Nitrostyrene, activation

It is not surprising then that the first reported surface mediated reaction made use of vicinal dihalides. In addition to poly-p-nitrostyrene immobilized metallo-porphyrins and viologens were found to be catalytically active. Recently,... 

Enantioselective synthesis of the antidepressant rolipram can be done by the asymmetric Michael addition of the enolate of IV-acetyloxazolidone to nitrostyrene. Chirally branched pyrrolidones like rolipram are highly active antidepressants with novel postsynaptic modes of action. The synthesis is shown in Scheme 4.13.78... 

The pyridazine ring of 111 is formed from [4+2] atom fragments in the cyclization of 3-amino-2-chloromethyl-quinazolin-4-one with activated acrylthioamides. The saturated pyridazine ring of 111 aromatized spontaneously to give 112 (Equation 12). Reaction with io-nitrostyrene yielded the 3-nitro analogue of 112 <2003MOL401>. 

Another classical case with respect to ort/zo-effects is found for 2-nitrostyrene78. The conceivable regio- and stereo-specifically labelled 2-nitrostyrenes have, in addition to the ring-labelled isotopomer, been studied by collision activation mass spectrometry79. Undoubtedly, the most striking result was the nearly equal contribution of both (in the neutral molecule diastereotopic) hydrogens of the fi-carbon. 

Aspergillus niger was the biocatalyst of choice for the biohydrolysis of para-nitrostyrene oxide (see above). A selective kinetic resolution using a crude enzyme extract of this biocatalyst followed by careful acidification of the cooled crude reaction mixture afforded the corresponding (i )-diol in high chemical yield (94%) and good ee (80%). This key intermediate could then be transformed via a four-step sequence (Scheme 11) into enantiopure (i )-nifenalol, a molecule with -blocker activity, which was obtained in 58% overall yield [88]. 

To reduce to the active formula, see the zinc reduction as given in the reduction section, CPB, 16, 217 (1968). This reduction is specifically matched to 3-bromo-4,5-methylenedioxy-B-nitrostyrene and other highly substituted ring type styrenes and propenes. Zinc reductions carried out properly are very gentle and do not destroy delicate ring substituents, while some reductions do. Zinc reductions can reduce any nitrostyrene or propenes, but some of these compounds must use the zinc reduction. Which compounds Compounds with lots of ring substituents, like 2,5-dimethoxymethylenedioxy, 3-methoxy-4-0-carbethoxy, etc. This is not to say that some of the other reductions are not capable of gentle reductions. 

Hydroxy-B-methoxy-B-nitrostyrene. A solution of freshly distilled 2-hydroxy-3-methoxybenzaldehyde (5g), 2.5 ml of nitromethane and 2 g of ammonium acetate in 20 ml of glacial acetic acid is refluxed for two hours. Cool and pour the dark brown mixture into water and allow the gummy product to crystallize. Recrystallize from benzene with the acid of Norit. Yield 2.3 grams of yellow needles melting at 115-122°. This is also to be reduced to an active compound as described in JACS, 72, 2781. 

The Takemoto group synthesized a series ofdiaminocyclohexane-based thiourea derivatives (e.g., 12, 40, 57, and 58) for catalysis of the Michael addition [149-152] ofmalonates to trons-j3-nitrostyrenes (Figure 6.18) [129, 207]. In the model, Michael addition of diethyl malonate to trons-]3-nitrostyrene at room temperature and in toluene as the solvent tertiary amine-functionalized thiourea 12 (10mol% loading) was identified to be the most efficient catalyst in terms of catalytic activity (86%... 

Dixon et al. screened cinchonine-derived thioureas 117-120 for their performance in the dimethyl malonate Michael addition to tra s-(5-nitrostyrene in dichlo-romethane at room temperature and at -20°C [274]. As shown in Figure 6.38, all candidates revealed comparable activity, but monodentate hydrogen-bond donor 118 exhibited very low asymmetric induction producing the desired Michael... 

Ricci and co-workers introduced a new class of amino- alcohol- based thiourea derivatives, which were easily accessible in a one-step coupling reaction in nearly quanitative yield from the commercially available chiral amino alcohols and 3,5-bis(trifluoromethyl)phenyl isothiocyanate or isocyanate, respectively (Figure 6.45) [307]. The screening of (thio)urea derivatives 137-140 in the enantioselective Friedel-Crafts reaction of indole with trans-P-nitrostyrene at 20 °C in toluene demonstrated (lR,2S)-cis-l-amino-2-indanol-derived thiourea 139 to be the most active catalyst regarding conversion (95% conv./60h) as well as stereoinduction (35% ee), while the canditates 137, 138, and the urea derivative 140 displayed a lower accelerating effect and poorer asymmetric induction (Figure 6.45). The uncatalyzed reference reaction performed under otherwise identical conditions showed 17% conversion in 65 h reaction time. 

Scheme 6.157 Mechanistic proposal for the biflinctional coordination and simultaneous activation of 2,4-pentandione and trans-P-nitrostyrene through thiourea catalyst 148 leading to chiral Michael adducts.

The Michael reactions [149-152] between cyclohexanone and trons-nitroalkenes were also explored by Xiao and co-workers utilizing bifunctional pyrrolidine-thiourea 213 and the pyrrolidine-thioureas 214-217 (Figure 6.61) [344]. The model Michael reaction between cyclohexanone and trons-nitrostyrene identified water as the best solvent and 217 to be the most efficient catalysts concerning the activity and asymmetric induction (90% yield 96% ee dr 98 2 in 12 h at 35 °C) in the presence of benzoic acid (10mol%) as additive. The optimized catalytic system allowed the formation of a broad spectrum of Michael adducts such as 1-6 resulting from... 

Results of Dulog, Kern et ah, and a few others (27, 31) are summarized in Table I. From the ra values, toward the unsubstituted styrene-peroxy radical, the most reactive styrene—p-methoxystyrene—is three times as reactive as the least reactive, m-nitrostyrene. Thus, the best electron donor shows the highest reactivity (lowest enthalpy of activation) toward the electron-accepting styrene-peroxy radical. The deviations from unity of the rarb products measure the effects of substitution on the selectivity of the peroxy radicals. These products depart more from unity with increasing differences in the electron-donating and accepting properties of the nuclear substituents. The same trends appear within the other styrene combinations. 

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