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Synlett 2006(1): 0081-0085  
DOI: 10.1055/s-2005-922776
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Brønsted Acid Catalyzed Conjugate Addition of Aryl Methyl Ketone Derived Enamines to Nitroalkenes

Darren J. Dixon*a, Robert D. Richardsonb
a School of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK
Fax: +44(161)2754939; e-Mail: darren.dixon@manchester.ac.uk;
b Cambridge University Chemical Laboratories, Lensfield Road, Cambridge, CB2 1EW, UK
Further Information

Publication History

Received 8 September 2005
Publication Date:
16 December 2005 (online)

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Abstract

A novel Brønsted acid catalyst has been developed for the conjugate addition of aryl methyl ketone derived enamines to ­nitroalkenes in good yield and moderate enantioselectivity.

Key words

Brønsted acid - organocatalysis - nitroalkene - thiourea - enantioselective

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17

Synthesis of 13a.
A solution of (R,R)-(1,2)-diaminocyclohexane (9.5 g, 83 mmol, 1.5 equiv), tetraphenylphthalic anhydride (25 g, 55.2 mmol, 1.0 equiv) and (±)-camphorsulfonic acid (15.4 g, 66.2 mmol, 1.2 equiv) in xylene (750 mL) was refluxed for 16 h. The reaction mixture was allowed to cool to r.t. and the solvent was removed under reduced pressure. The residue was slurried in aq KOH solution (400 mL, 1 mol dm-3) and extracted with CH2Cl2 (3 × 200 mL). The combined organic extracts were dried (K2CO3), filtered and concentrated under reduced pressure. The residue was re-dissolved in THF (500 mL) and 4-nitrophenyl isothiocyanate (29 g, 166 mmol, 3 equiv) was added in three portions at room temperature. The reaction mixture was stirred at r.t. for 18 h, concentrated under reduced pressure and purified by flash column chromatography (20:80 to 100:0 EtOAc-hexane) to give a viscous yellow oil that was re-dissolved in minimal Et2O. Addition of pentane gave the thiourea 13a (8.0 g, 11.0 mmol, 20%) as a yellow powder; mp 150-151 °C; [α]D 25 -61.1
(c 3.43, CHCl3). IR: νmax = 3329, 2988, 2910, 1766, 1703, 1596, 1522, 1371, 1329 cm-1. 1H NMR (500 MHz, d 6-DMSO, 353 K): δ = 9.77 (1 H, br s), 8.11 (2 H, d, J = 9.0 Hz), 7.81 (1 H, br d, J = 7.5 Hz), 7.68 (2 H, d, J = 9.0 Hz), 7.16-7.02 (10 H, m), 6.85-6.63 (10 H, m), 4.85 (1 H, m), 3.95 (1 H, td, J = 12.0, 3.5 Hz), 2.31 (1 H, br q, J = 9.5 Hz), 2.13-2.05 (1 H, m), 1.79-1.74 (3 H, m), 1.32-1.28 (3 H, m). 13C NMR (125 MHz, d 6-DMSO, 353 K): δ = 180.5, 167.0, 147.8, 142.7, 138.9, 138.4, 136.2, 131.0, 130.3, 128.1, 127.29, 127.27, 127.2, 127.1, 126.5, 124.6, 121.1, 54.4, 54.3, 32.1, 28.8, 25.4, 24.8. ESI-MS [ESI - H+]: m/z calcd for C45H37N4O4S+: 729.2530; found: 729.2531.