ORGANIC LETTERS
Oxaziridine-Mediated Amination of Primary Amines: Scope and Application to a One-Pot Pyrazole Synthesis
2005 Vol. 7, No. 4 713-716
Alan Armstrong,*,† Lyn H. Jones,‡ Jamie D. Knight,† and Richard D. Kelsey† Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, U.K., and Pfizer Global R&D, Department of DiscoVery Chemistry, Sandwich, Kent CT13 9NJ, U.K. Org. Lett. 2005.7:713-716. Downloaded from pubs.acs.org by UNIV OF TEXAS AT EL PASO on 11/02/18. For personal use only.
[email protected] Received December 13, 2004
ABSTRACT
Electrophilic amination of primary aliphatic and aromatic amines is reported using a diethylketomalonate-derived oxaziridine to afford the corresponding N-Boc hydrazines in good to excellent yields. The method allows a one-pot synthesis of pyrazoles from primary amines.
Electrophilic amination provides a conceptually powerful means for the incorporation of nitrogen into molecular frameworks.1 Pioneering work by Collet and co-workers has established that aldehyde-derived N-Boc-oxaziridines such as 1 and 2 can effect electrophilic amination of various nucleophiles.2 However, oxidation often competes with amination in their reaction with heteroatom nucleophiles. They cleanly convert secondary amines to the corresponding protected hydrazines,3 but low yields are observed with primary amines since these undergo competitive imine ‡
Pfizer Global R&D. Imperial College London. (1) Reviews: (a) Erdik, E.; Ay, M. Chem. ReV. 1989, 89, 1947-1980. (b) Greck, C.; Genet, J. P. Synlett 1997, 741-748. (c) Mulzer, J.; Altenbach, H. -J. Organic Synthesis Highlights; VCH: Weinheim, Germany, 1991; p 45-53. (d) Dembach, P.; Seconi, G.; Ricci, A. Chem. Eur. J. 2000, 6, 12811286. (e) Genet, J. P.; Greck, C.; Lavergne, D. In Modern Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinham, Germany, 2000; pp 65102. (2) (a) Vidal, J.; Damestoy, S.; Guy, L.; Hannachi, J.-C.; Aubry A.; Collet, A. Chem. Eur. J. 1997, 3, 1691-1709.(b) Vidal, J.; Hannachi, J.C.; Hourdin, G.; Mulatier J.-C.; Collet, A. Tetrahedron Lett. 1998, 39, 8845-8848. (3) (a) Vidal, J.; Drouin, J.; Collet, A. J. Chem. Soc. Chem. Commun. 1991, 435-437. (b) Vidal, J.; Guy, L.; Ste´rin, S.; Collet, A. J. Org. Chem. 1993, 58, 4791-4793. (c) Vidal, J.; Damestoy, S.; Collet, A. Tetrahedron Lett. 1995, 36, 1439-1442. (d) Hannachi, J.-C.; Vidal, J.; Mulatier, J.-C.; Collet, A. J. Org. Chem. 2004, 69, 2367-2373. †
10.1021/ol0474507 CCC: $30.25 Published on Web 01/20/2005
© 2005 American Chemical Society
formation with the aldehyde released when the oxaziridines effect amination.2 Recently we have reported the novel N-Boc-oxaziridine 3 as an extremely effective nitrogen transfer reagent for the electrophilic amination of a range of allylic and propargylic sulfides which subsequently underwent [2,3]-sigmatropic rearrangement.4 We reasoned that 3 may effect efficient amination of primary amines since the byproduct of amination is a ketone, diethyl ketomalonate. The product N-protected alkyl hydrazines are potentially highly useful for the construction of a large range of valuable heterocycles,5 but very few are commercially available, providing a strong stimulus for the investigation of this chemistry.6 Here we report our successful studies in this area, and the development of a one-pot synthesis of pyrazoles from primary amines. (4) (a) Armstrong, A.; Cooke, R. S. Chem. Commun. 2002, 904-905. (b) Armstrong, A.; Cooke, R. S.; Shanahan, S. E. Org. Biomol. Chem. 2003, 1, 3142-3143. (5) Monosubstituted hydrazines are important intermediates en route to the synthesis of, for example, pyrazoles: (a) Stauffer, S. R.; Huang, Y. R.; Aron, Z. D.; Coletta, C. J.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Bioorg. Med. Chem. 2001, 9, 151-161. Indazoles (b) Boudreault, N.; Leblanc, Y. Org. Synth. 1996, 74, 241-247. Imidazolinones (c) Bozzini, S.; Nitti, P.; Pitacco, G.; Pizzioli, A.; Russo, C. J. Heterocycl. Chem. 1996, 33, 1217-1221. Cinnolines (d) Wunsch, B.; Nerdinger, S.; Hofner, G. Liebigs Ann. 1995, 1303-1312.
Table 1. Amination of 2-Phenylethylamine 8a Using Oxaziridine 3a
Our original reported synthesis of oxaziridine 34a involved aza-Wittig reaction of diethyl ketomalonate with an iminophosphorane derived from (potentially hazardous) N-Bocazide, followed by oxidation of the resulting imine with mCPBA/BuLi. An early aim was to develop an improved synthesis. We developed a novel route to 3 that is amenable to large-scale synthesis (Scheme 1).
Scheme 1. Novel Route to Oxaziridine 3a
entry
solvent
9a (%)
10a (%)
3 (%)
1 2 3 4 5 6 7 8 9b
CH2Cl2 Et2O THF Acetone Petrol PhCH3 CH3CN EtOH CH2Cl2
41 45 48 52 54 62 37 50 75
8 15 19 18 22
