Petasis Boronic Mannich Reactions of Electron-Poor Aromatic Amines under Microwave Conditions

Abstract

The Petasis reaction of electron-poor aromatic amines such as aminopyridines under microwave irradiation conditions is described. The process provides rapid access to a number of unnatural N-aryl-α-amino acids. The influence of the electronic demand of the boronic acids on the yields is discussed. A comparison with conventional heating is provided.

Key words

amino acids - boron - green chemistry - heterocycles - multicomponent reactions

References

• 1 For a review, see: Williams RM. Hendrix JA. Chem. Rev.  1992,  92:  889 
• 2 McCormick MH. Stark WM. Pittenger GF. Pittenger RC. McGuire GM. Antibiot. Annu.  1955-1956,  606 
• 3a Nagarajan R. Antimicrob. Agents Chemother.  1991,  35:  605 
• 3b Coronelli C. Bardone MR. DePaoli A. Ferrari P. Tuan G. Gallo GG. J. Antibiot.  1984,  37:  627 
• 3c Hunt AH. Molloy RM. Occolowitz JL. Marconi GG. Debono MJ. J. Am. Chem. Soc.  1984,  106:  4891 
• 3d Barna JCJ. Williams DH. Stone DJM. Leung T.-WC. Doddrell DMJ. J. Am. Chem. Soc.  1984,  106:  4895 
• 3e Cavelleri B. Ferrari P. Malabarba A. Magni A. Pallanza R. Gallo GG. J. Antibiot.  1987,  40:  49 
• 4a Townsend CA. Brown AM. J. Am. Chem. Soc.  1983,  105:  913 
• 4b Kamiya T. Hashimoto M. Nakaguchi O. Oku T. Tetrahedron  1979,  35:  323 
• 5 Dhanoa DS. Bagley SW. Chang RSL. Lotti VJ. Chen T.-B. Kivlighn SD. Zingaro GJ. Siegl PKS. Patchett AA. Greenlee WJ. J. Med. Chem.  1993,  36:  4239 
• 6a Watkins J. Collingridge G. Trends Pharm. Sci.  1994,  15:  333 
• 6b Bedingfield JS. Kemp MC. Jane DE. Tse HW. Roberts PJ. Br. J. Pharmacol.  1995,  116:  3323 
• 7a Kuritz P. In Houben-Weyl, Methoden der organischen Chemie   Vol. 8:  Thieme; Stuttgart: 1952.  p.274 
• 7b Gröger H. Chem. Rev.  2003,  103:  2795 
• 8 For a recent review, see: Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 9a Petasis NA. Zavialov IA. J. Am. Chem. Soc.  1997,  119:  445 
• 9b Petasis NA. Goddman A. Zavialov IA. Tetrahedron Lett.  1997,  53:  16463 
• 9c Petasis NA. Zavialov IA. J. Am. Chem. Soc.  1998,  120:  11798 
• 9d Petasis NA. Tetrahedron Lett.  2001,  42:  539 
• 9e Surya Prakash GK. Mandal M. Schweizer S. Petasis NA. Olah GA. J. Org. Chem.  2002,  67:  3718 
• 10 For a review on microwave chemistry: Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
• 12 During the preparation of this work another contribution reporting Petasis reactions under microwave conditions was published. See: McLean NJ. Tye H. Whittaker M. Tetrahedron Lett.  2004,  45:  993 
• 13 General Procedure of (4-Methoxyphenyl)-(pyridin-3-ylamino) Acetic Acid (7b). 3-Aminopyridine (5, 23.5 mg, 0.25 mmol), 4-methoxy phenyl boronic acid (6b, 38 mg, 0.25 mmol) and 1.2 equiv glyoxylic acid monohydrate (28 mg, 0.30 mmol) were suspended in 2 mL MeCN and 0.2 mL DMF. The slurry was heated in a capped microwave vial using magnetic stirring for 5 min at 120 °C (300 W, method A) or heated in a screw cap vial under stirring for 0.5-4 h in a preheated aluminum block (method B). After cooling down to r.t. the liquid was filtered and injected in a preparative HPLC system without any further workup. The fractions containing product were freeze-dried yielding 70 mg (87%) of a colorless foam. ESI⁺: m/z calcd for C₁₄H₁₄N₂O₃ [M⁺]: 258.1004; found: 259.1077 [M + H]⁺). ¹H NMR [500 MHz, (CD₃)₂SO]: δ = 5.33 (1 H, d, J = 4.9 Hz, NCH), 6.95 (2 H, d, J = 8.6 Hz, phenyl), 7.40 (2 H, d, J = 8.6 Hz, phenyl), 7.69 (2 H, m, pyridine), 8.04 (1 H, br dd, J = 4.3, 1.9 Hz, pyridine), 8.15 (1 H, br s, pyridine)

11

Microwave system employed: Personal Chemistry’s Emrys Optimizer. See: www.biotage.com.