Enantioselective Radical Reactions: Formation of Chiral Quaternary Centers

Mukund P. Sibi; Liwen He

doi:10.1055/s-2006-933116

LETTER

Enantioselective Radical Reactions: Formation of Chiral Quaternary Centers

Mukund P. Sibi*, Liwen He
Department of Chemistry, North Dakota State University, Fargo, ND 58105, USA
Fax: +1(701)2311057; e-Mail: Mukund.Sibi@ndsu.edu;

Abstract

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Abstract

A novel addition/trapping radical reaction to establish all-carbon chiral quaternary centers has been developed.

Key words

radical reactions - chiral Lewis acid - quaternary centers - conjugate additions - imides

Full Text

References

References and Notes

For reviews on quaternary centers see:

<A NAME="RS11305ST-1A">1a</A> Denissova I. Barriault L. Tetrahedron 2003, 59: 10105

<A NAME="RS11305ST-1B">1b</A> Christoffers J. Baro A. Angew. Chem. Int. Ed. 2003, 42: 1688

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<A NAME="RS11305ST-1D">1d</A> Corey EJ. Guzman-Perez A. Angew. Chem. Int. Ed. 1998, 37: 388

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<A NAME="RS11305ST-2">2</A> Radicals in Organic Synthesis Vol. 1 and 2: Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.

<A NAME="RS11305ST-3">3</A> For a recent review see: Patil K. Sibi MP. In Quaternary Stereocenters - Challenges for Organic Synthesis Christoffers J., Baro A., Wiley-VCH; Weinheim: 2005. p.287-313

<A NAME="RS11305ST-4A">4a</A> Sibi MP. Manyem S. Zimmerman J. Chem. Rev. 2003, 103: 3263

<A NAME="RS11305ST-4B">4b</A> Sibi MP. Porter NA. Acc. Chem. Res. 1999, 33: 163

<A NAME="RS11305ST-4C">4c</A> Sibi MP. Manyem S. Tetrahedron 2000, 56: 8033

<A NAME="RS11305ST-4D">4d</A> Parsons AF. Bar S. Chem. Soc. Rev. 2003, 251

<A NAME="RS11305ST-5A">5a</A> Murakata M. Jono T. Mizuno Y. Hoshino O. J. Am. Chem. Soc. 1997, 119: 11713

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<A NAME="RS11305ST-6A">6a</A> Yang D. Gu S. Yan YL. Zhu NY. Cheung KK. J. Am. Chem. Soc. 2001, 123: 8612

<A NAME="RS11305ST-6B">6b</A> Yang D. Gu S. Yan YL. Zhao HW. Zhu NY. Angew. Chem. Int. Ed. 2002, 41: 3014

Also see:

<A NAME="RS11305ST-6C">6c</A> Yang D. Gao Q. Lee O.-Y. Org. Lett. 2002, 4: 1239

<A NAME="RS11305ST-6D">6d</A> Lin H.-H. Chang W.-S. Luo S.-Y. Sha C.-K. Org. Lett. 2004, 6: 3289

<A NAME="RS11305ST-6E">6e</A> Yang D. Yan Y.-L. Law K.-L. Zhu N.-Y. Tetrahedron 2003, 59: 10465

<A NAME="RS11305ST-6F">6f</A> Yang D. Ye X.-Y. Gu S. Xu M. J. Am. Chem. Soc. 1999, 121: 5579

<A NAME="RS11305ST-6G">6g</A> Yang D. Ye X.-Y. Xu M. J. Org. Chem. 2000, 65: 2208

<A NAME="RS11305ST-6H">6h</A> For formation of quaternary center by radical combination see: Ellison ME. Ng D. Dang H. Garcia-Garibay MA. Org. Lett. 2003, 5: 2531

<A NAME="RS11305ST-7A">7a</A> Imide: Sibi MP. Petrovic G. Zimmerman J. J. Am. Chem. Soc. 2005, 127: 2390

<A NAME="RS11305ST-7B">7b</A> Sultam: Sibi MP. Sausker JB. J. Am. Chem. Soc. 2002, 124: 984

<A NAME="RS11305ST-7C">7c</A> Oxazolidinones: Sibi MP. Ji J. Wu JH. Gurtler S. Porter NA. J. Am. Chem. Soc. 1996, 118: 9800

<A NAME="RS11305ST-7D">7d</A> Pyrrolidinones: Sibi MP. He L. Org. Lett. 2004, 6: 1749

<A NAME="RS11305ST-7E">7e</A> Chiral relay templates: Sibi MP. Prabagaran N. Synlett 2004, 2421

<A NAME="RS11305ST-7F">7f</A> Pyrazoles: Sibi MP. Shay JJ. Ji J. Tetrahedron Lett. 1997, 38: 5955

<A NAME="RS11305ST-8A">8a</A> Sibi MP. Prabagaran N. Ghorpade SG. Jasperse CP. J. Am. Chem. Soc. 2003, 125: 11796

<A NAME="RS11305ST-8B">8b</A> Sibi MP. Petrovic G. Zimmerman J. J. Am. Chem. Soc. 2005, 127: 2390

<A NAME="RS11305ST-8C">8c</A> For the use of imide templates in conjugate additions see: Sammis GM. Jacobsen EN. J. Am. Chem. Soc. 2003, 125: 4442 ; and references cited therein.

