Diastereoselective Synthesis of 1-Aryl-2-Amino-Cyclopropane Carboxylates

Abstract

Methyl 1-aryl-2-amino-cyclopropane carboxylates have been readily synthesized in high yields by Rh-catalyzed decomposition of aryldiazoacetates in the presence of N-vinylphthalimide. The reaction is highly trans-selective.

Key words

cyclopropanation - diastereoselective - rhodium - diazo­acetates - amino-cyclopropanes

References and Notes

• Leading reviews:
• 1a Seebach D. Matthews JL. Chem. Commun.  1997,  2015 
• 1b Gellman SH. Acc Chem. Res.  1998,  31:  173 
• 2a Diaz M. Ortuño RM. Tetrahedron: Asymmetry  1996,  7:  3465 
• 2b Diaz M. Jiménez J. Ortuño RM. Tetrahedron: Asymmetry  1997,  8:  2465 
• 2c Godier-Marc E. Aitken DJ. Husson H.-P. Tetrahedron Lett.  1997,  38:  4065 
• 3a Reissig HU. Top. Curr. Chem.  1988,  144:  73 
• 3b Reissig H.-U. Zimmer R. Chem. Rev.  2003,  103:  1151 
• 4 Reiser O. Gnad F. Chem. Rev.  2003,  103:  1603 
• 5 Kaiser C. Weinstock J. Org Synth.  1971,  51:  48 
• 6 For a recent example, see: De Kimpe N. Mangelinckx S. Tetrahedron Lett.  2003,  44:  1771 
• 7 Doyle MP. Mckervey MA. Ye T. In Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley-Interscience; New York: 1998.  p.163-220  
• 8 N-Vinylphthalimide is commercially available and has been used in cyclopropanation of aryldiazomethanes. See: Aggarwal VK. Vicente J. Bonnert RV. Org. Lett.  2001,  3:  2785 
• 9 The aryldiazoacetates used in this study were synthesized in high yields according to a literature procedure: Davies HML. Townsend RJ. J. Org. Chem.  2001,  66:  6595 
• 10 Davies HML. Hodges LM. Matasi JJ. Hansen T. Stafford DG. Tetrahedron Lett.  1998,  39:  4417 
• 12 Davies HML. Bruzinski PR. Fall MJ. Tetrahedron Lett.  1996,  37:  4133 
• 13 Davies HML. Nagashima T. Klino JL. Org Lett.  2000,  2:  823 

11

CCDC-286242 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ, UK; fax [phone]; or [e-mail]].

14

Enantiomeric excess measured by chiral HPLC. Absolute stereochemistry not determined.

15

General Experimental Procedure To a solution of Rh₂(OAc)₄ (0.03 mmol) and N-vinylphthal-imide (3.3 mmol) in CH₂Cl₂ (5 mL) at r.t., was added dropwise over 1 h, a solution of aryldiazoacetate (3.0 mmol) in CH₂Cl₂ (10 mL). The resulting solution was stirred for an additional 15 min before the solvent was removed in vacuo. Flash chromatography of the crude product [silica gel, eluting with hexane-Et₂O (1:3)] yielded the desired cyclopropane 2 as a white solid. All cyclopropanes 2a-i were characterized by ¹H NMR and ¹³C NMR spectroscopy, MS, HRMS and melting points.

Spectroscopic data for 2a: ¹H NMR (300 MHz, CDCl₃): δ = 2.14 (dd, 1 H, J = 9.0, 6.3 Hz, CH₂), 3.15 (t, 1 H, J = 6.1 Hz, CH₂), 3.69 (s, 3 H, OCH₃), 3.84 (dd, 1 H, J = 9.0, 5.9 Hz, CH), 7.17 (m, 5 H), 7.61 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 16.9 (CH₂), 34.2 (C), 36.8 (CH), 52.7 (OCH₃), 123.1 (CH), 127.6 (C), 127.7 (CH), 128.0 (CH), 131.1 (CH), 132.9 (C), 134.0 (CH), 168.3 (C=O), 173.0 (C=O). MS (EI): m/z (%) = 321 (6%) [M⁺], 289 (100), 261 (49), 233 (34), 115 (51). HRMS: m/z calcd for C₁₉H₁₅NO₄: 321.1001; found: 321.0989. Mp 145 °C. Crystals of 2a suitable for X-ray crystallography were grown from a solution of pentane and CHCl₃.