. Org. Chem. 1977, 42: 1671

<A NAME="RD02310ST-5C">5c</A> Brunner H. Obermann U. Chem. Ber. 1989, 122: 499

<A NAME="RD02310ST-5D">5d</A> Brunner H. Brandl P. Tetrahedron: Asymmetry 1991, 2: 919

<A NAME="RD02310ST-5E">5e</A> Gladiali S. Pinna L. Delogu DG. Graf E. Brunner H. Tetrahedron: Asymmetry 1990, 1: 937

<A NAME="RD02310ST-6">6</A> Jacobsen EN. Zhang W. Güler ML. J. Am. Chem. Soc. 1991, 113: 6703

<A NAME="RD02310ST-7A">7a</A> Van Staveren CJ. Aarts VMLJ. Grootenhuis PDJ. Droppers WJH. Van Eerden J. Harkema S. Reinhoudt DN. J. Am. Chem. Soc. 1988, 110: 8134

<A NAME="RD02310ST-7B">7b</A> Hong F. Hollenback D. Singer JW. Klein P. Bioorg. Med. Chem. Lett. 2005, 15: 4703

<A NAME="RD02310ST-8A">8a</A> Belanger DB, Siddiqui MA, Curran PJ, Hamman B, Zhao L, Reddy PAP, Tadikonda PK, Shipps GW, and Mansoor UF. inventors; WO 082487 A2.

<A NAME="RD02310ST-8B">8b</A> Oh-e T. Miyaura N. Suzuki A. J. Org. Chem. 1993, 58: 2201

<A NAME="RD02310ST-8C">8c</A> Miyaura N. Suzuki A. Chem. Rev. 1995, 95: 2457

<A NAME="RD02310ST-8D">8d</A> Stanforth SP. Tetrahedron 1998, 54: 263

<A NAME="RD02310ST-8E">8e</A> Sutton AE. Clardy J. Tetrahedron Lett. 2001, 42: 547

<A NAME="RD02310ST-8F">8f</A> Hovinen J, Mukkala VM, Hakala H, and Peu-Rahlati J. inventors; WO 058877 A1.

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.

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.

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.

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.

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

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.