Abstract
The ammonium-tethered pyrrolidine-based organocatalyst catalyzed asymmetric Michael addition/cyclization reaction of α,β-unsaturated aldehydes with 3-hydroxyoxindole in aqueous media was developed, giving the spirooxidole lactones in high yields with high enantioselectivities.
Background: The asymmetric Michael addition/cyclization reaction of 3-hydroxyoxindoles with α,β- unsaturated aldehydes is an important method for the synthesis of chiral spirooxindole derivatives, which are found in a wide range of biologically active natural products and pharmaceutical agents.
Objective: Organocatalyzed asymmetric Michael addition/cyclization reactions are one of the most powerful and effective approaches for the construction of complex molecules from relatively simple starting materials. However, a major problem associated with these organocatalytic system is that high catalyst loading and organic solvents are required. In the present work, our objective was to develop a water-compatible organocatalyst that aimed at lowering catalyst loading and being active in an aqueous system.
Methods: In a typical experiment, To a solution of catalyst 2a (0.008 mmol) and PhCO2H (0.096 mmol) in 0.5 mL of a mixture solvent iPrOH/H2O (1:3) was added α,β-unsaturated aldehyde (0.4 mmol) and 3-hydroxyoxindole (0.8 mmol). The reaction mixture was proceeded at room temperature for 16 hours, and then was extracted with 10 mL dichloromethane to give the cyclized hemiacetal, which was subjected to the direct oxidation with pyridinium chlorochromate (PCC, 1.2 mmol) for 16 hours to give the desired spirooxindole lactones.
Results: The reactions successfully gave spirooxindole lactones in high to excellent yields (81-95%) with moderate to excellent enantioselectivities (up to 99% ee). However, the diastereoselectivities were poor ranging from 1:1.1 to 1:2.3.
Conclusion: The asymmetric Michael addition/cyclization reaction of α,β-unsaturated aldehydes with 3-hydroxyoxindole using ammonium-tethered pyrrolidine-based organocatalyst has been developed. The reaction was performed in aqueous media with low catalyst loading (2 mol%) and provided the spirooxidole lactones in high yields (81-95%) with high enantioselectivities (ee: up to 99%).
Graphical Abstract
[1]
(a) Marti, C.; Carreira, E.M. Construction of spiro[pyrrolidine-3,3′-oxindoles]-recent applications to the synthesis of oxindole alkaloids. Eur. J. Org. Chem., 2003, 2003(12), 2209-2219.
[http://dx.doi.org/10.1002/ejoc.200300050];
(b) Galliford, C.V.; Scheidt, K.A. Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents. Angew. Chem. Int. Ed., 2007, 46(46), 8748-8758.
[http://dx.doi.org/10.1002/anie.200701342] [PMID: 17943924];
(c) Trost, B.; Brennan, M. Asymmetric syntheses of oxindole and indole spirocyclic alkaloid natural products. Synthesis, 2009, 2009(18), 3003-3025.
[http://dx.doi.org/10.1055/s-0029-1216975];
(d) Rana, S.; Blowers, E.C.; Tebbe, C.; Contreras, J.I.; Radhakrishnan, P.; Kizhake, S.; Zhou, T.; Rajule, R.N.; Arnst, J.L.; Munkarah, A.R.; Rattan, R.; Natarajan, A. Isatin derived spirocyclic analogues with α-methylene-γ-butyrolactone as anticancer agents: a structure-activity relationship study. J. Med. Chem., 2016, 59(10), 5121-5127.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00400] [PMID: 27077228];
(e) Eichhorst, A.; Gallhof, M.; Voss, A.; Sekora, A.; Eggers, L.; Huyen, L.T. Spirooxindol-1,3-oxazine alkaloids: Highly potent and selective antitumor agents evolved from iterative structure optimization. In: ChemMedChem; , 2022.
[http://dx.doi.org/10.1002/cmdc.202200162]
[http://dx.doi.org/10.1002/ejoc.200300050];
(b) Galliford, C.V.; Scheidt, K.A. Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents. Angew. Chem. Int. Ed., 2007, 46(46), 8748-8758.
[http://dx.doi.org/10.1002/anie.200701342] [PMID: 17943924];
(c) Trost, B.; Brennan, M. Asymmetric syntheses of oxindole and indole spirocyclic alkaloid natural products. Synthesis, 2009, 2009(18), 3003-3025.
