The Nitro-Aldol Henry Reaction

The nitro-aldol reaction between nitroalkanes and carbonyl compounds to yield [3-nitro alcohols was discovered in 1895 by Henry.1 Since then, this reaction has been used extensively in many important syntheses. In view of its significance, there are several reviews on the Henry reaction.2-5 These reviews cover synthesis of (3-nitro alcohols and their applications in organic synthesis. The most comprehensive review is Ref. 3, which summarizes the literature before 1970. More recent reviews are Refs. 4 and 5, which summarize literatures on the Henry reaction published until 1990. 

In general, the Henry reaction gives a mixture of diastereomers and enantiomers. The lack of selectivity is due to the reversibility of the reaction and the easy epimerization at the nitro-substituted carbon atom. Existing reviews have hardly mentioned the stereochemistry of the Henry reaction. Recently, Shibasaki has found that the modification of the Henry reaction can control the stereochemistry to give (3-nitro alcohols with high diastereo- and enantio-selectivity.6 In Section 3.3, the progress of the stereoselective Henry reaction and its application to biologically active compounds are discussed. 

The 3-nitro alcohols are generally obtained in good yield by the reaction of aldehydes with nitroalkanes in the presence of a catalytic amount of base. When aryl aldehydes are used, the (3-nitro alcohols formed may undergo elimination of water to give aryl nitroalkenes. Such side reactions are not always disadvantageous, for nitroalkenes are sometimes the ultimate target for the Henry reaction. The choice of reaction conditions is important to stop the reaction at the stage of 3-nitro alcohols in aromatic cases. 

---

THE NITRO-ALDOL (HENRY) REACTION (/7)-LnLB complex... 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

Jacobsen, E. The nitro-aldol (Henry) reaction, in The Nitro Group in Organic Synthesis (ed. Ono, N.), 30-69 (Wiley, New York, 2001). 

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. 

---