Asymmetric catalysis nitroaldol reactions

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]. 

The Henry reaction or the nitroaldol is a classical reaction where the a-anion of an alkylnitro compound reacts with an aldehyde or ketone to form a 3-nitroalcohol adduct. Over the decades, the Henry reaction has been used to synthesize natural products and pharmaceutical intermediates. In addition, asymmetric 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. 

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... 

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... 

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