Y-Nitro-ketones

Nitroparaffins add 1,4 to conjugated systems methyl vinyl ketones, for example, yield the corresponding y-nitro ketone, which can be reduced to a y-nitro alcohol (48). More than one vinyl group may react with primary nitroparaffins (49). 

The reduction of y-nitroketone acetals as in Eq. 6.50 with ammonium formate in the presence of Pd/C gives the corresponding amines in good yields. However, the reduction of y-nitro ketones are reduced to cyclic nitrones (Eq. 6.51).97 This reduction is far superior to the classical method using Zn/NH4C1 due to improved yield and simple workup. 

Similarly, pyrroline N-oxides (12), pyrrolines, or pyrrolidines can be prepared from y-nitro ketones (13) in aqueous organic media at low temperatures the pyrroline N-oxide is obtained66 [Eq. (26)]. 

Asymmetric Michael addition to to-nitrostyrenes,2 The enamine (2) formed from cyclohexanone and this prolinol derivative reacts with 2-aryl-1-nitroethylenes (3) to form, after acid hydrolysis of the primary adduct, essentially only one (4) of the four possible y-nitro ketones. 

Nef transformation,3 A versatile route to 1,4-diketones involves Michael addition of a nitroalkane to an a,/J-enone, which can be effected in 80% yield when catalyzed by fluoride ion (9, 446-447). The resulting y-nitro ketone is oxidized efficiently by a stoichiometric amount of KMn04 impregnated on silica gel to a 1,4-... 

In 1978, Wynberg and coworkers reported the first example of a chiral quaternary ammonium fluoride-catalyzed Michael addition of nitromethane to chalcone (Scheme 9.1) [3]. The reaction was performed in toluene at 20 °C with 10mol% of chiral ammonium salt 1 or 3a and excess potassium fluoride (KF, 15 equiv.), yielding the y-nitro ketone with 10-23% enantiomeric excess (ee). The requisite chiral... 

Highly enantioselective Michael addition of silyl nitronates (105) to cyclic o /3-unsaturated ketones (106 n = 0-2) has been accomplished by the utilization of N-spiro C2-symmetric chiral quaternary ammonium bifluoride (108) as an organocatalyst, offering a new route to the enol silyl ethers of scalemic y-nitro ketones (107 70-90% ee).156... 

The optically active y-nitro ketone products of type 8 were obtained with increased enantioselectivities of up to 76% ee. The yields remained in a medium to excellent range of up to 99%, and diastereomeric ratio of up to 98.5 1.5 were observed. So far, however, the long reaction time of 2-8 d represents a limitation which has to be further improved. A representative example is shown in Scheme 6. 

Kloetzel prepared various y-nitro ketones by a Michael-type condensation of nitroal-kanes with a,p-unsaturatcd ketones in the presence of diethylamine, and hydrogenated the y-nitro ketones thus obtained to the corresponding pyrrolidines in 51.5-94% yields over Raney Ni in methanol at 100°C and 6.9 MPa H2 in both the presence and absence of ammonia (eq. 9.30).55 It is noted that the hydrogenation of y-nitro phenyl ketones (R4 = Ph, eq. 9.30) over Raney Ni in the presence of ammonia yielded high yields of the corresponding pyrrolidines, which were obtained in only small quantities with use of platinum under the conditions of eq. 9.29. 

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. 

Deoxygenation of a nitrone. Some years ago Todd and co-workers noted that 1-pyrroline-1-oxides can be obtained by reductive cyclization of a y-nitro ketone. This reaction was used recently in a synthesis of chlonns related to vitamin B,. Thus the nitro ketone 1 on reduction with zinc and acetic acid gives the pyrroline N-oxide 2 in high yield. The N-oxide is stable to triphenylphosphiue or trimethyl phosphite, but is reduced to the imine 3 in high yield by TiCl,. 

Highly diastereo- and enantio-selective catalytic capture of chiral zinc enolates using nitroolefins as electrophiles has been described. The tandem y-nitro ketone products were obtained in the presence of a monodentate phosphoramidite ligand, in good yields with high diastereo- and enantio-selectivities (up to 96% ee). 

On a similar note, conjugate addition of Et2Zn to chalcones (266), catalysed by a complex of (TfO)2Cu and (269), generates zinc enolate (267), which can be captured by nitrostyrenes (259) to produce y-nitro ketones (268) with >20 1 dr and <95% ee " ... 

The y-nitro ketones 274 were also used as precursors in pyrrole synthesis. The reduction of the nitro compounds 274 by iron depending on the conditions and the substrate can give pyrroles 275a,b, dihydropyrroles 276b or pyrrolidinones 277c. It was also found that the di-hydropyrrole 276b can be transformed into pyrrole 275b in 25 % yield at reflux in nitrobenzene [94]. 

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