Nitroaldol reactions catalysis

Verkade and co-workers have shown the usefulness of their phosphazanes in various stoichiometric as well as catalytic reactions <1999PS(144)101>. Compound 290 was used to promote the cyanohydration of benzaldehyde with trimethylsilyl cyanide (TMSCN). The cyanohydrin was isolated in 95% yield, but no enantioselectivity was noticed <2002JOM(646)161>. Compounds 291 and 292 were attached to dendrimers and shown to be effective in the catalysis of Michael reactions, nitroaldol reactions, and aryl isocyanate trimerizations <2004ASC1093>. 

Stereoselective formation of carbon carbon and carbon heteroatom bonds remains an important goal in synthetic chemistry. Very recently lanthanide alkoxides were successfully utilized in enantioselective C-C bond forming reactions. Catalysis of aldol, cyanosilylation, nitroaldol and Michael reactions has been ascribed to the basic character of lanthanide alkoxides [158, 250, 251]. Ln3(OfBu)9 was successfully employed in test runs and subsequently optically active bidentate ligands were used (Fig. 35) [250a]. 

The LLB catalysts described above served an important role in demonstrating the proof of principle for catalysis with lanthanide-BINOL complexes. In addition, they were the first catalysts for the enantioselective nitroaldol reaction and gave respectable selectivities in synthetically useful yields. However, the reactions required at least 3.3 mol % of the catalysts for efficient conversion, and at that loading the reactions are rather slow. Clearly, the need for more effective catalysts is indicated. Consideration of the mechanism for the catalytic asymmetric... 

Scheme 1. Catalytic asymmetric nitroaldol reaction promoted by heterobimetallic lanthanoid catalysis LnLB...

In 1992, Shibasaki et al. reported for the time an application of chiral heterobimetallic lanthanoid complexes (LnLB) as chiral catalysts in asymmetric catalysis, namely the catalytic asymmetric nitroaldol reaction (Henry reaction), which is one of the most classical C-C bond forming processes [11]. Additionally, this work represents the first enantioselective synthesis of (3-nitroalcohol compounds by the way of enantioselective addition of nitroalkanes to aldehydes in the presence of a chiral catalyst. The chiral BINOL based catalyst was prepared starting from anhydrous LaCl3 and an equimolar amount of the dialkali metal salt of BINOL in the presence of a small amount of water [9]. 

A concept of multifunctional chiral catalysis, where the catalysts exhibit both Lewis acidity and Bronsted basicity was developed. The mnltifimctional catalysts were first reported in a catalytic asymmetric nitroaldol reaction using rare earfli metal complexes. Interestingly, heterobimetalhc... 

Although heterobimetallic complexes afforded nitroaldol adducts in good stereoselectivity, most reactions required a long reaction time even with relatively high catalyst loadings (3-10 mol%). To achieve a more efficient catalysis, a strategy to accelerate the reaction was investigated. A plausible mechanism of catalytic asymmetric nitroaldol reaction is shown in Scheme 13.42. The concentration of intermediate (A) was considered to be rather low in the reaction mixture because of an... 

The use of lanthanide complexes in asymmetric catalysis was pioneered by Danishefsky s group with the hetero-Diels-Alder reaction,and their utility as chiral Lewis acid catalysts was shown by Kobayashi. The Brpnsted base character of lanthanide-alkoxides has been used by Shibasaki for aldol reactions, cyanosilylation of aldehydes and nitroaldol reactions.The combination of Lewis acid and Brpnsted base properties of lanthanide complexes has been exploited in particular by Shibasaki for bifunctional asymmetric catalysis. These bimetallic lanthanide-main-group BINOL complexes are synthesized according to the following routes ... 

Heterobimetallic Catalysis with Amide-Based Ligand 3.1 Anti-Selective Catalytic Asymmetric Nitroaldol Reaction... 

Shibasaki M, Groger H (1999) Nitroaldol reaction. In Jacobsen EN, Pfaltz A, Yamamoto H (eds) Comprehensive asymmetric catalysis. Springer, Berlin, pp 1075-1090... 

Interfacially active guanidinium-thiourea bifunctional catalyst 190 catalyzes highly enantioselective nitroaldol reactions in the presence of an external base such as KOH in toluene/water biphasic conditions. Although the retro-nitroaldol reactions generally proceed under basic conditions, addition of KI inhibits the retro-process. A cooperative reaction mode between guanidinium and thiourea moieties is supported by experiments using structural variants of 190. A positive nonlinear effect is observed between the enantiomeric excess of 190 and the product 191. These results support the hypothesis that self-a egation of 190 is necessary for catalysis (Scheme 28.22) (96, 97). Catalyst 190 has been used in the synthesis of chiral tertiary alcohol products obtained in nitroaldol reactions of nitroalkanes and a-ketoesters [98],... 

Gruber-Khadjawi, M., Purkarthofer, T. Skranc, W. et al. (2007) Hydroxynitrile lyase-catalyzed enzymatic nitroaldol (Henry) reaction. Advanced Synthesis and Catalysis, 349, 1445-1450. 

The nitroaldol (Henry) reaction, first described in 1859, is a carbon-carbon bondforming reaction between an aldehyde or ketone and a nitroalkane, leading to a nitroalcohol adduct [29]. The nitroalcohol compounds, synthetically versatile functionalized structural motifs, can be transformed to many important functional groups, such as 1,2-amino alcohols and a-hydroxy carboxylic acids, common in chemical and biological structures [18, 20, 30, 31]. Because of their important structural transformations, new synthetic routes using transition metal catalysis and enzyme-catalyzed reactions have been developed to prepare enantiomerically pure nitroaldol adducts [32-34]. 

Vongvilai P, Larsson R, Ramstrom O (2008) Direct asymmetric dynamic kinetic resolution by combined lipase catalysis and nitroaldol (Henry) reaction. Adv Synth Catal 350 448 152... 

Recently, a new one-pot process for the sequence (i)-(iii) has been realized under heterogeneous catalysis (Ballini et al 2007b). In fact, treating at room temperature according to the reaction in Figure 2.20 one equivalent of primary haloalkanes (57) and one equivalent of aldehyde, or conjugate enone, in the presence of IR A-402 nitrite and Amberlyst A-21, the nitroalkanols (60) or y-nitro ketones (61) were obtained, respectively, in a one-pot SN2-nitroaldol (Henry) or SN2-Michael reactions. 

Khan, F. A., Dash, J., Satapathy, R., Upadhyay, S. K. Hydrotalcite catalysis in ionic liquid medium a recyclable reaction system for heterogeneous Knoevenagei and nitroaldol condensation. Tetrahedron Lett. 2004,45, 3055-3058. 

The Henry reaction or the nitroaldol is a classical reaction where the a-anion of an alkyinitro compound reacts with an aldehyde or ketone to form a p-nitroalcohol adduct. Over the decades, the Henry reaction has been used to synthesize natural products and pharmaceutical intermediates. In addition, asyimnetric catalysis has allowed this venerable reaction to contribute to a plethora of stereoselective aldol condensations. Reviews (a) Ballini, R. Bosica, G. Fiorini, D. Palmieri, A. Front. Nat. Prod. Chem. 2005, 1, 37-41. (b) Ono, N. In The Nitro Group in Organic Synthesis Wiley-VCH Weinheim, 2001 Chapter 3 The Nitro-Aldol (Henry) Reaction, pp. 30-69. (c) Luzzio, F. A. Tetrahedron 2001, 57, 915-945. 

Nitroaldol (Henry) Reactions with Bronsted Base Catalysis... 

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