<A NAME="RS11305ST-9A">9a</A> For addition/trapping experiments from our laboratory, see: Sibi MP. Ji J. J. Org. Chem. 1996, 61: 6090

<A NAME="RS11305ST-9B">9b</A> Sibi MP. Chen J. J. Am. Chem. Soc. 2001, 123: 9472

<A NAME="RS11305ST-9C">9c</A> Sibi MP. Manyem S. Subramaniam R. Tetrahedron 2003, 59: 10575

For examples of radical reactions where stereocenter α to a carbonyl is established, see:

<A NAME="RS11305ST-10A">10a</A> Stereochemistry of Radical Reactions Curran DP. Porter NA. Giese B. VCH; Weinheim: 1995.

<A NAME="RS11305ST-10B">10b</A> Durkin K. Liotta D. Rancourt J. Lavallée J.-F. Boisvert L. Guindon Y. J. Am. Chem. Soc. 1992, 114: 4912

<A NAME="RS11305ST-10C">10c</A> Guindon Y. Houde K. Prevost M. Cardinal-David B. Landry SR. Daoust B. Bencheqroun M. Guerin B. J. Am. Chem. Soc. 2001, 123: 8496

<A NAME="RS11305ST-10D">10d</A> Curran DP. Abraham AC. Tetrahedron 1993, 49: 4821

<A NAME="RS11305ST-10E">10e</A> Curran DP. Ramamoorthy PS. Tetrahedron 1993, 49: 4841

<A NAME="RS11305ST-10F">10f</A> Curran DP. Geib S. De Mello N. Tetrahedron 1999, 55: 5681

For a reaction with tiglates see:

<A NAME="RS11305ST-10G">10g</A> Kopping B. Chatgilialoglu C. Zehnder M. Giese B. J. Org. Chem. 1992, 57: 3994

<A NAME="RS11305ST-10H">10h</A> Watanabe Y. Mase N. Furue R. Toru T. Tetrahedron Lett. 2001, 42: 2981

<A NAME="RS11305ST-10I">10i</A> Wu JH. Zhang G. Porter NA. Tetrahedron Lett. 1997, 38: 2067

<A NAME="RS11305ST-10J">10j</A> Wu JH. Radinov R. Porter NA. J. Am. Chem. Soc. 1995, 117: 11029

The ethyl addition products were formed in minor amounts depending on the chiral Lewis acid and/or template employed for the reaction.

<A NAME="RS11305ST-12A">12a</A> Kanemasa S. Oderaotoshi Y. Yamamoto H. Tanaka J. Wada E. Curran DP. J. Org. Chem. 1997, 62: 6454

<A NAME="RS11305ST-12B">12b</A> Iserloh U. Curran DP. Kanemasa S. Tetrahedron: Asymmetry 1999, 10: 2417

<A NAME="RS11305ST-12C">12c</A> Iserloh U. Oderaotoshi Y. Kanemasa S. Curran DP. Org. Synth. 2003, 80: 46

<A NAME="RS11305ST-13A">13a</A> Sibi MP. Ji J. J. Org. Chem. 1997, 62: 3800

<A NAME="RS11305ST-13B">13b</A> Sibi MP. Shay JJ. Liu M. Jasperse CP. J. Am. Chem. Soc. 1998, 120: 6615

<A NAME="RS11305ST-13C">13c</A> Sibi MP. Ma Z. Jasperse CP. J. Am. Chem. Soc. 2005, 127: 5764

<A NAME="RS11305ST-13D">13d</A> Sibi MP. Itoh K. Jasperse CP. J. Am. Chem. Soc. 2004, 126: 5366

<A NAME="RS11305ST-13E">13e</A> Sibi MP. Stanley LM. Jasperse CP. J. Am. Chem. Soc. 2005, 127: 8276

