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DOI: 10.1055/s-0031-1290319
Direct Synthesis of α-Amino Amides from N-Alkyl Amines by the Copper-Catalyzed Oxidative Ugi-Type Reaction
Publikationsverlauf
Publikationsdatum:
25. Januar 2012 (online)
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Abstract
α-Amino amides can be accessed directly form N-alkyl amines by the isocyanide-compatible oxidative copper-peroxide conditions even in the presence of water. Various functional groups are tolerated in the reaction, leading to the synthesis of various α-amino amides in moderate yield. A plausible mechanism is proposed in which an oxidative Ugi-type three-component pathway is supposed to be involved.
Key words
α-amino amide - isocyanide - Ugi reaction - copper catalysis - multicomponent reaction
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- Supporting Information
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References and Notes
Representative
Procedure for the Three-Component Reaction
Into an
oven-dried flask, N,N-dimethylaniline
(1a, 242 mg, 2.0 mmol), 1-(isocyanomethylsulfonyl)-4-methylbenzene (2a, 195 mg, 1.0 mmol), CuCl (10 mg, 0.1
mmol), Ph3P (26 mg, 0.1 mmol), and TBHP (70% aq,
2.4 mmol) were added at r.t.. Under the protection of N2,
MeCN (5 mL) was added, and the reaction mixture was allowed to react
at 80 ˚C for 6 h. After the end of the reaction,
the mixture was filtered through a pad of Celite, and the filtrate
was concentrated until the solvent was completely removed. The residue
was then separated on a silica gel column, and the final product was
obtained as a yellow powder (190 mg, 57%). ¹H
NMR (400 MHz, CDCl3, TMS): δ = 7.72
(d, J = 8.8
Hz, 2 H), 7.29-7.35 (m, 3 H), 7.27 (m, 1 H), 6.89 (t, J = 7.4 Hz,
1 H), 6.68 (d, J = 7.6
Hz, 2 H), 4.69 (d, J = 7.2
Hz, 2 H), 3.75 (s, 2 H), 2.99 (s, 3 H), 2.46 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 170.4, 149.0,
145.6, 133.7, 130.0, 129.5, 128.9, 119.3, 113.4, 59.8, 58.6, 40.1,
21.8. HRMS (EI): m/z calcd for
C17H20N2O3S [M]+:
332.1195; found: 332.1186.