Abstract
Achiral benzaldehydes and isocyanides could be transformed enantioselectively
in a Passerini three-component reaction to chiral mandelamides by
using a galacturonic acid derivative as chiral inducer.
Key words
α-hydroxy acid derivative - mandelamide - Passerini reaction - multi-component reaction
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15 A typical experimental procedure is
as follows: A mixture of benzaldehyde (3 ,
6 mmol), 2-(3,4-dimethoxyphenyl)ethyl isocyanide
[12 4 , 6 mmol) and 1,2,3,4-tetra-O -acetyl-α-d -galacturonic
acid
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diluted with CH2 Cl2 , washed with H2 O,
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was taken up in a mixture of 1 N NaOH (5 mL) and dioxane (10 mL).
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2 N HCl and extracted with EtOAc. The combined organic layer was
dried over Na2 SO4 and evaporated. The residue
was purified by flash chromatography on silica gel (EtOAc/hexane
7:3) to obtain colourless crystals of predominantly (S )-N -[2-(3,4-dimethoxyphenyl)ethyl]-2-hydroxy-2-phenylacetamide
(7 , 1.2 g, 3.8 mmol, 63%). 1 H
NMR (300 MHz, CDCl3 ): δ = 2.74
(q, 2 H, NCH2 ), 3.49-3.60 (m, 3 H, PhCH2 ,
OH), 3.83 (s, 3 H, OCH3 ), 3.88 (s, 3 H, OCH3 ),
5.01 (s, 1 H, CHO), 6.06 (br s, 1 H, NH), 6.57-7.39 (m,
8 H, aromatic H). MS (70 eV): m/z = 315
(M+ ), 316 (M+ + 1).
Mp: 91-92 °C (Lit.
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