Enantioselective LaIII-pyBOX-Catalyzed Nitro-Michael Addition to (E)-2-Azachalcones

A [La(OTf)3] complex with a new pyBOX ligand bearing a bulky 1-naphthylmethyl substituent at the 4-position of the oxazoline ring catalyzes the conjugate addition of nitroalkanes to a broad range of (E)-2-azachalcones, providing the expected nitro-Michael products with good yields and enanItiomeric excesses up to 87%. The optical purity of the products can be increased by a single crystallization. A plausible stereochemical model to account for the observed stereochemistry has been proposed.Financial support from the Ministerio de Ciencia e Innovacion (MICINN) and Fundo Europeu de Desenvolvimento Regional (FEDER) (grant number CTQ2009-13083) and from Generalitat Valenciana (grant numbers ACOMP/2012/212 and ISIC 2012/001) is acknowledged.Blay Llinares, G.; Incerti, C.; Muñoz Roca, MDC.; Pedro Llinares, JR. (2013). Enantioselective LaIII-pyBOX-Catalyzed Nitro-Michael Addition to (E)-2-Azachalcones. European Journal of Organic Chemistry. 1696-1705. https://doi.org/10.1002/ejoc.20120157916961705P. Perlmutter Conjugate Addition Reactions in Organic Synthesis Pergamon Oxford 1992Alexakis, A. (s. f.). The Conjugate Addition Reaction. Transition Metals for Organic Synthesis, 553-562. doi:10.1002/9783527619405.ch3hCsákÿ, A. G., Herrán, G. de la, & Murcia, M. C. (2010). Conjugate addition reactions of carbon nucleophiles to electron-deficient dienes. Chemical Society Reviews, 39(11), 4080. doi:10.1039/b924486gde Vries (Ed.). (2011). Conjugate Addition Reactions. Stereoselective Synthesis 1. doi:10.1055/sos-sd-201-00304Howell, G. P. (2012). Asymmetric and Diastereoselective Conjugate Addition Reactions: C–C Bond Formation at Large Scale. Organic Process Research & Development, 16(7), 1258-1272. doi:10.1021/op200381wOno, N. (2001). The Nitro Group in Organic Synthesis. Wiley Series in Organic Nitro Chemistry. doi:10.1002/0471224480Halland, N., Hazell, R. G., & Jørgensen, K. A. (2002). Organocatalytic Asymmetric Conjugate Addition of Nitroalkanes to α,β-Unsaturated Enones Using Novel Imidazoline Catalysts. The Journal of Organic Chemistry, 67(24), 8331-8338. doi:10.1021/jo0261449García Mancheño, O., Tangen, P., Rohlmann, R., Fröhlich, R., & Alemán, J. (2010). Synthesis of Chiral Cyclic Nitrones by Asymmetric Addition of β-Ketosulfones to Nitroalkenes followed by Reductive Cyclization. Chemistry - A European Journal, 17(3), 984-992. doi:10.1002/chem.201001914Sil, D., Sharon, A., Maulik, P. R., & Ram, V. J. (2004). A concise synthesis of highly functionalized α,β-unsaturated γ-butyrolactones through ring contraction of 2H-pyran-2-ones. Tetrahedron Letters, 45(33), 6273-6276. doi:10.1016/j.tetlet.2004.06.093Blay, G., Hernández-Olmos, V., & Pedro, J. R. (2010). Enantioselective Henry Addition of Methyl 4-Nitrobutyrate to Aldehydes. Chiral Building Blocks for 2-Pyrrolidinones and Other Derivatives. Organic Letters, 12(13), 3058-3061. doi:10.1021/ol1010888Ballini, R., Barboni, L., Bosica, G., & Fiorini, D. (2002). One-Pot Synthesis of γ-Diketones, γ-Keto Esters, and Conjugated Cyclopentenones­ from Nitroalkanes. Synthesis, (18), 2725-2728. doi:10.1055/s-2002-35993Zhu, S., Yu, S., & Ma, D. (2008). Highly Efficient Catalytic System for Enantioselective Michael Addition of Aldehydes to Nitroalkenes in Water. Angewandte Chemie, 120(3), 555-558. doi:10.1002/ange.200704161Ballini, R., Bosica, G., Fiorini, D., Palmieri, A., & Petrini, M. (2005). Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes: Recent Results. Chemical Reviews, 105(3), 933-972. doi:10.1021/cr040602rHanessian, S., & Pham, V. (2000). Catalytic Asymmetric Conjugate Addition of Nitroalkanes to Cycloalkenones. Organic Letters, 2(19), 2975-2978. doi:10.1021/ol000170gHanessian, S., Shao, Z., & Warrier, J. S. (2006). Optimization of the Catalytic Asymmetric Addition of Nitroalkanes to Cyclic Enones withtrans-4,5-Methano-l-proline. Organic Letters, 8(21), 4787-4790. doi:10.1021/ol0618407Mitchell, C. E. T., Brenner, S. E., García-Fortanet, J., & Ley, S. V. (2006). An efficient, asymmetric organocatalyst-mediated conjugate addition of nitroalkanes to unsaturated cyclic and acyclic ketones. Org. Biomol. Chem., 4(10), 2039-2049. doi:10.1039/b601877gPrieto, A., Halland, N., & Jørgensen, K. A. (2005). Novel Imidazolidine-Tetrazole Organocatalyst for Asymmetric Conjugate Addition of Nitroalkanes. Organic Letters, 7(18), 3897-3900. doi:10.1021/ol051301mGotoh, H., Ishikawa, H., & Hayashi, Y. (2007). Diphenylprolinol Silyl Ether as Catalyst of an Asymmetric, Catalytic, and Direct Michael Reaction of Nitroalkanes with α,β-Unsaturated Aldehydes. Organic Letters, 9(25), 5307-5309. doi:10.1021/ol702545zHojabri, L., Hartikka, A., Moghaddam, F. M., & Arvidsson, P. I. (2007). A New Imidazole-Containing Imidazolidinone Catalyst for Organocatalyzed Asymmetric Conjugate Addition of Nitroalkanes to Aldehydes. Advanced Synthesis & Catalysis, 349(4-5), 740-748. doi:10.1002/adsc.200600316Zu, L., Xie, H., Li, H., Wang, J., & Wang, W. (2007). Highly Enantioselective Organocatalytic Conjugate Addition of Nitromethane to α,β-Unsaturated Aldehydes: Three-Step Synthesis of Optically Active Baclofen. Advanced Synthesis & Catalysis, 349(17-18), 2660-2664. doi:10.1002/adsc.200700353Wang, Y., Li, P., Liang, X., Zhang, T. Y., & Ye, J. (2008). An efficient enantioselective method for asymmetric Michael addition of nitroalkanes to α,β-unsaturated aldehydes. Chemical Communications, (10), 1232. doi:10.1039/b717000aYang, Y.-Q., Chen, X.-K., Xiao, H., Liu, W., & Zhao, G. (2010). Organocatalyzed enantioselective Michael additions of nitroalkanes to enones by using primary–secondary diamine catalysts. Chemical Communications, 46(23), 4130. doi:10.1039/c002552fLiu, C., & Lu, Y. (2010). Primary Amine/(+)-CSA Salt-Promoted Organocatalytic Conjugate Addition of Nitro Esters to Enones. Organic Letters, 12(10), 2278-2281. doi:10.1021/ol1006407Kwiatkowski, P., Dudziński, K., & Łyżwa, D. (2011). Effect of High Pressure on the Organocatalytic Asymmetric Michael Reaction: Highly Enantioselective Synthesis of γ-Nitroketones with Quaternary Stereogenic Centers. Organic Letters, 13(14), 3624-3627. doi:10.1021/ol201275hKim, D. Y., & Huh, S. C. (2001). Enantioselective Michael reaction of nitroalkanes and chalcones by phase-transfer catalysis using chiral quaternary ammonium salts. Tetrahedron, 57(43), 