Nitroalkenes aliphatic

Proline derivatives possess a prominent position among the aminocatalysts utilised for carbonyl activation. In combination with the readily tunable properties of the (thio)urea functionality for electrophile activation, the development of bifunctional chiral pyrrolidine-based (thio)ureas was a rational extension. In 2006, Tang and coworkers reported thiourea 55 that can catalyse the conjugate addition reaction between cyclohexanone and nitroalkenes (Scheme 19.63). In the presence of 20 mol% of chiral thiourea 55 and butyric acid as the cocatalyst, the q -products were delivered in high yields (up to 98%) and in excellent diastereo- (up to >99 1 dr) and enan-tioselectivities (up to 98% enantiomeric excess). In addition to aromatic nitroalkenes, aliphatic nitroalkenes were also tolerated, but required a long reaction time (6 days). 

Formic acid is a good reducing agent in the presence of Pd on carbon as a catalyst. Aromatic nitro compounds are reduced to aniline with formic acid[100]. Selective reduction of one nitro group in 2,4-dinitrotoluene (112) with triethylammonium formate is possible[101]. o-Nitroacetophenone (113) is first reduced to o-aminoacetophenone, then to o-ethylaniline when an excess of formate is used[102]. Ammonium and potassium formate are also used for the reduction of aliphatic and aromatic nitro compounds. Pd on carbon is a good catalyst[103,104]. NaBH4 is also used for the Pd-catalyzed reduction of nitro compounds 105]. However, the ,/)-unsaturated nitroalkene 114 is partially reduced to the oxime 115 with ammonium formate[106]... 

Seebach and Brenner have found that titanium enolates of acyl-oxazolidinones are added to aliphatic and aromatic nitroalkenes in high diastereoselectivity and in good yield. The effect of bases on diastereoselectivity is shown in Eq. 4.59. Hydrogenation of the nitro products yields y-lactams, which can be transformed into y-amino acids. The configuration of the products is assigned by comparison with literature data or X-ray crystal-structure analysis. 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Viologen salts act as one-electron phase-transfer agents and, in conjunction with sodium dithionite which regenerates the bipyridinium radical cation, they have been used for the debromination of 1,2-dibromoalkanes to yield alkenes in variable yields [13-15]. Nitroarenes are reduced to anilines in high yield (>90%) under similar conditions [16], whereas conjugated nitroalkenes are converted into the oximes of the saturated ketones [17] saturated aliphatic nitro compounds are not reduced by this process. 

A -Formylnorephedrine (149) has been employed as the first chiral hydroxide equivalent in conjugate additions to aliphatic (Ej-nitroalkenes (150 R = Me, Et, Pr, Pr , Bu, cyclohexyl, Ph, furyl, ferrocenyl, etc.) good yields (35-87%) and excellent diastereoselectivities (94-98% de) have been attained. Transition states, accounting for the overall stereochemical outcome, were presented. ... 

Akiyama and coworkers extended the scope of electrophiles applicable to asymmetric Brpnsted acid catalysis with chiral phosphoric acids to nitroalkenes (Scheme 57). The Friedel-Crafts alkylation of indoles 29 with aromatic and aliphatic nitroalkenes 142 in the presence of BINOL phosphate (7 )-3r (10 mol%, R = SiPhj) and 3-A molecular sieves provided Friedel-Crafts adducts 143 in high yields and enantioselectivities (57 to >99%, 88-94% ee) [81]. The use of molecular sieves turned out to be critical and significantly improved both the yields and enantioselectivities. 

Scheme 6.103 Representative products provided from the 100-catalyzed asymmetric Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes.

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

In the presence of thiourea catalyst 122, the authors converted various (hetero) aromatic and aliphatic trons-P-nitroalkenes with dimethyl malonate to the desired (S)-configured Michael adducts 1-8. The reaction occurred at low 122-loading (2-5 mol%) in toluene at -20 to 20 °C and furnished very good yields (88-95%) and ee values (75-99%) for the respective products (Scheme 6.120). The dependency of the catalytic efficiency and selectivity on both the presence of the (thio) urea functionality and the relative stereochemistry at the key stereogenic centers C8/C9 suggested bifunctional catalysis, that is, a quinuclidine-moiety-assisted generation of the deprotonated malonate nucleophile and its asymmetric addition to the (thio)urea-bound nitroalkene Michael acceptor [279]. 

Scheme 6.138 Product range of the 121-catalyzed asymmetric (3-hydroxylating Michael addition of oximes to aliphatic nitroalkenes. The product configurations were not determined.

Various approaches have been used to prepare pyrroles on insoluble supports (Figure 15.1). These include the condensation of a-halo ketones or nitroalkenes with enamines (Hantzsch pyrrole synthesis) and the decarboxylative condensation of N-acyl a-amino acids with alkynes (Table 15.3). The enamines required for the Hanztsch pyrrole synthesis are obtained by treating support-bound acetoacetamides with primary aliphatic amines. Unfortunately, 3-keto amides other than acetoacetamides are not readily accessible this imposes some limitations on the range of substituents that may be incorporated into the products. Pyrroles have also been prepared by the treatment of polystyrene-bound vinylsulfones with isonitriles such as Tosmic [28] and by the reaction of resin-bound sulfonic esters of a-hydroxy ketones with enamines [29]. 

