Catalyst-free three-component synthesis of highly functionalized 2,3-dihydropyrroles
Abstract
An efficient synthesis of fully substituted 2,3-dihydropyrroles has been achieved in one step through the three-component reaction of amines, aromatic aldehydes and α-ketoamides. This atom-economical and catalyst-free reaction is highly stereoselective and generates underexplored heterocycles in a single step. These compounds were examined in an enzymatic assay that led to the identification of potent α-glucosidase inhibitors, thereby demonstrating the utility of this novel methodology in medicinal chemistry.
N-(4-Chlorophenyl)-2-oxopropanamide (3a)
Cl
H
N
O
O
3a
Using 4-chloroaniline (1.0 g, 7.8 mmol), in accordance with General Procedure A, the title
compound 3a was obtained (810 mg, 52% yield) as a white solid.
1H NMR (400 MHz,
CDCl3) δ 8.73 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H).
13C
NMR (100 MHz, CDCl3) δ 197.1, 157.6, 135.0, 130.6, 129.5, 121.1, 24.2. HRMS (ESI-TOF)
m/z calcd. for C9H7NO2Cl-
[M-H]-
: 196.0171, found 196.0170
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