8933-8938. doi:10.1016/s0040-4020(01)00891-2Bakó, T., Bakó, P., Szöllõsy, Á., Czugler, M., Keglevich, G., & Tõke, L. (2002). Enantioselective Michael reaction of 2-nitropropane with substituted chalcones catalysed by chiral azacrown ethers derived from α-d-glucose. Tetrahedron: Asymmetry, 13(2), 203-209. doi:10.1016/s0957-4166(02)00068-xAllingham, M. T., Howard-Jones, A., Murphy, P. J., Thomas, D. A., & Caulkett, P. W. R. (2003). Synthesis and applications of C2-symmetric guanidine bases. Tetrahedron Letters, 44(48), 8677-8680. doi:10.1016/j.tetlet.2003.09.162Corey, E. J., & Zhang, F.-Y. (2000). Enantioselective Michael Addition of Nitromethane to α,β-Enones Catalyzed by Chiral Quaternary Ammonium Salts. A Simple Synthesis of (R)-Baclofen. Organic Letters, 2(26), 4257-4259. doi:10.1021/ol0068344Arai, S., Nakayama, K., Ishida, T., & Shioiri, T. (1999). Asymmetric cyclopropanation reaction Under phase-transfer catalyzed conditions. Tetrahedron Letters, 40(22), 4215-4218. doi:10.1016/s0040-4039(99)00679-6Ooi, T., Fujioka, S., & Maruoka, K. (2004). Highly Enantioselective Conjugate Addition of Nitroalkanes to Alkylidenemalonates Using Efficient Phase-Transfer Catalysis ofN-Spiro Chiral Ammonium Bromides. Journal of the American Chemical Society, 126(38), 11790-11791. doi:10.1021/ja047047vOoi, T., Takada, S., Fujioka, S., & Maruoka, K. (2005). N-Spiro Chiral Quaternary Ammonium Bromide Catalyzed Diastereo- and Enantioselective Conjugate Addition of Nitroalkanes to Cyclic α,β-Unsaturated Ketones under Phase-Transfer Conditions. Organic Letters, 7(23), 5143-5146. doi:10.1021/ol0517170Ooi, T., Doda, K., & Maruoka, K. (2003). Highly Enantioselective Michael Addition of Silyl Nitronates to α,β-Unsaturated Aldehydes Catalyzed by Designer Chiral Ammonium Bifluorides: Efficient Access to Optically Active γ-Nitro Aldehydes and Their Enol Silyl Ethers. Journal of the American Chemical Society, 125(30), 9022-9023. doi:10.1021/ja0352810Ooi, T., Takada, S., Doda, K., & Maruoka, K. (2006). Highly Diastereo- and Enantioselective Formal Conjugate Addition of Nitroalkanes to Nitroalkenes by Chiral Ammonium Bifluoride Catalysis. Angewandte Chemie, 118(45), 7768-7770. doi:10.1002/ange.200602787Baschieri, A., Bernardi, L., Ricci, A., Suresh, S., & Adamo, M. â A. (2009). Catalytic Asymmetric Conjugate Addition of Nitroalkanes to 4-Nitro-5-styrylisoxazoles. Angewandte Chemie, 121(49), 9506-9509. doi:10.1002/ange.200905018Hua, M.-Q., Cui, H.-F., Wang, L., Nie, J., & Ma, J.-A. (2010). Reversal of Enantioselectivity by Tuning the Conformational Flexibility of Phase-Transfer Catalysts. Angewandte Chemie, 122(15), 2832-2836. doi:10.1002/ange.200906814Davis, A. P., & Dempsey, K. J. (1995). Synthesis and investigation of a hindered, chiral, bicyclic guanidine. Tetrahedron: Asymmetry, 6(11), 2829-2840. doi:10.1016/0957-4166(95)00374-xWang, J., Li, H., Zu, L., Jiang, W., & Wang, W. (2006). Organocatalytic, Enantioselective Conjugate Addition of Nitroalkanes to Nitroolefins. Advanced Synthesis & Catalysis, 348(15), 2047-2050. doi:10.1002/adsc.200600247Vakulya, B., Varga, S., Csámpai, A., & Soós, T. (2005). Highly Enantioselective Conjugate Addition of Nitromethane to Chalcones Using Bifunctional Cinchona Organocatalysts. Organic