Gold(I)-Catalyzed Oriented Assembly of Dihydropyridines

Abstract

A novel method for the assembly of multisubstitued dihydropyridines has been developed starting from methyl propiolate and propargylamines. The reactions were efficiently catalyzed by AuPPh₃Cl to get high regioselectivity and high yields. And alternatively, since propargylamines could be easily derived by the CuCl-mediated addition of methyl propiolate to imines, the reactions could be carried out as a sequential three-component model.

Key words

triphenylphosphine gold chloride - methyl propiolate - propargylamines - dihydropyridines

• References and Notes

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• 5 Typical Procedure for the Synthesis of Dihydropyridines from Propargylamines In a round-bottomed flask equipped with a magnetic stirring bar, a mixture of 1a (10.0 mmol) and 2 (11.0 mmol), AuPPh₃Cl (0.01 mmol), and Et₃N (0.01 mmol) in DCE (10.0 mL) was heated at 80 °C under inert nitrogen atmosphere until the consumption of 1 was detected by TLC. The mixture was filtered, and the filtration was concentrated to give a residue, which was purified by silica column chromatography to provide 4a as pale yellow solid, 83% yield; mp 51.7–56.5 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.97 (d, J = 0.8 Hz, 1 H), 7.33–7.27 (m, 7 H), 7.14 (t, J = 7.4 Hz, 1 H), 7.06 (d, J = 7.9 Hz, 2 H), 5.91 (d, J = 6.3 Hz, 1 H), 5.63 (d, J = 5.6 Hz, 1 H), 3.79 (s, 3 H), 3.74 (s, 3 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 168.40, 165.57, 144.27, 142.22, 140.77, 129.47, 129.22, 128.32, 127.51, 125.38, 125.14, 119.86, 119.80, 102.55, 61.84, 52.26, 51.30 ppm. HRMS (ES): m/z calcd for C₂₁H₁₉NO₄: 349.1315; found: 349.1314.
• 6 Typical Sequential Synthesis of Dihydropyridines from Imines A mixture of N-benzylideneaniline (10.0 mmol), methyl propiolate (10.0 mmol), and CuCl (1.0 mmol) was heated at 80 °C in DCE solution for about 5 h. After cooling, AuPPh₃Cl (0.01 mmol) and Et₃N (0.01 mmol) were added to the reaction system. The mixture was further stirred at 80 °C under inert nitrogen atmosphere. The reaction was completed within 5 h according to TLC. Conventional processing and purification gave 4a as pale yellow solid in 81% yield.
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