Synlett 2006(2): 211-214  
DOI: 10.1055/s-2005-923588
LETTER
© Georg Thieme Verlag Stuttgart · New York

Vitamin B12 Catalyzed Radical Cyclizations of Arylalkenes

Chris M. McGinley, Heather A. Relyea, Wilfred A. van der Donk*
Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
Fax: +1(217)2448024; e-Mail: vddonk@uiuc.edu;
Further Information

Publication History

Received 29 July 2005
Publication Date:
23 December 2005 (online)

Abstract

The use of vitamin B12 for synthetic organic transformations has been extensively studied. Herein, we report the intra­molecular cyclization reaction of a series of arylalkene substrates catalyzed by vitamin B12. These reactions proceed in good yields in environmentally benign solvents and do not require the use of a ­toxic heavy metal catalyst. Variation of the reaction pH can predictably alter the product distribution.

    References and Notes

  • 1 Brown KL. Chem. Rev.  2005,  105:  2075 
  • 2 Shey J. McGinley CM. McCauley KM. Dearth A. Young B. van der Donk WA. J. Org. Chem.  2002,  67:  837 
  • 3a Forbes CL. Franck RW. J. Org. Chem.  1999,  64:  1424 
  • 3b Kleban M. Kautz U. Greul J. Hilgers P. Kugler R. Dong H.-Q. Jager V. Synthesis  2000,  1027 
  • 3c Huang L. Chen Y. Gao G.-Y. Zhang XP. J. Org. Chem.  2003,  68:  8179 
  • 3d Chen Y. Zhang XP. J. Org. Chem.  2004,  69:  2431 
  • 3e Shimakoshi H. Tokunaga M. Kuroiwa K. Kimizuka N. Hisaeda Y. Chem. Commun.  2004,  50 
  • 4a Zhang ZD. Scheffold R. Helv. Chim. Acta  1993,  76:  2602 
  • 4b Su H. Walder L. Zhang ZD. Scheffold R. Helv. Chim. Acta  1988,  71:  1073 
  • 4c Fischli A. Helv. Chim. Acta  1982,  65:  2697 
  • 5 Keck GE. McHardy SF. Murry JA. J. Org. Chem.  1999,  64:  4465 
  • 6 Keck GE. Wager TT. Rodriquez JFD. J. Am. Chem. Soc.  1999,  121:  5176 
  • 7 Lexa D. Savéant J. J. Chem. Soc., Chem. Commun.  1975,  872 
  • 8 Waddington MD. Finke RG. J. Am. Chem. Soc.  1993,  115:  4629 
  • 9 Baldwin DA. Betterton EA. Chemaly SM. Pratt JM. J. Chem. Soc., Dalton Trans.  1985,  1613 
  • 10 Ng FTT. Rempel GL. Mancuso C. Halpern J. Organometallics  1990,  9:  2762 
  • 11 Garr CD. Finke RG. J. Am. Chem. Soc.  1992,  114:  10440 
  • 12 Holliger C. Pierik AJ. Reijerse EJ. Hagen WR. J. Am. Chem. Soc.  1993,  115:  5651 
  • 13 Gaertner P. Weiss DS. Harms U. Thauer RK. Eur. J. Biochem.  1994,  226:  465 
14