Letters, 7(10), 1967-1969. doi:10.1021/ol050431sVakulya, B., Varga, S., & Soós, T. (2008). Epi-Cinchona Based Thiourea Organocatalyst Family as an Efficient Asymmetric Michael Addition Promoter: Enantioselective Conjugate Addition of Nitroalkanes to Chalcones and α,β-UnsaturatedN-Acylpyrroles. The Journal of Organic Chemistry, 73(9), 3475-3480. doi:10.1021/jo702692aLi, P., Wang, Y., Liang, X., & Ye, J. (2008). Asymmetric multifunctional organocatalytic Michael addition of nitroalkanes to α,β-unsaturated ketones. Chemical Communications, (28), 3302. doi:10.1039/b804540bRabalakos, C., & Wulff, W. D. (2008). Enantioselective Organocatalytic Direct Michael Addition of Nitroalkanes to Nitroalkenes Promoted by a Unique Bifunctional DMAP-Thiourea. Journal of the American Chemical Society, 130(41), 13524-13525. doi:10.1021/ja805390kDong, X.-Q., Teng, H.-L., & Wang, C.-J. (2009). Highly Enantioselective Direct Michael Addition of Nitroalkanes to Nitroalkenes Catalyzed by Amine−Thiourea Bearing Multiple Hydrogen-Bonding Donors. Organic Letters, 11(6), 1265-1268. doi:10.1021/ol900025bJiang, X., Zhang, Y., Chan, A. S. C., & Wang, R. (2009). Highly Enantioselective Synthesis of γ-Nitro Heteroaromatic Ketones in a Doubly Stereocontrolled Manner Catalyzed by Bifunctional Thiourea Catalysts Based on Dehydroabietic Amine: A Doubly Stereocontrolled Approach to Pyrrolidine Carboxylic Acids. Organic Letters, 11(1), 153-156. doi:10.1021/ol8025268Lu, H.-H., Wang, X.-F., Yao, C.-J., Zhang, J.-M., Wu, H., & Xiao, W.-J. (2009). Highly enantioselective organocatalytic Michael addition of nitroalkanes to 4-oxo-enoates. Chemical Communications, (28), 4251. doi:10.1039/b905033gMei, K., Jin, M., Zhang, S., Li, P., Liu, W., Chen, X., … Wang, W. (2009). Simple Cyclohexanediamine-Derived Primary Amine Thiourea Catalyzed Highly Enantioselective Conjugate Addition of Nitroalkanes to Enones. Organic Letters, 11(13), 2864-2867. doi:10.1021/ol9010322Yang, W., & Du, D.-M. (2010). Highly Enantioselective Michael Addition of Nitroalkanes to Chalcones Using Chiral Squaramides as Hydrogen Bonding Organocatalysts. Organic Letters, 12(23), 5450-5453. doi:10.1021/ol102294gManzano, R., Andrés, J. M., Álvarez, R., Muruzábal, M. D., de Lera, Á. R., & Pedrosa, R. (2011). Enantioselective Conjugate Addition of Nitro Compounds to α,β-Unsaturated Ketones: An Experimental and Computational Study. Chemistry - A European Journal, 17(21), 5931-5938. doi:10.1002/chem.201100241Keller, E., Veldman, N., Spek, A. L., & Feringa, B. L. (1997). Catalytic enantioselective Michael addition reactions of α-nitroesters to α,β-unsaturated ketones. Tetrahedron: Asymmetry, 8(20), 3403-3413. doi:10.1016/s0957-4166(97)00432-1Funabashi, K., Saida, Y., Kanai, M., Arai, T., Sasai, H., & Shibasaki, M. (1998). Catalytic asymmetric Michael addition of nitromethane to enones controlled by (R)-LPB. Tetrahedron Letters, 39(41), 7557-7558. doi:10.1016/s0040-4039(98)01644-xTaylor, M. S., Zalatan, D. N., Lerchner, A. M., & Jacobsen, E. N. (2005). Highly Enantioselective Conjugate Additions to α,β-Unsaturated Ketones Catalyzed by a (Salen)Al Complex. Journal of the American Chemical Society, 127(4), 