Nitroaldol exchange

Figure 1.3 Reversible reactions used in (g) nitroaldol exchange, (h) acetal exchange,...

Oxime exchange Aldol exchange Nitroaldol exchange... 

Shibasaki et al. have reported an asymmetric nitroaldol reaction catalyzed by chiral lanthanum alkoxide 18 to produce an optically active 2-hydroxy-1-nitroalkane with moderate-to-high enantiomeric excesses (Scheme 8B1.10) [27]. Apparently this novel catalyst acts as Lewis base. The proposed reaction mechanism is shown in Scheme 8B1.11, where the first step of the reaction is the ligand exchange between binaphthol and nitromethane. This reaction is probably the first successful example of the catalytic asymmetric reaction promoted by a Lew i s base metal catalyst. Future application of this methodology is quite promising. 

In the preparation of dynamic nitroaldol systems, different aldehydes and nitroalkanes were first evaluated for reversible nitroaldol reactions in the presence of base to avoid any side- or competitive reactions, and to investigate the rate of the reactions. 1H-NMR spectroscopy was used to follow the reactions by comparison of the ratios of aldehyde and the nitroalcohols. Among various bases, triethylamine was chosen as catalyst because its reactions provided the fastest exchange reaction and proved compatible with the enzymatic reactions. Then, five benzaldehydes 18A-E and 2-nitropropane 19 (Scheme 9) were chosen to study dynamic nitroaldol system (CDS-2) generation, because of their similar individual reactivity and product stabilities in the nitroaldol reaction. Ten nitroaldol adducts ( )-20A-E were generated under basic conditions under thermodynamic control, showing... 

In order to increase the exchange rate, ten equivalents of triethylamine were added, and the dynamic system was generated at 40 °C. Figure 5 shows 1H-NMR spectra of the dynamic nitroaldol system at different reaction times. In the absence of any catalyst, none of the nitroalcohol adducts was observed, but addition of triethylamine resulted in efficient equilibrium formation (Fig. 5a). The aldehyde protons of compounds 18A-E were easily followed (10.0-10.5 ppm), as well as the a-protons of 2-nitropropane 19 and adducts 20A-E (4.5-6.5 ppm). The selected dynamic nitroaldol reaction proved to be stable without producing any side reactions within several days. 

The proposed mechanism for the asymmetric nitroaldol reaction catalyzed by heterobimetallic lanthanoid complexes is shown in Scheme 2 [9]. In the initial step, the nitroalkane component is deprotonated and the resulting lithium nitr-onate coordinates to the lanthanoid complex under formation of the intermediate I [ 10]. Subsequent addition of the aldehyde by coordination of the C=0 double bond to the lanthanoid(III) ionic center leads to intermediate II, in which the carbonyl function should be attacked by the nitronate via a six-membered transition state (in an asymmetric environment). A proton exchange reaction step will then generate the desired optically active nitroalkanol adduct with regeneration of the free rare earth complex LnLB. 

Phosphonium ionic liquids exchanged with bicarbonate and methylcarbonate anions have been found to catalyse efficiently the Henry addition of nitroalkanes to different aldehydes and ketones under solventless conditions. These ionic liquids not only allow the selective formation of nitroaldols but also unlock a novel high-yielding access to dinitromethyl derivatives of ketones. The reaction mechanism plausibly involves the transformation of the initial catalytic species [MeP(Octyl)3+ ROCOO R= Me, H] through reversible loss and uptake of carbon dioxide. 

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