General Procedure for the Addition/Trapping Reaction
To a suspension of Lewis acid (0.2 mmol) in 1.5 mL of CH₂Cl₂ was added the chiral ligand (0.2 mmol) and stirred at r.t. for 2 h resulting in a clear solution. Substrate (0.2 mmol) in CH₂Cl₂ was added to above chiral Lewis acid and the reaction cooled to -78 °C and stirred for 1 h. The radical precursor (6 mmol) was added, followed by addition of allyltributyltin (0.62 mL, 2 mmol), Et₃B (1 mL, 1 mmol) and 10 mL of O₂. The reaction was allowed to reach r.t. over 12 h. The reaction mixture was diluted with CH₂Cl₂ (20 mL) and silica gel (4 g) was added. After removal of the solvent, the silica gel was washed with hexane (30 mL), followed by hexane-EtOAc (1:1, 30 mL). The hexane-EtOAc solution was concentrated to give the crude, which was purified by flash chromatography to give pure product. The enantio-meric purity was determined by chiral GC. Conditions for GC analyses: Supelco β-Dex 225 column, 30 m in length, 0.25 mm inner diameter, isotherm temperature program, and He as carrier gas (1 mL/min).
2-Isobutyl-2-methylpent-4-enoic Acid (2,2-Dimethyl-propionyl)amide (4)
Mp 67-68 °C; R _f = 0.3 (hexane-EtOAc, 4:1); 70% ee (1 mL/min, T = 80 °C, t _R1 = 42 min, t _R2 = 43.6 min). IR (film): 1758, 1478, 1453 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 8.25 (br s, 1 H), 5.76 (m, 1 H), 5.15-5.10 (m, 2 H), 2.39 (dd, J = 14.0, 7.0 Hz, 1 H), 2.18 (dd, J = 14.5, 7.5 Hz, 1 H), 1.72 (m, 1 H), 1.62 (dd, J = 14.5, 7.0 Hz, 1 H), 1.41 (dd, J = 14.5, 5.5 Hz, 1 H), 1.24 (s, 9 H), 1.21 (s, 3 H), 0.92 (d, J = 6.5 Hz, 3 H), 0.87 (d, J = 6.5 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 175.0, 174.3, 133.1, 119.3, 48.5, 47.5, 44.7, 40.5, 27.1, 24.7, 24.5, 23.5, 21.3. HRMS: m/z calcd for C₁₅H₂₇NO₂Na⁺: 276.1933; found: 276.1932.
2-(2,2-Dimethylpropyl)-2-methylpent-4-enoic Acid (2,2-Dimethylpropionyl)amide (18)
Mp 73-74 °C; R _f = 0.33 (hexane-EtOAc, 4:1); 73% ee (1 mL/min, T = 75 °C, t _R1 = 91.3 min, t _R2 = 93.1 min). IR (film): 3054, 1758, 1478 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 8.29 (br s, 1 H), 5.73 (m, 1 H), 5.15-5.08 (m, 2 H), 2.39 (dd, J = 14.0, 6.5 Hz, 1 H), 2.13 (dd, J = 13.5, 8.0 Hz, 1 H), 1.87 (d, J = 14.5 Hz, 1 H), 1.45 (d, J = 15.0 Hz, 1 H), 1.29 (s, 3 H), 1.25 (s, 9 H), 0.96 (s, 9 H). ¹³C NMR (125 MHz, CDCl₃): δ = 174.9, 174.3, 132.8, 119.5, 52.7, 47.9, 47.1, 40.5, 31.7, 31.2, 27.1, 21.7. HRMS: m/z calcd for C₁₆H₂₉NO₂Na⁺: 290.2090; found: 290.2080.
2-Cyclohexylmethyl-2-methylpent-4-enoic Acid (2,2-Dimethyl-propionyl)amide (20)Mp 90-91 °C; R _f = 0.33 (hexane-EtOAc, 4:1); 64% ee (1.6 mL/min, T = 123 °C, t _R1 = 46.3 min, t _R2 = 46.9 min). IR (film): 3054, 1758, 1479 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.24 (br s, 1 H), 5.75 (m, 1 H), 5.16-5.08 (m, 2 H), 2.38 (dd, J = 14.0, 6.8 Hz, 1 H), 2.18 (ddt, J _d = 14.0, 8.0 Hz, J _t = 1.2 Hz, 1 H), 1.69-1.56 (m, 7 H), 1.40-1.35 (m, 2 H), 1.25 (s, 9 H), 1.20 (s, 3 H), 1.18-1.06 (m, 2 H), 0.99-0.88 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 175.0, 174.3, 133.1, 119.2, 47.38, 47.35, 44.7, 35.1, 34.3, 34.2, 27.1, 26.31, 26.27, 26.1, 21.5. HRMS: m/z calcd for C₁₈H₃₁NO₂Na⁺: 316.2246; found: 316.2256.