1313-1317. doi:10.1021/ja044999sPalomo, C., Pazos, R., Oiarbide, M., & García, J. M. (2006). Catalytic Enantioselective Conjugate Addition of Nitromethane to α′-Hydroxy Enones as Surrogates of α,β-Unsaturated Carboxylic Acids and Aldehydes. Advanced Synthesis & Catalysis, 348(10-11), 1161-1164. doi:10.1002/adsc.200606076Wang, L., Zhang, Q., Zhou, X., Liu, X., Lin, L., Qin, B., & Feng, X. (2010). Asymmetric Conjugate Addition of Nitromethane to Enones Catalyzed by Chiral N,N′-Dioxide-Scandium(III) Complexes. Chemistry - A European Journal, 16(26), 7696-7699. doi:10.1002/chem.201000688(s. f.). doi:10.1021/ja027313Lu, S.-F., Du, D.-M., Xu, J., & Zhang, S.-W. (2006). Asymmetric Michael Addition of Nitroalkanes to Nitroalkenes Catalyzed byC2-Symmetric Tridentate Bis(oxazoline) and Bis(thiazoline) Zinc Complexes. Journal of the American Chemical Society, 128(23), 7418-7419. doi:10.1021/ja0604008Yang, X., Zhou, X., Lin, L., Chang, L., Liu, X., & Feng, X. (2008). Highly Enantioselective Direct Michael Addition of Nitroalkanes to Nitroolefins Catalyzed by La(OTf)3/N,N′-Dioxide Complexes. Angewandte Chemie, 120(37), 7187-7189. doi:10.1002/ange.200802285Ogawa, T., Mouri, S., Yazaki, R., Kumagai, N., & Shibasaki, M. (2011). Intermediate as Catalyst: Catalytic Asymmetric Conjugate Addition of Nitroalkanes to α,β-Unsaturated Thioamides. Organic Letters, 14(1), 110-113. doi:10.1021/ol202898eTaylor, M. S., & Jacobsen, E. N. (2003). Enantioselective Michael Additions to α,β-Unsaturated Imides Catalyzed by a Salen−Al Complex. Journal of the American Chemical Society, 125(37), 11204-11205. doi:10.1021/ja037177oGreiner-Bechert, L., Sprang, T., & Otto, H.-H. (2005). Reactions of Heteroaryl Substituted Propenones. Monatshefte f�r Chemie - Chemical Monthly, 136(4), 635-653. doi:10.1007/s00706-004-0265-8Molleti, N., Rana, N. K., & Singh, V. K. (2012). Highly Enantioselective Conjugate Addition of Malononitrile to 2-Enoylpyridines with Bifunctional Organocatalyst. Organic Letters, 14(17), 4322-4325. doi:10.1021/ol3015607Boersma, A. J., de Bruin, B., Feringa, B. L., & Roelfes, G. (2012). Ligand denticity controls enantiomeric preference in DNA-based asymmetric catalysis. Chemical Communications, 48(18), 2394. doi:10.1039/c2cc17350fHua, M.-Q., Wang, L., Cui, H.-F., Nie, J., Zhang, X.-L., & Ma, J.-A. (2011). A powerful synergistic effect for highly efficient diastereo- and enantioselective phase-transfer catalyzed conjugate additions. Chem. Commun., 47(5), 1631-1633. doi:10.1039/c0cc04321dEvans, D. A., Fandrick, K. R., Song, H.-J., Scheidt, K. A., & Xu, R. (2007). Enantioselective Friedel−Crafts Alkylations Catalyzed by Bis(oxazolinyl)pyridine−Scandium(III) Triflate Complexes. Journal of the American Chemical Society, 129(32), 10029-10041. doi:10.1021/ja072976iReetz, M. T., & Jiao, N. (2006). Copper–Phthalocyanine Conjugates of Serum Albumins as Enantioselective Catalysts in Diels–Alder Reactions. Angewandte Chemie, 118(15), 2476-2479. doi:10.1002/ange.200504561Matsumoto, K., Jitsukawa, K., & Masuda, H. (2005). Preparation of new bis(oxazoline) ligand bearing non-covalent interaction sites and an application in the highly asymmetric Diels–Alder reaction. Tetrahedron Letters, 46(34), 