[http://dx.doi.org/10.1055/s-0029-1216975];
(d) Rana, S.; Blowers, E.C.; Tebbe, C.; Contreras, J.I.; Radhakrishnan, P.; Kizhake, S.; Zhou, T.; Rajule, R.N.; Arnst, J.L.; Munkarah, A.R.; Rattan, R.; Natarajan, A. Isatin derived spirocyclic analogues with α-methylene-γ-butyrolactone as anticancer agents: a structure-activity relationship study. J. Med. Chem., 2016, 59(10), 5121-5127.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00400] [PMID: 27077228];
(e) Eichhorst, A.; Gallhof, M.; Voss, A.; Sekora, A.; Eggers, L.; Huyen, L.T. Spirooxindol-1,3-oxazine alkaloids: Highly potent and selective antitumor agents evolved from iterative structure optimization. In: ChemMedChem; , 2022.
[http://dx.doi.org/10.1002/cmdc.202200162]
[2]
(a) Sarkar, S.D.; Biswas, A.; Samanta, R.C.; Studer, A. Catalysis with N-hetercyclic carbenes under oxidative conditions. Chem. Eur. J., 2013, 19, 4664.;
(b) Richter, M.N.; Schedler, M.; Glorius, F. An overview of N-hetercyclic carbenes. Nature, 2014, 510, 485.;
(c) Flanigan, D.M.; Romanov-Michailidis, F.; White, N.A.; Rovis, T. Organocatalytic reactions enabled by N-heterocyclic carbenes. Chem. Rev., 2015, 115, 9307.;
(d) Wang, M.H.; Scheidt, K.A. Cooperative catalysis and activation with N-heterocyclic carbenes. Angew. Chem., Int. Ed., 2016, 55, 14912.
(b) Richter, M.N.; Schedler, M.; Glorius, F. An overview of N-hetercyclic carbenes. Nature, 2014, 510, 485.;
(c) Flanigan, D.M.; Romanov-Michailidis, F.; White, N.A.; Rovis, T. Organocatalytic reactions enabled by N-heterocyclic carbenes. Chem. Rev., 2015, 115, 9307.;
(d) Wang, M.H.; Scheidt, K.A. Cooperative catalysis and activation with N-heterocyclic carbenes. Angew. Chem., Int. Ed., 2016, 55, 14912.
[3]
(a) Wang, N.; Yan, X.; Hu, Z.T.; Feng, Y.; Zhu, L.; Chen, Z.H.; Wang, H.; Wang, Q.L.; Ouyang, Q.; Zheng, P.F. Intramolecular H-bonds in an organocatalyst enabled an asymmetric Michael/alkylation cascade reaction to construct spirooxindoles incorporating a densely substituted cyclopropane motif. Org. Lett., 2022, 24(46), 8553-8558.
[http://dx.doi.org/10.1021/acs.orglett.2c03578] [PMID: 36377976];
(b) Wang, D.; Sun, J.; Han, Y.; Sun, Q.; Yan, C.G. An access to highly functionalized dihydrobenzofuran spirooxidole scaffolds. Org. Lett., 2022, 24(42), 7790-7795.
[http://dx.doi.org/10.1021/acs.orglett.2c03123] [PMID: 36239308];
(c) Biswas, S.; Balha, M.; Das, S.; Pan, S. C. Organocatalytic asymmetric reaction between α-cyano enones and dioxindoles: Synthesis of dihydrofuran-spirooxidoles. Asian J. Org. Chem., 2022.
[http://dx.doi.org/10.1002/ajoc.202200359];
(d) Chen, I.T.; Guan, R.Y.; Han, J.L. Asymmetric sequential vinylogous Mannich/annulation/acylation process of 2-ethylidene 1,3-indandiones and isatin N-Boc ketimines: Access to chiral spiro-oxindole piperidine derivatives. Adv. Synth. Catal., 2022, 364(15), 2613-2619.
[http://dx.doi.org/10.1002/adsc.202200465];
(e) Wang, K-K.; Li, Y-L.; Chen, R. Substrate-controlled regioselectivity switchable [3+2] annulations to access spirooxindoles skeletons. J. Org. Chem., 2022, 87, 8158.
