Multicomponent Cascade Synthesis of 1,4-Dihydropyridine Derivatives from Pyridines, Methyl Propiolate, and Aromatic Acids

Abstract

A metal-free highly efficient synthesis of a wide range of 4-propenyl 1,4-DHPs from pyridines, methyl propiolate, and aromatic acids is described. The reactions are conducted under convenient conditions and provide products with excellent regioselectivity in good to excellent yields, with broad substrate scope.

Key words

1,4-DHPs - pyridines - methyl propiolate - aromatic acids - multicomponent reactions

• References and Notes

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• 13 General Procedure for the Preparation of (E)-3-Methoxy-2-{1-[(E)-3-methoxy-3- oxoprop-1-en-1-yl]-1,4-dihydropyridin-4-yl}-3-oxoprop-1-en-1-yl benzoate To a solution of pyridine (0.3 mmol) and methyl propiolate (0.72 mmol) in MeCN (1 mL) was added benzoic acid (0.33 mmol) under air atmosphere, and the mixture was stirred at r.t. for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOAc–PE = 1:2) to yield the corresponding product
• 14 Selected Physical and Spectral Data for (E)-3-Methoxy-2-{1-[(E)-3-methoxy-3-oxoprop- 1-en-1-yl]-1,4-dihydropyridin-4-yl}-3-oxoprop-1-en-1-yl benzoate (7a) Yellow amorphous solid; yield: 94 mg (85%). IR (KBr): ν_max = 1743, 1706, 1601, 1228, 1153 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.60 (s, 1 H), 8.07–7.99 (m, 2 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.34–7.25 (m, 2 H), 7.29 (d, J = 13.6 Hz, 1 H), 6.34 (d, J = 7.5 Hz, 2 H), 5.12 (d, J = 13.6 Hz, 1 H), 4.94 (d, J = 4.5 Hz, 2 H), 4.66–4.52 (m, 1 H), 3.80 (s, 3 H, OCH₃), 3.73 (s, 3 H, OCH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 168.8, 167.1, 162.4, 147.2, 144.3, 134.4, 130.5, 130.3, 128.9, 127.8, 119.9, 108.6, 90.0, 89.2, 52.0, 51.1, 51.0, 31.0. ESI-MS: m/z = 370 (100) [M + H⁺]. Anal Calcd for C₂₀H₁₉NO₆: C, 65.03; H, 5.18; N, 3.79. Found: C, 64.86; H, 5.51; N, 3.64