SmI₂-Mediated Reductive Cross-Coupling Reactions of α-Cyclopropyl Nitrones

Abstract

Three new α-cyclopropyl nitrones have been synthesized as mechanistic probes for reductive cross-coupling reactions of ­nitrones. The α-cyclopropylcarbinyl radical intermediate formed by single electron transfer from SmI₂ to these nitrones is not prone to ring opening, due to a unique stabilization by the vicinal N-O-Sm system. Consequently, β-cyclopropyl hydroxylamines could be prepared in high yield from α-cyclopropyl nitrones.

Key words

nitrone - samarium diiodide - reductive coupling reaction - mechanistic probes - cyclopropyl group

References and Notes

• For reviews on the use of SmI₂ in cascade reactions and in total synthesis, see:
• 1a Nicolaou KC. Ellery SP. Chen JS. Angew. Chem. Int. Ed.  2009,  48:  7140 
• 1b Edmonds DJ. Johnston D. Procter DJ. Chem. Rev.  2004,  104:  3371 
• 1c Kagan HB. Tetrahedron  2003,  59:  10351 
• 1d Krief A. Laval A.-M. Chem. Rev.  1999,  99:  745 
• 1e Molander GA. Harris CR. Chem. Rev.  1996,  96:  307 
• 2a Girard P. Namy JL. Kagan HB. J. Am. Chem. Soc.  1980,  102:  2693 
• 2b Kagan HB. Namy JL. Girard P. Tetrahedron Suppl.  1981,  37:  175 
• 3a Cammoun C. Zriba R. Bezzenine-Lafollée S. Guibé F. Tetrahedron  2007,  63:  3728 
• 3b Hansen AM. Lindsay KB. Antharjanam PKS. Karaffa J. Daasbjerg K. Flowers RA. Skrydstrup T. J. Am. Chem. Soc.  2006,  128:  9616 
• 3c McKerlie F. Rudkin IM. Wynne G. Procter D. J. Org. Biomol. Chem.  2005,  3:  2805 
• 3d Tamiya H. Goto K. Matsuda F. Org. Lett.  2004,  6:  545 
• 3e Hutton TK. Muir KW. Procter DJ. Org. Lett.  2003,  5:  4811 
• 3f Curran DP. Gu X. Zhang W. Dowd P. Tetrahedron  1997,  53:  9023 
• 3g Curran DP. Fevig TL. Jasperse CP. Totleben MJ. Synlett  1992,  943 
• 3h Molander GA. McKie JA. J. Org. Chem.  1991,  56:  4112 
• 4 Berger DJ. Tanko JM. Radical Anions and Radical Cations Derived from Compounds Containing C=C, C=O, or C=N groups   Patai S. John Wiley & Sons, Ltd.; New York: 1997.  p.1281-1354  
• 5a Tanko JM. Phillips JP. J. Am. Chem. Soc.  1999,  121:  6078 
• 5b Stevenson JP. Jackson WF. Tanko JM.
  J. Am. Chem. Soc.  2002,  124:  4271 
• 5c Chahma M. Li X. Phillips JP. Schwartz P. Brammer LE. Wang Y. Tanko JM. J. Phys. Chem. A  2005,  109:  3372 
• 6a Batey RA. Motherwell WB. Tetrahedron Lett.  1991,  32:  6649 
• 6b Molander GA. Alonso-Alija C. Tetrahedron  1997,  53:  8067 
• 6c Lee PH. Lee J. Tetrahedron Lett.  1998,  39:  7889 
• 6d Nivlet A. Le Guen V. Dechoux L. Le Gall T. Mioskowski C. Tetrahedron Lett.  1998,  39:  2115 
• 6e Molander GA. Harris CR. Tetrahedron  1998,  54:  3321 
• 6f Sheikh SE. Kausch N. Lex J. Neudörfl J.-M. Schmalz H.-G. Synlett  2006,  1527 
• 6g Aulenta F. Hölemann A. Reissig H.-U. Eur. J. Org. Chem.  2006,  1733 
• 7a Kusama H. Hara R. Kawahara S. Nishimori T. Kashima H. Nakamura N. Morihira K. Kuwajima I.
  J. Am. Chem. Soc.  2000,  122:  3811 
• 7b El Sheikh S. Meier zu Greffen A. Lex J. Neudörfl J.-M. Schmalz H.-G. Synlett  2007,  1881 