[http://dx.doi.org/10.1021/acs.joc.2c00892] [PMID: 35675122];
(f) Warghude, P.K.; Bhowmick, A.; Bhat, R.G. Direct access to spirooxindole dihydropyrrole fused pyrazolones and bisspiropyrazolone derivatives. Tetrahedron Lett., 2022, 97, 153791.
[http://dx.doi.org/10.1016/j.tetlet.2022.153791];
(g) Shikari, A.; Mandal, K.; Chopra, D.; Pan, S.C. Organocatalytic asymmetric synthesis of cyclic acetals with spirooxindole skeleton. Adv. Synth. Catal., 2022, 364(1), 58-63.
[http://dx.doi.org/10.1002/adsc.202101057];
(h) Saito, S.; Katamura, T.; Tsukazaki, R.; Fujisawa, A.; Yoshigoe, Y.; Mutoh, Y. The aza-prins reaction of 1,2-dicarbonyl compounds with 3-vinyltetrahydroquinolines: Application to the synthesis of polycyclic spirooxindole dervatives. J. Org. Chem., 2021, 86(23), 16425-16433.
[http://dx.doi.org/10.1021/acs.joc.1c01785] [PMID: 34792347]
[http://dx.doi.org/10.1021/acs.orglett.2c03578] [PMID: 36377976];
(b) Wang, D.; Sun, J.; Han, Y.; Sun, Q.; Yan, C.G. An access to highly functionalized dihydrobenzofuran spirooxidole scaffolds. Org. Lett., 2022, 24(42), 7790-7795.
[http://dx.doi.org/10.1021/acs.orglett.2c03123] [PMID: 36239308];
(c) Biswas, S.; Balha, M.; Das, S.; Pan, S. C. Organocatalytic asymmetric reaction between α-cyano enones and dioxindoles: Synthesis of dihydrofuran-spirooxidoles. Asian J. Org. Chem., 2022.
[http://dx.doi.org/10.1002/ajoc.202200359];
(d) Chen, I.T.; Guan, R.Y.; Han, J.L. Asymmetric sequential vinylogous Mannich/annulation/acylation process of 2-ethylidene 1,3-indandiones and isatin N-Boc ketimines: Access to chiral spiro-oxindole piperidine derivatives. Adv. Synth. Catal., 2022, 364(15), 2613-2619.
[http://dx.doi.org/10.1002/adsc.202200465];
(e) Wang, K-K.; Li, Y-L.; Chen, R. Substrate-controlled regioselectivity switchable [3+2] annulations to access spirooxindoles skeletons. J. Org. Chem., 2022, 87, 8158.
[http://dx.doi.org/10.1021/acs.joc.2c00892] [PMID: 35675122];
(f) Warghude, P.K.; Bhowmick, A.; Bhat, R.G. Direct access to spirooxindole dihydropyrrole fused pyrazolones and bisspiropyrazolone derivatives. Tetrahedron Lett., 2022, 97, 153791.
[http://dx.doi.org/10.1016/j.tetlet.2022.153791];
(g) Shikari, A.; Mandal, K.; Chopra, D.; Pan, S.C. Organocatalytic asymmetric synthesis of cyclic acetals with spirooxindole skeleton. Adv. Synth. Catal., 2022, 364(1), 58-63.
[http://dx.doi.org/10.1002/adsc.202101057];
(h) Saito, S.; Katamura, T.; Tsukazaki, R.; Fujisawa, A.; Yoshigoe, Y.; Mutoh, Y. The aza-prins reaction of 1,2-dicarbonyl compounds with 3-vinyltetrahydroquinolines: Application to the synthesis of polycyclic spirooxindole dervatives. J. Org. Chem., 2021, 86(23), 16425-16433.
[http://dx.doi.org/10.1021/acs.joc.1c01785] [PMID: 34792347]
[4]
(a) Nair, V.; Vellalath, S.; Poonoth, M.; Mohan, R.; Suresh, E. N-heterocyclic carbene catalyzed reaction of enals and 1,2-dicarbonyl compounds: Stereoselective synthesis of spiro γ-butyrolactones. Org. Lett., 2006, 8(3), 507-509.
[http://dx.doi.org/10.1021/ol052926n] [PMID: 16435871];
(b) Dugal-Tessier, J.; O’Bryan, E.A.; Schroeder, T.B.H.; Cohen, D.T.; Scheidt, K.A. An N-heterocyclic carbene/Lewis acid strategy for the stereoselective synthesis of spirooxindole lactones. Angew. Chem. Int. Ed., 2012, 51(20), 4963-4967.
