Four hydroxyls are better than two. The use of a chiral lithium salt of 3,3 0 -bis-methanol-2,2 0 -binaphthol as a multifunctional catalyst of enantioselective Michael addition reactions Yuri N. Belokon a,⇑ , Zalina T. Gugkaeva a , Victor I. Maleev a , Margarita A. Moskalenko a , Alan T. Tsaloev a , Victor N. Khrustalev a , Karine V. Hakobyan b a Institute of Russian Academy of Sciences, A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov 28, 119991 Moscow, Russia b Yerevan State University, Department of Pharmaceutical Chemistry, A. Manoogian st. 1, 0025 Yerevan, Armenia article info Article history: Received 23 November 2010 Accepted 3 December 2010 Available online 12 January 2011 abstract The catalytic performance of the Li salt of (S)- or (R)-3,3 0 -bis[bis-(phenyl)hydroxymethyl]-2,2 0 -dihy- droxy-dinaphthalene-1,1 0 (BIMBOL) in asymmetric Michael additions of malonic acid derivatives and tol- uedine has been studied. Nitrostyrene and cyclohex-2-enone were chosen as Michael acceptors. Efficient asymmetric C–C and C–N bond formations with ee’s of up to 95% at room temperature were observed. A transition state model of the malonic ester addition to cyclohex-2-enone has been proposed based on the molecular structure of the acetone solvate of BIMBOL. The impact of the catalyst self-association on its performance is also discussed. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Asymmetric catalysts, which combine both acidic and basic sites, are attracting ever growing interest in the chemical commu- nity because of their greater effectiveness when compared to con- ventional catalysts that contain only either acidic or basic sites. Such multifunctional catalysts can exhibit both Lewis acidity and Brønsted basicity (heterobimetallic complexes), 1 and contain both Brønsted acidic and Brønsted basic sites (pure organic catalysts). 2 Another emerging simple multifunctional catalytic system is exem- plified by chiral lithium binaphtholate salts. 3c The catalysts contain a Lewis acidic site, and Brønsted basic, and Brønsted acidic sites within the confines of the same chiral molecules. The asymmetric reduction of ketones with trialkoxysilanes 3a and trimethylsilylcya- nation of aldehydes 3b have successfully been catalyzed by the mono lithium salt of (S)-BINOL as reported by Kagan et al. The approach was further extended by Nakajima to Mukaiyama-type aldol reac- tions of trimethoxysilyl enol ethers. 3c,3d An unexpected beneficial effect of water as an additive on stereoselectivity was observed in the reactions. 3d The catalytic effects of the lithium binolate were be- lieved to originate from the formation of chiral hypervalent silicon intermediates. 3a–d Ishihara broadened the use of lithium binolates to direct Mannich-type reaction of keto-esters and aldimines. 3e He also was the first to recognize the bifunctional (Lewis acidic and Brønsted basic) nature of the catalyst. 3e Previously, some of us developed a highly efficient approach for the asymmetric synthesis of aminoacids via phase transfer alkylation 4a,b and Michael reaction 4b,c of glycine Ni(II) complexes catalyzed by (S)- or (R)-2-amino-2 0 -hydroxy-1,1 0 -binaphthol (no- bin). 4a–c Alkalie metal nobinates were assumed to be the active cat- alytic species in the reactions, serving as a base to ionize the CH acid. 4b The conjugated acids of the nobinates were believed to be responsible for the asymmetric induction with the hydrogen bond solvating the glycine carbanion and simultaneously coordinating the alkalie metal cation in the transition state of alkylation. 4b We reasoned that further modification of the system by introducing additional hydrogen bond donor groups into the chiral binaphthole scaffold would further improve the performance of the chiral phe- nolate catalysts. In addition to greater stabilization of the charged intermediates, the longer hydrogen bond arrays would be expected to facilitate the mutual rigid fixation of the reagents in the transi- tion state of the bimolecular reactions of the electrophiles and the conjugated bases of the CH-acids. Finally, the classical condensa- tion reactions of the CH-acids, such as Michael, aldol, Mannich and so forth, are all formally C–C bond forming reactions, accom- panied by hydrogen (proton) migration from the CH acid to the electrophile. The creation of a chain of intramolecular hydrogen bonded hydroxyl groups could be expected to facilitate the proton transfer, accompanying the C–C bond formation, as Figure 1 illustrated. Some analogy can be found in the fast proton transport along one-dimensional water chains confined in carbon nanotubes. 5 0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2010.12.003 ⇑ Corresponding author. E-mail address: yubel@ineos.ac.ru (Y.N. Belokon). Tetrahedron: Asymmetry 22 (2011) 167–172 Contents lists available at ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy