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.

Key words

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

References and Notes

• See, for instance:
• 1a Celing RW. Leeson PD. Moseley AM. Baker R. Foster AC. Grimwood S. Kemp JA. Marshall GR. J. Med. Chem.  1992,  35:  1942 
• 1b Carling RW. Leeson PD. Moseley AM. Smith JD. Saywell K. Trickelbank MD. Kemp JA. Marshall GR. Foster AC. Grimwood S. Bioorg. Med. Chem. Lett.  1993,  3:  65 
• 1c Paris D. Cottin M. Demonchaux P. Augert G. Dupassieux P. Lenoir P. Peck MJ. Jasserand D. J. Med. Chem.  1995,  38:  669 
• 1d Hanada K, Furuya K, Inoguchi K, Miyakawa M, and Nagata N. inventors; WO  0127086.  ; Chem. Abstr. 2001, 134, 295752
• 2a Omura S. Nakagawa A. Hashimoto H. Oiwa R. Iwai Y. Hirano A. Shibukawa N. Kojima Y. J. Antibiot.  1980,  33:  1395 
• 2b Nakagawa A. Iwai Y. Hashimoto H. Miyazaki N. Oiwa R. Takahashi Y. Hirano A. Shibukawa N. Kojima Y. Omura S. J. Antibiot.  1981,  34:  1408 
• 3 Copp BR. Fulton KF. Perry NB. Blunt JW. Munro MHG. J. Org. Chem.  1994,  59:  8233 
• 4 For a review of the chemistry of the martinellines, see: Nyerges M. Heterocycles  2004,  63:  1685 
• 5 For a general review of imino Diels-Alder reactions, see: Buonora P. Olsen J.-C. Oh T. Tetrahedron  2001,  57:  6099 
• 6 For a review of synthetic approaches to 1,2,3,4-tetrahydroquinolines, see: Katritzky AR. Rachwal S. Rachwal B. Tetrahedron  1996,  48:  15031 
• 7 Povarov LS. Russ. Chem. Rev.  1967,  36:  656 
• 8 Kobayashi S. Ishitani H. Nakagawa S. Synthesis  1995,  1195 
• For some representative examples of recent work in this area, see:
• 9a Nagaiah K. Sreenu D. Srinivasa Rao R. Vashishta G. Yadav JS. Tetrahedron Lett.  2006,  47:  4409 
• 9b Srinivas KVNS. Das W. Synlett  2004,  1715 
• 9c Yadav JS. Reddy BVS. Reddy JSS. Srinivasa Rao S. Tetrahedron  2003,  59:  1599 
• 9d Kumar RS. Nagarajan R. Chitra S. Perumal PT. Tetrahedron  2001,  57:  3419 
• 9e Sundararajan G. Prabagaran N. Varghese B. Org. Lett.  2001,  3:  1973 
• 9f Crousse B. Bégué JP. Bonnet-Delpon D. J. Org. Chem.  2000,  65:  5009 
• 10a Hermitage S. Howard JAK. Prichard DJRG. Probert MR. Whiting A. Org. Biomol. Chem.  2004,  2:  2451 
• 10b Alves MJ. Azoia NA. Gil-Fortes A. Tetrahedron  2007,  63:  727 
• 11a Hadden M. Nieuwenhuytzen M. Osborne D. Stevenson PJ. Thompson N. Tetrahedron Lett.  2001,  42:  6417 
• 11b Cia C. Heng L. Ma D. Tetrahedron Lett.  2002,  43:  9405 
• 11c Hadden M. Nieuwenhuyzen M. Osborne D. Stevenson PJ. Thompson N. Walker AD. Tetrahedron  2006,  62:  3977 
• 12 Zhang W. Guo Y. Liu Z. Jin X. Yang L. Liu Z.-L. Tetrahedron  2005,  61:  1325 
• 13a

  For a review, see ref. 5. For some [4+2] cycloadditions of α,β-unsaturated imines leading to 1,4-dihydropyridines, see:

• 13b Barluenga J. Tomás M. López-Pelegrín JA. Rubio E. Tetrahedron Lett.  1997,  38:  3981 
• 13c Ishar MPS. Kumar K. Kaur S. Kumar S. Girdhar NK. Sachar S. Markawa A. Kapoor A. Org. Lett.  2001,  3:  2133 
• 14a Shimizu M. Kurokawa H. Takahashi A. Lett. Org. Chem.  2004,  1:  353 
• 14b Akiyama A. Itoh J. Yokota K. Fuchibe K. Angew. Chem. Int. Ed.  2004,  43:  1566 
• 14c Shimizu M. Kamiya M. Hachiya M. Chem. Lett.  2003,  32:  606 
• 14d Shimizu M. Ogawaand T. Nishi T. Tetrahedron Lett.  2001,  42:  5463 
• 15 Shimizu M. Itohara S. Hase E. Chem. Commun.  2001,  2318 
• 16 Onaka M. Ohno R. Yanagiya N. Izumi Y. Synlett  1993,  141 
• For selected reviews and monographs on multicomponent reactions, see:
• 18a Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 18b Bienaymé H. Hulme C. Oddon G. Schmitt P. Chem. Eur. J.  2000,  6:  3321 
• 18c Ugi A. Pure Appl. Chem.  2001,  73:  187 
• 18d Ugi A. Molecules  2003,  8:  53 
• 18e Orru RVA. de Greef M. Synthesis  2003,  1471 
• 18f Zhu J. Eur. J. Org. Chem.  2003,  1133 
• 18g Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
• 18h Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005. 
• 18i Dömling A. Chem. Rev.  2007,  107:  89 
• 18j

  for a symposium in print on this topic, see: Marek, I., Ed. Tetrahedron 2005, 67, 11299

• Some reviews on CAN-promoted synthetic transformations:
• 19a Nair V. Matthew J. Prabhakaran J. Chem. Soc. Rev.  1997,  127 
• 19b Hwu JR. King K.-Y. Curr. Sci.  2001,  81:  1043 
• 19c Nair V. Panicker SB. Nair LG. George TG. Augustine A. Synlett  2003,  156 
• 19d Nair V. Balagopal L. Rajan R. Mathew J. Acc. Chem. Res.  2004,  37:  21 
• 19e Dhakshinamoorty A. Synlett  2005,  3014 ; Spotlight 143
• Some other CAN-catalyzed reactions have been described very recently. For selected examples, see:
• 20a Zeng X.-F. Ji S.-J. Wang SY. Tetrahedron  2005,  10235 
• 20b Wang SY. Ji S.-J. Tetrahedron  2006,  62:  1527 
• 20c Savitha G. Perumal PT. Tetrahedron Lett.  2006,  47:  3589 
• 20d Nair V. Mohanan K. Suja TD. Suresh E. Tetrahedron Lett.  2006,  47:  705 
• 20e Varala R. Enugala R. Nuvula S. Adapa SR. Synlett  2006,  1009 
• 20f Varala R. Sreelatha N. Adapa SR. Synlett  2006,  1549 
• 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 

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.