[http://dx.doi.org/10.1002/anie.201201643] [PMID: 22489096];
(c) Li, J.L.; Sahoo, B.; Daniliuc, C.G.; Glorius, F. Conjugate umpolung of β,β-disubstituted enals by dual catalysis with an N-heterocyclic carbene and a Brønsted acid: facile construction of contiguous quaternary stereocenters. Angew. Chem. Int. Ed., 2014, 53(39), 10515-10519.
[http://dx.doi.org/10.1002/anie.201405178] [PMID: 25124301];
(d) Zheng, C.; Yao, W.; Zhang, Y.; Ma, C. Chiral spirooxindolebutenolide synthesis through asymmetric N-heterocyclic carbenecatalyzed formal (3 + 2) annulation of 3-bromoenals and isatins. Org. Lett., 2014, 16(19), 5028-5031.
[http://dx.doi.org/10.1021/ol502365r] [PMID: 25230298];
(e) Mukherjee, S.; Joseph, S.; Bhunia, A.; Gonnade, R.G.; Yetra, S.R.; Biju, A.T. Enantioselective synthesis of spiro γ-butyrolactones by N-heterocyclic carbene (NHC)-catalyzed formal [3 + 2] annulation of enals with 3-hydroxy oxindoles. Org. Biomol. Chem., 2017, 15(9), 2013-2019.
[http://dx.doi.org/10.1039/C7OB00148G] [PMID: 28198907];
(f) Suresh, P.; Thamotharan, S.; Ganesan, S.S. Driving NHC organocatalysis on water through hydrophobic hydration for the synthesis of diverse heterocycles and carbocycles. Catal. Commun., 2018, 111, 47-51.
[http://dx.doi.org/10.1016/j.catcom.2018.03.024];
(g) Song, Z.Y.; Chen, K.Q.; Chen, X.Y.; Ye, S. Diastereo- and enantioselective synthesis of spirooxindoles with contiguous tetrasubstituted stereocenters via catalytic coupling of two tertiary radicals. J. Org. Chem., 2018, 83(5), 2966-2970.
[http://dx.doi.org/10.1021/acs.joc.7b03161] [PMID: 29405713];
(h) Ming, S.; Zhao, B.L.; Du, D.M. Chiral squaramide-catalysed enantioselective Michael/cyclization cascade reaction of 3-hydroxyoxindoles with α,β-unsaturated N-acylated succinimides. Org. Biomol. Chem., 2017, 15(29), 6205-6213.
[http://dx.doi.org/10.1039/C7OB01307H] [PMID: 28702662];
(i) Gao, Y.; Ma, Y.; Xu, C.; Li, L.; Yang, T.; Sima, G.; Fu, Z.; Huang, W. Potassium 2-oxo-3-enoates as effective and versatile surrogates for α,β-unsaturated aldehydes in NHC-catalyzed asymmetric reactions. Adv. Synth. Catal., 2018, 360(3), 479-484.
[http://dx.doi.org/10.1002/adsc.201701413];
(j) Xu, J.; Yuan, S.; Miao, M.; Chen, Z. 1-Hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed β-functionalization of saturated carboxylic esters: Access to spirooxindole lactones. J. Org. Chem., 2016, 81(22), 11454-11460.
[http://dx.doi.org/10.1021/acs.joc.6b02032] [PMID: 27709941];
(k) Zhu, S.Y.; Zhang, H.; Ma, Q.W.; Liu, D.; Hui, X.P. Oxidative NHC catalysis: Direct activation of β sp 3 carbons of saturated acid chlorides. Chem. Commun., 2019, 55(3), 298-301.
[http://dx.doi.org/10.1039/C8CC08578A] [PMID: 30506079]
[http://dx.doi.org/10.1021/ol052926n] [PMID: 16435871];
(b) Dugal-Tessier, J.; O’Bryan, E.A.; Schroeder, T.B.H.; Cohen, D.T.; Scheidt, K.A. An N-heterocyclic carbene/Lewis acid strategy for the stereoselective synthesis of spirooxindole lactones. Angew. Chem. Int. Ed., 2012, 51(20), 4963-4967.
