Povarov Reaction Zain Yousaf 10/22/2013 University of Illinois at Urbana-Champaign
Contents Introduction Chiral Lewis Acids Bronsted Acid Lanthanide complexes L-ramipril acid derived Sulfonamide Urea Derivative Chiral Phosphoric Acid derivatievs
Povarov Reaction Povarov and Mikhailov in 1963 L. S. Povarov and B. M. Mikhailov, Izv. Akad. Nauk. SSSR, Ser. Khim., 1963, 953 954; L.S.Povarov, V.I.Grigos, and B.M.Mikhailov, Izv.Akad. 51. Nauk SSSR, Otd.Khim.Nauk, 2039(1963).
Applications Chem. Rev. 2011, 111, 7157 7259
Mechanism Stepwise or concerted Chem. Rev. 2011, 111, 7157 7259
Stepwise Trapping intermediates. 92:8-97:3 dr Sridharan, V.; Avenda~no, C.; Menendez, J. C. Synthesis 2008, 7, 1039.
Diastereoselectivity Sridharan, V.; Avenda~no, C.; Menendez, J. C. Synthesis 2008, 7, 1039.
Chiral Auxiliary Prato, 1989 Borrione. E; Prato, M; Scorrano, G; Stivanello, M. J. CHEM. SOC. PERKIN TRANS. I 1989, 2245
Catalytic Chiral Lewis Acid Kobayashi, 1996 H. Ishitani and S. Kobayashi, Tetrahedron Lett., 1996, 37, 7357 7360.
Transition State Kobayashi, 1996 Si H. Ishitani and S. Kobayashi, Tetrahedron Lett., 1996, 37, 7357 7360.
Avoiding the OH moity Sundararajan, 2001 G. Sundararajan, N. Prabagaran and B. Varghese, Org. Lett., 2001, 3, 1973 1976.
Rationalizing ee G. Sundararajan, N. Prabagaran and B. Varghese, Org. Lett., 2001, 3, 1973 1976.
Efficient chiral Lewis Acids Feng, 2010 M. Xie, X. Chen, Y. Zhu, B. Gao, L. Lin, X. Liu and X. Feng, Angew. Chem., Int. Ed., 2010, 49, 3799 3802
Quaternary stereocenter at C4 Feng, 2011 M. Xie, X. Liu, Y. Zhu, X. Zhao, Y. Xia, L. Lin and X. Feng, Chem. Eur. J., 2011, 17, 13800 13805.
Chiral Bronsted Acid Akiyama 2006 T. Akiyama, H. Morita and K. Fuchibe, J. Am. Chem. Soc., 2006, 128, 13070 13071
Enecarbamates And Si face Attack Masson and Zhu 2009 4 steps 32% overall yield H. Liu, G. Dagousset, G. Masson, P. Retailleau and J. Zhu, J. Am. Chem. Soc., 2009, 131, 4598 4599
Difference is Stereoselectivity H. Liu, G. Dagousset, G. Masson, P. Retailleau and J. Zhu, J. Am. Chem. Soc., 2009, 131, 4598 4599
Tri Substituted Quinolines Masson and Zhu 2011 G. Dagousset, J. Zhu and G. Masson, J. Am. Chem. Soc., 2011, 133, 14804 14813
Tri Substituted Quinolines G. Dagousset, J. Zhu and G. Masson, J. Am. Chem. Soc., 2011, 133, 14804 14813
Sulfonamide Urea Derivative Jacobson 2010 A. H. Xu, S. J. Zuend, M. G. Woll, Y. Tao and E. N. Jacobsen, Science, 2010, 327, 986 990.
Sulfonamide Urea Derivative A. H. Xu, S. J. Zuend, M. G. Woll, Y. Tao and E. N. Jacobsen, Science, 2010, 327, 986 990.
Group Question Figure out if the mechanism is concerted or stepwise using the following infomation? Kinetic isotope effect on hydrogen ortho to aniline is 0.92. Hammet correlation obtained using aniline substituent ρ = +1.96 A. H. Xu, S. J. Zuend, M. G. Woll, Y. Tao and E. N. Jacobsen, Science, 2010, 327, 986 990.