• 7c Shenvi RA. Guerrero CA. Shi J. Li C.-C. Baran PS. J. Am. Chem. Soc.  2008,  130:  7241 
• 8 Foster SL. Handa S. Krafft M. Rowling D. Chem. Commun.  2007,  4791 
• 9a Masson G. Py S. Vallée Y. Angew. Chem. Int. Ed.  2002,  41:  1772 
• 9b Burchak ON. Philouze C. Chavant PY. Py S. Org. Lett.  2008,  10:  3021 
• 10a For a review on the synthesis of vicinal amino alcohols by reductive cross-coupling reactions, see: Burchak ON. Py S. Tetrahedron  2009,  65:  7333 
• 10b See also: Wu S.-F. Zheng X. Ruan Y.-P. Huang P.-Q. Org. Biomol. Chem.  2009,  7:  2967 
• 11a Masson G. Cividino P. Py S. Vallée Y. Angew. Chem. Int. Ed.  2003,  42:  2265 
• 11b Riber D. Skrydstrup T. Org. Lett.  2003,  5:  229 
• 11c Desvergnes S. Py S. Vallée Y. J. Org. Chem.  2005,  70:  1459 
• 12a Tanko JM. Drumright RE. J. Am. Chem. Soc.  1990,  112:  5362 
• 12b Tanner DD. Chen JJ. Luelo C. Peters PM. J. Am. Chem. Soc.  1992,  114:  713 
• 13 Dondoni A. Franco S. Junquera F. Merchán F. Merino P. Tejero T. Synth. Commun.  1994,  24:  2537 
• 14a Baldwin JE. Patapoff TW. Barden TC. J. Am. Chem. Soc.  1984,  106:  1421 
• 14b Zelechonok Y. Silverman RB. J. Org. Chem.  1992,  57:  5785 
• 15 Tripoli R. Cayzer TN. Willis AC. Sherburn MS. Paddon-Row MN. Org. Biomol. Chem.  2007,  5:  2606 
• 17a Hilmersson G. Dahlén A. Eur. J. Inorg. Chem.  2004,  3393 ; and references therein
• 17b Prasad E. Flowers RA. J. Am. Chem. Soc.  2005,  127:  18093 
• 17c Amiel-Levy M. Hoz S. J. Am. Chem. Soc.  2009,  131:  8280 
• 18a Russell GA. Dedolph DF. J. Org. Chem.  1985,  50:  2498 
• 18b Pasto DJ. Krasnansky R. Zercher C. J. Org. Chem.  1987,  52:  3062 
• 18c Wayner DDM. Clark KB. Rauk A. Yu D. Armstrong DA. J. Am. Chem. Soc.  1997,  119:  8925 
• 19a For a review on biological activities of cyclopropane derivatives, see: Salaün J. Top. Curr. Chem.  2000,  207:  1 
• For selected examples of bioactive α-cyclopropylmethyl amines, see:
• 19b Shimamoto K. Ohfune Y. J. Med. Chem.  1996,  39:  407 
• 19c Laroche C. Behr J.-B. Szymoniak J. Bertus P. Schütz C. Vogel P. Plantier-Royon R. Bioorg. Med. Chem.  2006,  14:  4047 
• 19d Devreux V. Wiesner J. Goeman JL. Van der Eycken J. Jomaa H. Van Calenbergh S. J. Med. Chem.  2006,  49:  2656 

16

General Procedure for the Coupling Reaction of Nitrones 1-3 and Cyclohexanone; Conditions A: To a stirred and carefully deoxygenated solution of nitrone 1-3 (0.20 mmol) and cyclohexanone (0.30 mmol) in anhyd THF (5 mL), a 0.1 M solution of SmI₂ (0.44 mmol) was added at -78 ˚C under argon. After 3 h, sat. solutions of Na₂S₂O₃ (5 mL) and NaHCO₃ (5 mL), and EtOAc (20 mL) were added. After extraction, the organic phases were washed with brine, dried over Na₂SO₄, filtered, and concentrated. Column chromatography yielded racemic products 11-13 (EtOAc-pentane, 1:4) and recovered nitrones 1-3 (MeOH-EtOAc, 5:95). Conditions B. The same procedure was used, but degassed H₂O (3.20 mmol) was added before SmI₂ addition (0.6 mmol).