CAN-Catalyzed Vinylogous Povarov Reactions: The First Three-Component Synthesis of 2-Functionalized Tetrahydroquinolines from Anilines, ­Cinnamaldehyde and Vinyl Ethers

Abstract

The CAN-catalyzed reaction between anilines, cinnam­aldehyde and vinyl ethers affords 2-styryl-1,2,3,4-tetrahydroquinolines. In the case of noncyclic vinyl ethers, these reactions are completely stereoselective and furnish exclusively the diastereomer with a cis relationship between the styryl and alkoxy groups.

cycloadditions - multicomponent reactions - stereo­selective synthesis - Lewis acids - quinolines

References and Notes

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13a

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17

Representative Procedure
An equimolecular (3 mmol) mixture of aniline and cinnamaldehyde was dissolved in MeCN (20 mL). To this stirred solution, ethyl vinyl ether (4.5 mmol) and 5 mol% of CAN were added, and stirring was continued for 3 h. After completion of the reaction, as indicated by TLC (2 h reaction time), the mixture was poured into H₂O (20 mL) and extracted with CH₂Cl₂ (3 × 20 mL). The combined extracts were dried over anhyd Na₂SO₄ and evaporated, and the residue was purified by silica gel column chromatography using a PE-EtOAc mixture (96:4), to afford 60% of a mixture of compounds 4a and 5a in 57:43 ratio, as determined by ¹H NMR analysis. Analytical samples of compounds 4a and 5a were obtained through a second column chromatography.
Data for 4a: viscous oil. IR (neat) 3327.2, 3024.0, 2875.2, 1609.3, 1484.2, 1364.6, 1259.6, 1063.4 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.03-2.22 (m, 2 H), 2.73-2.84 (m, 1 H), 3.82-3.88 (m, 3 H), 4.19 (dd, J = 7.8, 3.5 Hz, 1 H), 5.13 (d, J = 7.3 Hz, 1 H), 6.35 (dd, J = 15.8, 7.8 Hz, 1 H), 6.61-6.71 (m, 2 H), 6.85 (td, J = 7.5, 0.9 Hz, 1 H), 7.14 (td, J = 7.5, 0.9 Hz, 1 H), 7.27-7.47 (m, 6 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 26.1, 43.1, 56.2, 66.9, 75.9, 115.4, 119.4, 122.3, 126.9, 128.3, 129.0, 129.2, 130.2, 130.8, 131.8, 137.1, 144.7. Anal. Calcd for C₁₉H₁₉NO: C, 82.28; H, 6.90; N, 5.05. Found: C, 82.03; H, 6.65; N, 4.89.
Data for 5a: viscous oil. IR (neat): 3333.8, 3024.6, 2861.3, 1611.3, 1482.8, 1363.1, 1264.0, 1127.0, 1042.2 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.91-2.01 (m, 1 H), 2.20-2.35 (m, 2 H), 3.48 (dd, J = 9.7, 8.9 Hz, 1 H), 3.84-3.94 (m, 1 H), 4.01-4.11 (m, 2 H), 4.64 (d, J = 4.8 Hz, 1 H), 6.24 (dd, J = 15.8, 8.5 Hz, 1 H), 6.67-6.73 (m, 2 H), 6.84 (td, J = 7.4, 0.8 Hz, 1 H), 7.17 (td, J = 7.4, 0.8 Hz, 1 H), 7.28-7.49 (m, 6 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 29.4, 41.9, 56.3, 65.7, 76.2, 115.4, 118.9, 120.6, 127.0, 128.5, 129.2, 129.5, 130.2, 131.7, 133.9, 136.8, 145.2. Anal. Calcd for C₁₉H₁₉NO: C, 82.28; H, 6.90; N, 5.05. Found: C, 81.97; H, 6.78; N, 4.89.

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18j

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20g Ko S. Yao CF. Tetrahedron  2006,  62:  7293 

20h Sridharan V. Avendaño C. Menéndez JC. Tetrahedron  2007,  63:  673 

21 Shanmugam P. Perumal PT. Tetrahedron  2006,  62:  9726 

22 Markó IE. Ates A. Gautier A. Leroy B. Plancher J.-M. Quesnel Y. Vanherck J.-C. Angew. Chem. Int. Ed.  1999,  12:  2653