Group Answer No primary kinetic isotope effect mean aromatization is fast so d is not part of rate limiting step. Positive hammet correlation consistent with a and c but not b. Small kinetic isotope effect mean rehybradization is part of rate limiting step thus c. A. H. Xu, S. J. Zuend, M. G. Woll, Y. Tao and E. N. Jacobsen, Science, 2010, 327, 986 990.
Vinyl Indoles as dienophiles Bernadi and Ricci 2010 G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi and A. Ricci, Chem. Commun., 2010, 46, 327 329.
3-Vinyl Indoles 3-Vinyl indole G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi and A. Ricci, Chem. Commun., 2010, 46, 327 329.
2-Vinyl Indoles 2-Vinyl indole G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi and A. Ricci, Chem. Commun., 2010, 46, 327 329.
Cyclic tertiary Enethioureas Masson and Zhu 2012 G. Dagousset, P. Retailleau, G. Masson and J. Zhu, Chem. Eur. J., 2012, 18, 5869 5873.
Cyclic tertiary Enethioureas G. Dagousset, P. Retailleau, G. Masson and J. Zhu, Chem. Eur. J., 2012, 18, 5869 5873.
Tri substituted quinolines Masson 2012 L. He, M. Bekkaye, P. Retailleau and G. Masson, Org. Lett., 2012, 14, 3158 3161.
Quaternary stereocenter at C4 Luo and Gong 2012 F. Shi, G.-J. Xing, Z.-L. Tao, S.-W. Luo, S.-J. Tu and L.-Z. Gong, J. Org. Chem., 2012, 77, 6970 6979.
Quaternary stereocenter at C4 F. Shi, G.-J. Xing, Z.-L. Tao, S.-W. Luo, S.-J. Tu and L.-Z. Gong, J. Org. Chem., 2012, 77, 6970 6979.
Conclusion Povarov reaction is efficient and highly stereoselective method of constructing 2 to 3 substituted quinolones with large functional group tolerance. 3 different comonents can be fused together in a single step. Can be scaled up with reduction in catalyst loading but usually at the cost of stereoselectivity. Electron rich dienophiles and electron poor anilines and aldehydes necessary to get good yields. Still low yields and ee with aliphatic aldehydes.
References Chem. Soc. Rev., 2013, 42, 902 923 Chem. Rev. 2011, 111, 7157 7259 Synthesis. 1993, 535. Russ. Chem. Rev. 1967, 36, 656. Sridharan, V.; Avenda~no, C.; Menendez, J. C. Synthesis 2008, 7, 1039. Borrione. E; Prato, M; Scorrano, G; Stivanello, M. J. CHEM. SOC. PERKIN TRANS. I 1989, 2245 H. Ishitani and S. Kobayashi, Tetrahedron Lett., 1996, 37, 7357 7360. G. Sundararajan, N. Prabagaran and B. Varghese, Org. Lett., 2001, 3, 1973 1976. M. Xie, X. Chen, Y. Zhu, B. Gao, L. Lin, X. Liu and X. Feng, Angew. Chem., Int. Ed., 2010, 49, 3799 3802 M. Xie, X. Liu, Y. Zhu, X. Zhao, Y. Xia, L. Lin and X. Feng, Chem. Eur. J., 2011, 17, 13800 13805. H. Liu, G. Dagousset, G. Masson, P. Retailleau and J. Zhu, J. Am. Chem. Soc., 2009, 131, 4598 4599 G. Dagousset, J. Zhu and G. Masson, J. Am. Chem. Soc., 2011, 133, 14804 14813 A. H. Xu, S. J. Zuend, M. G. Woll, Y. Tao and E. N. Jacobsen, Science, 2010, 327, 986 990. G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi and A. Ricci, Chem. Commun., 2010, 46, 327 329. G. Dagousset, P. Retailleau, G. Masson and J. Zhu, Chem. Eur. J., 2012, 18, 5869 5873. L. He, M. Bekkaye, P. Retailleau and G. Masson, Org. Lett., 2012, 14, 3158 3161. F. Shi, G.-J. Xing, Z.-L. Tao, S.-W. Luo, S.-J. Tu and L.-Z. Gong, J. Org. Chem., 2012, 77, 6970 6979.