Bicyclic nitroso acetals were able to be synthesised by employing ethyl vinyl ether (dienophile), styrene (dipolarophile) and the previously discussed resin-bound ni-troalkenes in a one-pot tandem [4+2]/[3+2]. As illustrated in Scheme 7.30, several aromatic and aliphatic substituents could be introduced to the bicyclic scaffold. Reductive cleavage of the cycloadducts with lithium aluminium hydride (LLAIH4) gave rise to the 3a-methyl alcohol substituted nitroso acetals in moderate overall yields. All these examples demonstrate that resin-bound nitroalkenes can be readily synthesised by microwave synthesis and thereafter can be used as starting materials, in a variety of high pressure-promoted cycloadditions. 

The relative Michael-acceptor abilities of a variety of substituted aromatic and aliphatic nitroalkenes have been elucidated by computational methods. Several global and local reactivity indices were evaluated with the incorporation of the natural charge obtained from natural bond orbital (NBO) analysis. Natural charges at the carbon atom to the NO2 group and the condensed Fukui functions derived by this method were found to be consistent with the reactivity.187... 

A highly enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported that employs a newly developed Ni(II)-(bis)diamine-based catalyst (174). The reaction scope includes substituted and unsubstituted malonates, /3-keto esters, and nitroalkenes bearing aromatic and aliphatic residues.202... 

The aim of this chapter is to show some representative examples in which aliphatic nitrocompounds are the key starting materials for the synthesis of different targets in a one-pot process. Thus, the availability of a variety of nitroalkenes and nitro-alkanes, their chemical versatility and their reactivity make these compounds highly powerful precursors and intermediates in environment-friendly organic synthesis. 

Aliphatic nonconjugated nitroalkenes can be reduced to the saturated nitro compounds without difficulty using platinum or palladium catalysts. A similarly situated alkynic group too is reduced selectively using Pd. 

In the course of the last two decades the chemistry of aliphatic nitro compounds- both nitroaJkanes and nitroalkenes has received particular attention. A variety of compounds have been obtained and their properties examined. 

The following are data in ethanol [4] which illustrate the effect of lengthening the conjugated system in aliphatic unsaturated compounds Table (13). Kochany and Piotrowska [10] examined the ultraviolet-spectra of a number of nitroalkenes. Their w — tt were observed between 360 and 420 run. The ultraviolet absorption spectra of nitroethylene, nitropropenes and nitro methane have been taken and interpreted with the Pariser-Parr-Pople self-consistent field — MO calculation. The absorption bands it it are in good agreement with calculated values [11]. 

It may also be seen from the above equations that at least 1 mol of water is required per mol of nitroalkene in order to secure reduction to the oxime. We prefer, however, to utilize a considerable excess of water in order to obtain a mixture which can be satisfactorily handled, and agitated during the reaction. Other solvents can be employed in conjunction with water if desired, but these should preferably be miscible with water in order to maintain a single liquid phase and thus facilitate the reduction. The use of an organic solvent in conjunction with water may be an advantage in controlling the type of reduction product secured. Thus, if it is desired to obtain the oxime rather than the ketone, the use of an aliphatic alcohol in conjunction with water will tend to increase the ratio of oxime to ketone in the products. 

The nitroalkene intermediate can either form the dinitro product or go through a Michael-type addition with the encapsulated PEI. Eurthermore, because capsules swollen in methanol retain their catalytic activity when placed in toluene, the reaction can be run in a mixture of two different solvents. This allows both the encapsulated PEI and the nickel catalyst to operate in their respective ideal solvents, namely methanol and toluene. To demonstrate the scope of this one-pot process, the reaction was performed with dimethyl malonate (138) and various aromatic and aliphatic aldehydes. Table 3.13 shows the results. 

Evidently, although the system tolerates both aromatic and aliphatic aldehydes, the introduction of an electron-withdrawing substituent on the aromatic substrate results in a decreased yield. To gain information about the mechanism of the overall tandem reaction, kinetic studies were carried out to identify the rate-determining step. Changing the catalyst concentration in the reaction between 3-methylbutyraldehyde, nitromethane and dimethyl malonate revealed that the reaction is first order in nickel catalyst, indicating that the Michael addition of dimethyl malonate to the nitroalkene is the ratedetermining step. 

The cerium(III)-mediated conjugate addition of a difluoromethylphosphonate carbanion to a wide range of aliphatic nitroalkenes,acyclic and cyclic vinyl sulfones,5 and vinyl sulfoxides has been reported recently (Scheme 3.85). 

The double deprotonation of 2-arylnitroethanes followed by treatment wiA electrophiles led to 2-sub-stituted-2-arylnitroethanes. This fact suggested that the strong base sequentially abstracted a- and then (3-protons of these substrates giving a,(3-dianions (57). The same behavior has been observed with primary nitroalkanes having a vinyl or carbonyl group on the 3-carbon. If there is only one a-nitro CH as in open-chain and cyclic secondary nitroalkanes, bis(lithioxy)enamines (58) and (59) (dianion derivatives of a-nitroalkenes, also called super enamines) are generate and exclusively those with a terminal double bond in the case of 2-nitroalkanes (equations 22 and 23). These dianion derivatives react with aromatic and aliphatic aldehydes as well as ketones to give 1,3-difunctional derivatives. In contrast to the lack of... 

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