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Synlett 2006(2): 219-222  
DOI: 10.1055/s-2005-923594
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of β-Amino Esters by Bismuth Triflate Catalyzed Three-Component Mannich-Type Reaction

Thierry Ollevier*, Etienne Nadeau
Département de Chimie, Université Laval, Québec, Québec G1K 7P4, Canada
Fax: +1(418)6565034; e-Mail: thierry.ollevier@chm.ulaval.ca;
Further Information

Publication History

Received 31 October 2005
Publication Date:
23 December 2005 (online)

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Abstract

We have developed an efficient, bismuth-catalyzed, Mannich-type three-component reaction by combining the corresponding aldehyde, amine, and silyl ketene acetal. The reaction proceeds rapidly and affords the corresponding β-amino esters in high yields (up to 90%).

Key words

amino esters - bismuth - green chemistry - Mannich-type reaction - multicomponent reactions (MCR) - silyl enolates

16

General Procedure for the Bismuth-Catalyzed Mannich-Type Reaction.
Under an inert atmosphere of argon, the silyl ketene acetal (1.2 mmol) in 1 mL of dry THF was added dropwise to a solution of Bi(OTf)3·nH2O (0.02 mmol), the aldehyde (distilled, except p-nitrobenzaldehyde; 1 mmol), and the aniline (1 mmol) in 1 mL of dry THF at -78 °C. The mixture was stirred at -78 °C (Method A) or stirred at -78 °C for 0.15 h and then allowed to reach r.t. (Method B). The mixture was stirred until the reaction was completed as indicated by TLC. The reaction was quenched with H2O (4 mL) and extracted with Et2O (3 × 20 mL). The organic phase was washed with H2O and sat. aq NaCl, dried over MgSO4, and concentrated under vacuum (rotary evaporator). If the crude product was a solid, it was triturated with hexane (10 mL) and filtered; otherwise, it was purified by column chromatography (eluent hexane-EtOAc). The spectral data for 4b-h,j-n match with those reported in the literature.
Phenyl 3-Phenyl-3-( N -phenylamino)propanoate ( 4a). Reagents: benzaldehyde (102 µL, 106 mg, 1.0 mmol), aniline (91 µL, 93 mg, 1.0 mmol), (1-phenoxyvinyloxy)tri-methylsilane (250 mg, 1.2 mmol), and Bi(OTf)3·nH2O (14 mg, 0.02 mmol). The reaction was stirred for 3.5 h at -78 °C (Method A). The crude product was washed with hexane to afford 265 mg (84%) of 4a as a white solid; mp 129-130 °C; R f = 0.55 (hexane-EtOAc = 4:1). IR (KBr): ν = 3401, 1735 cm-1. 1H NMR (CDCl3): δ = 7.44 (2 H, d, J = 7.6 Hz), 7.26-7.38 (5 H, m), 7.21 (1 H, tt, J = 7.4, 1.3 Hz), 7.12 (2 H, dd, J = 8.6, 7.4 Hz), 6.89-6.91 (2 H, m), 6.70 (1 H, t, J = 7.3 Hz), 6.61 (2 H, dd, J = 8.6, 1.0 Hz), 5.00 (1 H, t, J = 6.3 Hz), 4.59 (1 H, s), 3.07 (2 H, d, J = 6.6 Hz). 13C NMR (CDCl3): δ = 170.0, 150.6, 146.9, 141.9, 129.7, 129.5, 129.2, 128.00, 126.6, 126.3, 121.7, 118.3, 114.0, 55.3, 43.0. HRMS:
m/z calcd for C21H19NO2 [M+]: 317.1416; found: 317.1421.
(S )- tert -Butyl 3-Phenyl-3-( N -phenylamino)propane-thioate ( 4i). Reagents: benzaldehyde (102 µL, 106 mg, 1.0 mmol), aniline (91 µL, 93 mg, 1.0 mmol), [1-(tert-butylthio)vinyl-oxy]trimethylsilane (245 mg, 1.2 mmol), and Bi(OTf)3·nH2O (14 mg, 0.02 mmol). The reaction was stirred for 0.15 h at -78 °C, then allowed to reach r.t. for 1 h (Method B). The crude product was washed with hexane to afford 265 mg (85%) of 4i as an orange solid; mp 99-101 °C. R f = 0.75 (hexane-EtOAc = 4:1). IR (KBr): ν = 3391, 1664 cm-1. 1H NMR (CDCl3): δ = 7.29-7.38 (4 H, m), 7.24 (1 H, tt, J = 7.0, 2.4 Hz), 7.09 (2 H, dd, J = 8.4, 7.4 Hz), 6.67 (1 H, t, J = 7.3 Hz), 6.56 (2 H, d, J = 8.0 Hz), 4.79 (1 H, t, J = 6.7 Hz), 2.90 (2 H, d, J = 6.8 Hz), 1.40 (9 H, s). 13C NMR (CDCl3): δ = 198.3, 147.1, 142.3, 129.3, 129.0, 127.7, 126.5, 117.9, 113.9, 56.1, 52.3, 48.9, 29.9. HRMS: m/z calcd for C19H23NOS [M+]: 313.1500; found: 313.1508.