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Synlett 2006(12): 1841-1846  
DOI: 10.1055/s-2006-947352
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Accelerated Coupling-Isomerization-Enamine Addition-Aldol Condensation Sequences to 1-Acetyl-2-amino-cyclohexa-1,3-dienes

Oana G. Schramm (née Dediu), Thomas J. J. Müller*
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49(6221)546579; e-Mail: Thomas.J.J.Mueller@oci.uni-heidelberg.de;
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Publication History

Received 26 April 2006
Publication Date:
24 July 2006 (online)

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Abstract

The microwave-accelerated consecutive reaction of electron deficient (hetero)aryl bromides 1, (hetero)aryl propargyl alcohols 2, and enamino carbonyl compounds 6 or 8 furnishes 1-acetyl-2-amino-cyclohexa-1,3-dienes 7 or 6-N,N-dimethyl carbamoyl-cyclohexenones 9, respectively, in good yields in the sense of a one-pot coupling-isomerization-enamine addition-aldol condensation sequence.

Key words

alkynes - condensations - cross-couplings - cyclizations - microwave reactions

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Typical Procedure (7a, Entry 1).
A magnetically stirred solution of 182 mg (1.00 mmol) of 1a, 139 mg (1.05 mmol) of 2a, 20 mg (0.02 mmol) of Pd(PPh3)Cl2, and 2 mg (0.01 mmol) of CuI in a degassed mixture of 0.5 mL of Et3N and 1.5 mL of THF in a sealed microwave vial under nitrogen was heated by microwave irradiation to 150 °C for 15 min. After cooling to r.t. 726 mg (3.00 mmol) of enaminone 6a and 0.75 mL of AcOH were added and the reaction mixture was heated by microwave irradiation to 150 °C for another 10 min. After aqueous work-up and chromatography on silica gel (hexane-acetone, 2:1) and recrystallization from acetone 311 mg (68%) of 7a were obtained as yellow crystals. Mp. 227 °C. IR (KBr): 2219, 1632 cm-1.1H NMR (300 MHz, DMSO-d 6): δ = 1.80 (s, 3 H), 2.75-2.81 (m, 1 H), 2.94-3.12 (m, 3 H), 3.68-3.89 (m, 2 H), 4.17 (d, J = 7.0 Hz, 1 H), 6.49 (d, J = 1.9 Hz, 1 H), 7.00-7.05 (m, 3 H), 7.14 (t, J = 7.4 Hz, 1 H), 7.21-7.29 (m, 4 H), 7.32 (d, J = 8.12 Hz, 2 H), 7.36 (d, J = 8.12 Hz, 1 H), 7.62 (d, J = 8.12 Hz, 1 H), 7.69 (d, J = 8.12 Hz, 2 H), 10.92 (s, 1 H), 11.72 (t, J = 6.0 Hz, 1 H). 13C NMR (CDCl3, 75.5 MHz): δ = 26.6 (CH2), 26.9 (CH2), 38.6 (CH3), 34.8 (CH2), 38.2 (CH), 42.4 (CH2), 97.7 (CH) 108.9 (Cquat.), 110.9 (Cquat.), 111.5 (Cquat.), 115.7 (CH), 118.2 (Cquat.), 118.5 (CH), 118.9 (CH), 121.0 (CH), 123.7 (CH), 125.5 (CH), 127.0 (Cquat.), 128.3 (CH), 128.5 (CH), 128.8 (CH), 132.0 (CH), 136.4 (Cquat.), 138.6 (Cquat.), 145.2 (Cquat.), 146.9 (Cquat.), 151.1 (Cquat.), 156.1 (Cquat.), 192.8 (Cquat.). MS (EI, 70 eV): m/z (%) = 457 (14) [M+], 414 (12) [M+ - CH3CO], 327 (44) [M+ - C9H8N+], 144 (4) [C10H10N+], 130 (100) [C9H8N+]. Anal. Calcd for C31H27N3O (457.6): C, 81.40; H, 5.91; N, 9.19. Found: C, 81.02; H, 6.05; N, 9.09.

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All compounds have been fully characterized spectroscopically and by correct elemental analysis or HRMS, respectively.

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Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC-605608 (7a), and CCDC-605609 (9d). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: +44 (1223)336-033; email: deposit@ccdc.cam. ac.uk].

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Typical Procedure (9a, Entry 1).
A magnetically stirred solution of 182 mg (1.00 mmol) of 1a, 139 mg (1.05 mmol) of 2a, 20 mg (0.02 mmol) of Pd(PPh3)Cl2, and 2 mg (0.01 mmol) of CuI in a degassed mixture of 0.5 mL of Et3N and 1.5 mL of THF in a sealed microwave vial under nitrogen was heated by microwave irradiation to 150 °C for 15 min. After cooling to r.t. 576 mg (3.00 mmol) of enaminone 8a and 0.75 mL of AcOH were added and the reaction mixture was heated by microwave irradiation to 150 °C for another 10 min. After work-up and chromatography on silica gel (toluene-acetone, 3:1) and recrystallization from acetone 227 mg (66%) of 9a were obtained as light yellow crystals. Mp. 164 °C. IR (KBr): 2227, 1644, 1608 cm-1.1H NMR (300 MHz, DMSO-d 6): δ = 2.79 (s, 3 H), 2.96 (s, 3 H), 2.99-3.01 (m, 2 H), 3.97 (ddd, J = 6.0, 12.0, 12.0 Hz, 1 H), 4.08 (d, J = 12.0 Hz, 1 H), 6.45 (s, 1 H), 7.31-7.50 (m, 7 H), 7.53 (d, J = 8.16 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 35.3 (CH2), 35.5 (CH3), 37.4 (CH3), 43.6 (CH), 54.7 (CH), 110.6 (Cquat.), 118.5 (Cquat.), 124.2 (CH), 125.5 (CH), 128.1 (CH), 128.7 (CH), 130.4 (CH), 132.7 (CH), 137.3 (Cquat.), 147.6 (Cquat.), 158.1 (Cquat.), 168.3 (Cquat.), 194.8 (Cquat.). MS (EI, 70 eV): m/z (%) = 344 (30) [M+], 300(7) [M+ - C2H6N+], 272 (100) [M+ - C2H6NCO], 244 (6) [M+ - C2H6NCO - CO], 72 (23) [C2H6NCO+]. Anal. Calcd for C22H20N2O2 (344.4): C, 76.72; H, 5.85; N, 8.13. Found: C, 76.96; H, 5.89; N, 8.15.