Solvents used for cyclization reactions were deoxygenated under reduced pressure (10 min) and purged with N2; this was repeated three times before storage under argon. When t-BuOH was used as a solvent, it was distilled over CaH2. All cyclizations were conducted on a 0.1 mmol scale, and initiated in the dark before covering the flask with aluminum foil. Representative procedures are provided for a select set of substrates.
A flask was charged with 1d (20.3 mg, 0.116 mmol) and vitamin B12 (12.8 mg, 0.009 mmol) and purged with Ar. Degassed t-BuOH (15 mL) was added, followed by a Ti(III) citrate solution, pH 6.0 (8 mL) prepared as previously described. [2] The purple solution was stirred in the dark for 24 h. The reaction was poured into H2O (50 mL) and extracted with hexane (3 × 50 mL). The combined organic layers were washed with H2O (2 × 75 mL), dried with MgSO4, filtered and concentrated, yielding 15.9 mg of total product (1:14 mixture of 2d and 3d, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.07 (s, 3 H), 1.41 (s, 3 H), 1.75 (s, 3 H), 3.12 (t, J = 7.9 Hz, 1 H), 4.01 (m, 2 H), 4.79 (m, 1 H), 4.95 (pentet, J = 1.5 Hz, 1 H), 5.73 (dd, J = 3.6, 1.3 Hz, 1 H), 6.19 (t, J = 2.9 Hz, 1 H), 6.53 (dd, J = 2.6, 1.3 Hz, 1 H). 13C NMR (100.6 MHz, CDCl3): δ = 23.0 (CH3), 23.8 (CH3), 28.6 (CH3), 41.4 (Cq), 48.7 (CH2), 60.5 (CH), 96.7 (CH), 111.5 (CH), 113.1 (CH), 113.6 (CH2), 143.0 (Cq). HRMS (EI): m/z calcd for C12H17N [M+]: 175.1361; found: 175.1360.
A flask was charged with 7b (29.4 mg, 0.090 mmol) and vitamin B12 (12.4 mg, 0.009 mmol) and purged with Ar. Degassed MeCN (20 mL) was added followed by aqueous Ti(III) citrate pH 8.0 (7 mL). The purple solution was stirred in the dark for 23 h, then poured into H2O (50 mL) and extracted with hexane (3 × 50 mL). The combined organic layers were washed with H2O (2 × 75 mL), dried with MgSO4, filtered and concentrated yielding 20.0 mg of product 8b (68%) as a colorless oil. Both diastereomers were separated by HPLC and the stereochemistry of the major isomer was determined using NOE after assignment of the protons by HMQC and COSY spectroscopy. 1H NMR (500 MHz, CDCl3, major diastereomer): δ = 1.47 (s, 3 H), 3.63 (m, 2 H), 3.77 (d, J = 8.8 Hz, 1 H), 3.87 (d, J = 7.7 Hz, 1 H), 3.98 (dt, J = 1.8, 7.4 Hz, 1 H), 4.22 (d, J = 8.8 Hz, 1 H), 6.84-6.90 (m, 3 H), 7.05-7.35 (m, 12 H). Minor diastereomer: δ = 1.57 (s, 3 H), 3.16 (d, J = 11.4 Hz, 1 H), 3.38 (m, 1 H), 3.52 (dd, J = 10.2, 9.7 Hz, 1 H), 3.85 (dd, J = 8.1, 8.3 Hz, 1 H), 3.91 (d, J = 8.6 Hz, 1 H), 4.21 (d, J = 8.7 Hz, 1 H), 7.05-7.35 (m, 15 H). 13C NMR (125.6 MHz, CDCl3, major diastereomer): δ = 18.7 (CH3), 47.9 (CH2), 55.0 (CH), 77.0 (CH2), 85.0 (CH2), 125.7 (CH), 126.0 (CH), 126.7 (CH), 127.5 (CH), 128.0 (CH), 128.1 (CH), 128.9 (CH), 144.4 (Cq). HRMS (EI): m/z calcd for C24H24O [M+]: 328.1827; found: 328.1826
A flask was charged with 7d (18.8 mg, 0.093 mmol) and vitamin B12 (13.2 mg, 0.01 mmol) and purged with Ar. Degassed MeCN (20 mL) was added, followed by aqueous Ti(III) citrate pH 6.0 (8 mL). The dark red solution was stirred in the dark for 24 h, and then the reaction was poured into H2O (50 mL) and extracted with hexane (3 × 60 mL). The combined organic layers were washed with H2O (2 × 75 mL), dried with MgSO4, filtered and concentrated yielding 15.4 mg of product 9d (82%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.37 (s, 3 H), 1.48 (s, 3 H), 3.11 (t, J = 8.1 Hz, 1 H), 3.82 (d, J = 8.6 Hz, 1 H), 4.05 (t, J = 8.8 Hz, 1 H), 4.18 (d, J = 8.7 Hz, 1 H), 4.15 (t, J = 8.2 Hz, 1 H), 4.70 (s, 1 H), 4.89 (s, 1 H), 7.25-7.35 (m, 3 H), 7.48-7.50 (m, 2 H). 13C NMR (125.6 MHz, CDCl3): δ = 19.8 (CH3), 24.2 (CH3), 57.5 (CH), 71.4 (CH2), 82.7 (CH2), 112.4 (CH2), 126.5 (CH), 127.4 (CH), 128.1 (CH), 128.6 (CH), 146.5 (Cq). HRMS (EI): m/z calcd for C14H18O [M+]: 202.1358; found: 202.1357.