[http://dx.doi.org/10.1002/anie.201201643] [PMID: 22489096];
(c) Li, J.L.; Sahoo, B.; Daniliuc, C.G.; Glorius, F. Conjugate umpolung of β,β-disubstituted enals by dual catalysis with an N-heterocyclic carbene and a Brønsted acid: facile construction of contiguous quaternary stereocenters. Angew. Chem. Int. Ed., 2014, 53(39), 10515-10519.
[http://dx.doi.org/10.1002/anie.201405178] [PMID: 25124301];
(d) Zheng, C.; Yao, W.; Zhang, Y.; Ma, C. Chiral spirooxindolebutenolide synthesis through asymmetric N-heterocyclic carbenecatalyzed formal (3 + 2) annulation of 3-bromoenals and isatins. Org. Lett., 2014, 16(19), 5028-5031.
[http://dx.doi.org/10.1021/ol502365r] [PMID: 25230298];
(e) Mukherjee, S.; Joseph, S.; Bhunia, A.; Gonnade, R.G.; Yetra, S.R.; Biju, A.T. Enantioselective synthesis of spiro γ-butyrolactones by N-heterocyclic carbene (NHC)-catalyzed formal [3 + 2] annulation of enals with 3-hydroxy oxindoles. Org. Biomol. Chem., 2017, 15(9), 2013-2019.
[http://dx.doi.org/10.1039/C7OB00148G] [PMID: 28198907];
(f) Suresh, P.; Thamotharan, S.; Ganesan, S.S. Driving NHC organocatalysis on water through hydrophobic hydration for the synthesis of diverse heterocycles and carbocycles. Catal. Commun., 2018, 111, 47-51.
[http://dx.doi.org/10.1016/j.catcom.2018.03.024];
(g) Song, Z.Y.; Chen, K.Q.; Chen, X.Y.; Ye, S. Diastereo- and enantioselective synthesis of spirooxindoles with contiguous tetrasubstituted stereocenters via catalytic coupling of two tertiary radicals. J. Org. Chem., 2018, 83(5), 2966-2970.
[http://dx.doi.org/10.1021/acs.joc.7b03161] [PMID: 29405713];
(h) Ming, S.; Zhao, B.L.; Du, D.M. Chiral squaramide-catalysed enantioselective Michael/cyclization cascade reaction of 3-hydroxyoxindoles with α,β-unsaturated N-acylated succinimides. Org. Biomol. Chem., 2017, 15(29), 6205-6213.
[http://dx.doi.org/10.1039/C7OB01307H] [PMID: 28702662];
(i) Gao, Y.; Ma, Y.; Xu, C.; Li, L.; Yang, T.; Sima, G.; Fu, Z.; Huang, W. Potassium 2-oxo-3-enoates as effective and versatile surrogates for α,β-unsaturated aldehydes in NHC-catalyzed asymmetric reactions. Adv. Synth. Catal., 2018, 360(3), 479-484.
[http://dx.doi.org/10.1002/adsc.201701413];
(j) Xu, J.; Yuan, S.; Miao, M.; Chen, Z. 1-Hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed β-functionalization of saturated carboxylic esters: Access to spirooxindole lactones. J. Org. Chem., 2016, 81(22), 11454-11460.
[http://dx.doi.org/10.1021/acs.joc.6b02032] [PMID: 27709941];
(k) Zhu, S.Y.; Zhang, H.; Ma, Q.W.; Liu, D.; Hui, X.P. Oxidative NHC catalysis: Direct activation of β sp 3 carbons of saturated acid chlorides. Chem. Commun., 2019, 55(3), 298-301.
[http://dx.doi.org/10.1039/C8CC08578A] [PMID: 30506079]
[5]
Trost, B.M.; Hirano, K. Dinuclear zinc catalyzed asymmetric spirannulation reaction: An umpolung strategy for formation of α-alkylated-α-hydroxyoxindoles. Org. Lett., 2012, 14(10), 2446-2449.
[http://dx.doi.org/10.1021/ol300577y] [PMID: 22545918]
[http://dx.doi.org/10.1021/ol300577y] [PMID: 22545918]
[6]
Wang, Q.L.; Peng, L.; Wang, F.Y.; Zhang, M.L.; Jia, L.N.; Tian, F.; Xu, X.Y.; Wang, L.X. An organocatalytic asymmetric sequential allylic alkylation–cyclization of Morita–Baylis–Hillman carbonates and 3-hydroxyoxindoles. Chem. Commun., 2013, 49(82), 9422-9424.
