Nitroalkanes building blocks

The cycloaddition, reduction and oxidation reactions emanating from a,/J-unsatu-rated nitroalkenes provide easy access to a vast array of functionalities that include nitroalkanes, N-substituted hydroxylamines, amines, ketones, oximes, and a-substi-tuted oximes and ketones [73-75], Consequently, there are numerous possibilities of using these in situ generated nitroalkenes for the preparation of valuable building blocks and synthetic precursors. 

Nitroalkane can be used as a convenient reagent for alkyl anion synthesis. Aliphatic nitro compounds can also be considered as versatile building blocks and intermediates in organic synthesis. They are readily available, and there are a wide variety of methods for converting the nitro group to other functional groups. 

The aza-Henry reaction of imines to nitroalkanes promoted by modified Cinchona alkaloids has been investigated by several groups. Optically active p-nitroamine products are versatile functional building blocks. In 2005 and 2006, several reports regarding use of chiral thioureas emerged, using nitroalkanes in the aza-Henry reaction to various imines. 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

The asymmetric catalytic nitroaldol reaction, also known as the asymmetric Henry reaction, is another example of an aldol-related synthesis of high general interest. In this reaction nitromethane (or a related nitroalkane) reacts in the presence of a chiral catalyst with an aldehyde, forming optically active / -nitro alcohols [122], The / -nitro alcohols are valuable intermediates in the synthesis of a broad variety of chiral building blocks, e.g. / -amino alcohols. A highly efficient asymmetric catalytic nitroaldol reaction has been developed by the Shibasaki group, who used multifunctional lanthanoid-based complexes as chiral catalysts [122-125],... 

Nitroalkanes provide products, which are especially versatile building blocks, since the nitro group introduced can be converted to several other functionalities. The examples shown in Eq. 58-61 include synthesis of regioisomeric 7-nitro-4-oxo-esters, of a cyclic system 141, and of a propenyl substituted derivative — all proceeding with good overall yield from easily available, inexpensive starting materials83 84 . 

NITROALKANES AS BUILDING BLOCKS FOR ONE-POT PROCESSES, VIA NITROALDOL (HENRY) REACTION... 

Three-component tandem cyHzations involving [2 -1- 4] and [2 -1- 3] additions can be performed vdth vinyl nitroalkanes bound to the polymer. In some cases, however, high pressure is necessary to perform the conversions [338, 339], Based on the design of the building blocks, reduction of the N-0 bonds formed in cycloaddition may lead to formal O-contraction, resulting in compact polycyclic amines of defined relative configurations [340]. 

The importance of nitroalkanes as building blocks and precursors of prim-amines and ketones is exemplified. 

Interconversion of the Nitro Group, Nitroalkanes as Building Blocks... 

Enantioselective conjugate reductions of /3, -disubstituted nitroalkenes have been developed by Carreira (Equation 50) [177, 178]. The reactions provide access to a range of versatile chiral building blocks as a consequence of the rich chemistry available to the nitroalkane products [179]. The optimal procedure prescribes the use of the commercially available Josiphos ligand 180 in combination with a Cu source. Although most halides (Cl, Br, I) were shown to inhibit the reductions [177], CUF2 was identified as a bench-stable and commercially available copper source for the reduction [178]. 

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