Download PDF
Synlett 2007(14): 2197-2200  
DOI: 10.1055/s-2007-984913
LETTER
© Georg Thieme Verlag Stuttgart · New York

Heteropoly Acids Catalyzed Direct Mannich Reactions: Three-Component Synthesis of N-Protected β-Amino Ketones

Rui Wang, Taikun Huang, Lin Shi, Bogang Li, Xiaoxia Lu*
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. of China
Fax: +86(28)85222753; e-Mail: luxx@cib.ac.cn;
Further Information

Publication History

Received 10 May 2007
Publication Date:
20 July 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

Heteropoly acids efficiently catalyzed one-pot three-component Mannich reactions of aryl aldehydes, aryl ketones, and carbamates at ambient temperature and afforded the corresponding N-protected β-amino ketones in good to excellent yields. This method provides a novel and improved modification of three-component Mannich reactions in terms of a wide scope of aldehydes, ketones and carbamates, economic viability and reusability.

Key words

heteropoly acids - one-pot - Mannich reaction - N-protected β-amino ketones

16

Typical Procedure for the Synthesis of N-Protected β-Amino Ketones To a solution of HPAs (5 mol%) in MeCN (1.0 mL) were added ethyl carbamate (1.5 mmol), benzaldehyde (1.0 mmol), and acetophenone (2.0 mmol) successively at r.t. After the mixture was stirred for 24 h, a sat. aq NaHCO3 solution (5 mL) and brine (5 mL) were added, and the mixture was extracted with EtOAc. The organic phase was dried (anhyd Na2SO4) and filtered. The filtrate was evaporated under reduced pressure. The crude product was purified by silica gel chromatography and gave the desired product.
Compound 4d: mp 96-97 °C. 1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 7.4 Hz, 2 H), 7.53 (t, J = 7.4 Hz, 1 H), 7.42 (t, J = 8.0 Hz, 2 H), 7.20 (t, J = 8.0 Hz, 1 H), 6.76-6.93 (m, 3 H), 5.70 (br s, 1 H), 5.25 (dd, J 1 = 6.0 Hz, J 2 = 13.6 Hz, 1 H), 4.08 (dd, J 1 = 7.0 Hz, J 2 = 14.1 Hz, 2 H), 3.77 (s, 3 H), 3.65 (m, 1 H), 3.40 (dd, J 1 = 5.8 Hz, J 2 = 16.7 Hz, 1 H), 1.20 (t, J 1 = 6.7 Hz, J 2 = 14.0 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 197.8, 159.8, 155.9, 143.2, 136.7, 133.3, 129.7, 128.7, 128.1, 118.6, 112.7, 112.4, 60.9, 55.2, 51.7, 44.0, 14.6. ESI-HRMS: m/z calcd for [C19H21NO4 + Na]+: 350.3641; found: 350.3638.
Compound 4j: mp 116-117 °C. 1H NMR (600 MHz, CDCl3): δ = 8.24 (s, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 7.88 (d, J = 7.4 Hz, 2 H), 7.73 (d, J = 7.2 Hz, 1 H), 7.56 (t, J = 7.4 Hz, 1 H), 7.44-7.50 (m, 3 H), 5.99 (br s, 1 H), 5.38 (dd, J 1 = 5.6 Hz, J 2 = 13.0 Hz, 1 H), 4.09 (dd, J 1 = 7.0 Hz, J 2 = 14.2 Hz, 2 H), 3.72-3.75 (m, 1 H), 3.50 (dd, J 1 = 5.4 Hz, J 2 = 17.4 Hz, 1 H), 1.23 (t, J 1 = 6.4 Hz, J 2 = 14.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 197.3, 156.0, 148.5, 144.0, 136.3, 133.8, 132.9, 129.5, 128.8, 128.1, 122.4, 121.4, 61.3, 50.9, 43.5, 14.5. ESI-HRMS: m/z calcd for [C18H18N2O5 + Na]+: 365.3358; found: 365.3460.
Compound 4s: mp 81-82 °C. 1H NMR (600 MHz, CDCl3): δ = 7.86 (d, J = 7.7 Hz, 2 H), 7.52 (t, J = 7.1 Hz, 1 H), 7.40 (t, J = 7.6 Hz, 2 H), 7.19-7.31 (m, 6 H), 6.88 (t, J = 7.7 Hz, 2 H), 6.75 (dd, J 1 = 2.2 Hz, J 2 = 8.2 Hz, 1 H), 5.86 (br s, 1 H), 5.28 (dd, J 1 = 6.2 Hz, J 2 = 13.1 Hz, 1 H), 5.05-5.10 (m, 2 H), 3.74 (s, 3 H), 3.65 (m, 1 H), 3.39 (dd, J 1 = 5.2 Hz, J 2 = 16.5 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 197.8, 159.8, 155.7, 136.7, 136.5, 133.4, 129.7, 128.7, 128.5, 128.1, 118.6, 112.8, 112.4, 66.8, 55.2, 51.8, 44.0. ESI-HRMS: m/z calcd for [C24H23NO4 + Na]+: 412.4335; found: 412.4330.
Compound 4w: mp 143-144 °C. 1H NMR (600 MHz, CDCl3): δ = 8.15 (d, J = 8.4 Hz, 2 H), 7.86 (d, J = 7.6 Hz, 2 H), 7.34-7.54 (m, 10 H), 6.08 (br s, 1 H), 5.40 (d, J = 6.2 Hz, 1 H), 5.10-5.15 (m, 2 H), 3.73-3.76 (m, 1 H), 3.49 (dd, J 1 = 4.6 Hz, J 2 = 17 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 197.3, 155.7, 148.8, 147.1, 136.2, 133.9, 128.8, 128.3, 127.0, 123.8, 51.2, 43.2. ESI-HRMS: m/z calcd for [C23H20N2O5 + Na]+: 427.4052; found: 427.4055