5687-5690. doi:10.1016/j.tetlet.2005.06.108Otto, S., & Engberts, J. B. F. N. (1999). A Systematic Study of Ligand Effects on a Lewis-Acid-Catalyzed Diels−Alder Reaction in Water. Water-Enhanced Enantioselectivity. Journal of the American Chemical Society, 121(29), 6798-6806. doi:10.1021/ja984273uRay, S. K., Singh, P. K., & Singh, V. K. (2011). Enantioselective Michael Addition of Malonates to 2-EnoylpyridineN-Oxides Catalyzed by Chiral Bisoxazoline–Zn(II) Complex. Organic Letters, 13(21), 5812-5815. doi:10.1021/ol202405vSingh, P. K., & Singh, V. K. (2010). Enantioselective Friedel−Crafts Alkylation of Pyrroles Catalyzed by PYBOX-DIPH-Zn(II) Complexes. Organic Letters, 12(1), 80-83. doi:10.1021/ol902360bBarroso, S., Blay, G., & Pedro, J. R. (2007). 2-Alkenoyl PyridineN-Oxides, Highly Efficient Dienophiles for the Enantioselective Cu(II)−Bis(oxazoline) Catalyzed Diels−Alder Reaction†. Organic Letters, 9(10), 1983-1986. doi:10.1021/ol0705752Barroso, S., Blay, G., Muñoz, M. C., & Pedro, J. R. (2008). Highly Enantio- and Diastereoselective Inverse Electron Demand Hetero-Diels-Alder Reaction using 2-Alkenoylpyridine N-Oxides as Oxo-Heterodienes. Advanced Synthesis & Catalysis, 351(1-2), 107-111. doi:10.1002/adsc.200800606Barroso, S., Blay, G., Muñoz, M. C., & Pedro, J. R. (2011). Highly Enantioselective Nitrone Cycloadditions with 2-Alkenoyl PyridineN-Oxides Catalyzed by Cu(II)−BOX Complexes. Organic Letters, 13(3), 402-405. doi:10.1021/ol102716eLivieri, A., Boiocchi, M., Desimoni, G., & Faita, G. (2010). Enantioselective Cycloadditions of 2-Alkenoylpyridine-N-oxides Catalysed by a Bis(oxazoline)/CuII Complex: Structure of the Reactive Intermediate. Chemistry - A European Journal, 17(2), 516-520. doi:10.1002/chem.201002017Kingsbury, C. A. (1998). D/H Exchange in Nitro Diastereomers. The Journal of Organic Chemistry, 63(12), 3838-3846. doi:10.1021/jo9717402www.ccdc.cam.ac.uk/data_request/cifS 2 6 7 2m RDesimoni, G., Faita, G., Guala, M., Laurenti, A., & Mella, M. (2005). A New Pyridine-2,6-bis(oxazoline) for Efficient and Flexible Lanthanide-Based Catalysts of Enantioselective Reactions with 3-Alkenoyl-2-oxazolidinones. Chemistry - A European Journal, 11(13), 3816-3824. doi:10.1002/chem.200401213Desimoni, G., Faita, G., Piccinini, F., & Toscanini, M. (2006). Enantioselective Mukaiyama-Aldol Reaction of Pyruvates and 1-Phenyl- 1-trimethylsilyloxyethene Catalyzed by Lanthanide/Pybox Complexes. European Journal of Organic Chemistry, 2006(23), 5228-5230. doi:10.1002/ejoc.200600716III S S [21b] III pyBOX-5 IIIHovinen, J., & Hakala, H. (2001). Versatile Strategy for Oligonucleotide Derivatization. Introduction of Lanthanide(III) Chelates to Oligonucleotides. Organic Letters, 3(16), 2473-2476. doi:10.1021/ol016093mAlexander, R., Balasundaram, A., Batchelor, M., Brookings, D., Crépy, K., Crabbe, T., … Wright, S. (2008). 4-(1,3-Thiazol-2-yl)morpholine derivatives as inhibitors of phosphoinositide 3-kinase. Bioorganic & Medicinal Chemistry Letters, 18(15), 4316-4320. doi:10.1016/j.bmcl.2008.06.076Phillips, A. J., Uto, Y., Wipf, P., Reno, M. J., & Williams, D. R. (2000). Synthesis of Functionalized Oxazolines and Oxazoles with DAST and Deoxo-Fluor. Organic Letters, 2(8), 1165-1168. doi:10.1021/ol005777