Reversible nitroaldol reaction

Detailed time-dependent NMR studies were also performed in order to evaluate the kinetic profile of the tandem reaction (Fig. 6.17). Experimental data was coherent with a reversibly-irreversihly-coupled model, suggesting the proposed rearrangement step to he faster compared to the iminolactone cycfizafion. The studies also revealed the forward nitroaldol formation to he of comparable rate to tandem cycfizafion, while the reverse nitroaldol reaction was slower and thereby rate determining for the overall DCR process. 

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... 

Due to the reversibility of this nitroaldol reaction, the easy epimerization at the nitro-sub-stituted carbon, and the often low yields in reactions with nitro compounds other than ni-tromethane, few stereoselective additions have been reported. Highly stereoselective reactions are known for the synthesis of cyclic systems (see Section 1.3.5.6.6.). 

Intermolecular reaction of the mannose-derived 2,3-0-isopropylideiie-a-D-/y.vc>-pentodialdo-l,4-furanoside 13 affords a diastereomeric mixture of nitroalcohols 14. Upon fluoride-catalyzed desilylation, a stereoisomerically pure nitrocyclitol 15 was obtained from a successive intramolecular nitroaldol reaction as a consequence of the reversibility of the nitroaldol reaction which, in this case, allows the equilibration of isomers through open-chain intermediates33. 

The LLB type catalysts were also successfully applied in the asymmetric ni-troaldol reaction of quite unreactive a,a-difluoro aldehydes. However, catalytic asymmetric nitroaldol reaction of a broad variety of a,a-difluoro aldehydes proceeded satisfactorily when using the heterobimetallic asymmetric catalysts with modified, 6,6 -disubstituted BINOL ligands [22]. The best results were obtained with the samarium (III) complex (5 mol%) generated from 6,6 -bis[(tri-ethylsilyl)ethynyl BINOL with enantioselectivities up to 95% ee. The ( -configuration of one representative nitroaldol adduct showed that the nitronate reacted preferentially on the Si face of aldehyde in the presence of (P)-LLB (20 mol% 74% yield 55% ee). It is noteworthy that the enantiotopic face selection for a,a-difluoro aldehydes is reverse to that for nonfluorinated aldehydes. The stereoselectivity for a,a -difluoro aldehydes is identical with that of P-oxa-aldehydes, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

The butyrolactone skeleton of precursors for the sugar component of the glycoside antibiotics L-ristosamine and L-daunosamine can be readily assembled by a nitroaldol reaction of 3-nitropropionate (553) with 831, followed by lactonization [229] (Scheme 111). The initial condensation gives 832 in only moderate yield, probably due to the reversible nature of the nitroaldol reaction. If the crude product is treated with pyridinium tosylate, a mixture of lactones 833 and 834 is produced with concomitant loss of the THP group. The ratio of lactones is dependent on the base used in the nitroaldol condensation. Use of potassium tert-butoxide affords a 2 1 mixture of 833 and 834. The ratio can be increased to 5 1 with KF 2H20/tetrabutylammonium chloride, but the overall yield decreases. 

Fig. 7 (a) Selection-amplification of porphyrin tetrameric boxes using olefin metathesis, (b) Structure of dynamers formed via reversible Diels-Alder reaction, (c) Generation of a DCL of (R) and (S) nitroaldols from five differently substituted benzaldehydes... 

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

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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