[http://dx.doi.org/10.1039/c3cc45139a] [PMID: 24005475]
[http://dx.doi.org/10.1039/c3cc45139a] [PMID: 24005475]
[7]
Chen, L.; Wu, Z.J.; Zhang, M.L.; Yue, D.F.; Zhang, X.M.; Xu, X.Y.; Yuan, W.C. Organocatalytic asymmetric Michael/cyclization cascade reactions of 3-hydroxyoxindoles with α,β-unsaturated acyl phosphonates for the construction of spirocyclic oxindole-γ-lactones/lactams. J. Org. Chem., 2015, 80(24), 12668-12675.
[http://dx.doi.org/10.1021/acs.joc.5b02253] [PMID: 26550839]
[http://dx.doi.org/10.1021/acs.joc.5b02253] [PMID: 26550839]
[8]
(a) Bergonzini, G.; Melchiorre, P. Dioxindole in asymmetric catalytic synthesis: routes to enantioenriched 3-substituted 3-hydroxyoxindoles and the preparation of maremycin A. Angew. Chem. Int. Ed., 2012, 51(4), 971-974.
[http://dx.doi.org/10.1002/anie.201107443] [PMID: 22173973];
(b) Bergonzini, G. Assessing the versatility of organocatalysis as a strategy for enabling novel asymmetric transformations, research thesis, 2010.
[http://dx.doi.org/10.1002/anie.201107443] [PMID: 22173973];
(b) Bergonzini, G. Assessing the versatility of organocatalysis as a strategy for enabling novel asymmetric transformations, research thesis, 2010.
[9]
(a) Zheng, Z; Perkins, B.L.; Ni, B. Diarylprolinol silyl ether salts
as new, efficient, water-soluble, and recyclable organocatalysts for
the asymmetric Michael addition on water. J. Am. Chem. Soc., 2010, 132, 50.;
(b) Ghosh, S.K.; Zheng, Z.; Ni, B. Highly active water-soluble and recyclable organocatalyst for the asymmetric 1,4-conjugate addition of nitroalkanes to α,β-unsaturated aldehydes. Adv. Synth. Catal., 2010, 352, 2378.;
(c) Ghosh, S.K.; Qiao, Y.; Ni, B.; Headley, A.D. Asymmetric Michael reactions catalyzed by a highly efficient and recyclable quaternary ammonium ionic liquid-supported organocatalyst in aqueous media. Org. Biomol. Chem., 2013, 11, 1801.;
(d) Ghosh, S.K.; Qiao, Y.; Chen, Q.; Ni, B.; Headley, A.D. Organocatalytic direct asymmetric crossed-Aldol reactions of acetaldehyde in aqueous media. J. Org. Chem., 2013, 78, 2693.;
(e) Kang, G.; Lin, S.; Shiwakoti, A.; Ni, B. Imidazolium ion tethered TsDPENs as efficient water-soluble ligands for rhodium catalyzed asymmetric transfer hydrogenation of aromatic ketones. Catal. Commun., 2014, 57, 111.
(b) Ghosh, S.K.; Zheng, Z.; Ni, B. Highly active water-soluble and recyclable organocatalyst for the asymmetric 1,4-conjugate addition of nitroalkanes to α,β-unsaturated aldehydes. Adv. Synth. Catal., 2010, 352, 2378.;
(c) Ghosh, S.K.; Qiao, Y.; Ni, B.; Headley, A.D. Asymmetric Michael reactions catalyzed by a highly efficient and recyclable quaternary ammonium ionic liquid-supported organocatalyst in aqueous media. Org. Biomol. Chem., 2013, 11, 1801.;
(d) Ghosh, S.K.; Qiao, Y.; Chen, Q.; Ni, B.; Headley, A.D. Organocatalytic direct asymmetric crossed-Aldol reactions of acetaldehyde in aqueous media. J. Org. Chem., 2013, 78, 2693.;
(e) Kang, G.; Lin, S.; Shiwakoti, A.; Ni, B. Imidazolium ion tethered TsDPENs as efficient water-soluble ligands for rhodium catalyzed asymmetric transfer hydrogenation of aromatic ketones. Catal. Commun., 2014, 57, 111.
