Aryl nitrone

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

The one step domino cycloaddition-rearrangement process of A-aryl nitrones 78 to BCP (79) afforded spirocyclopropane-annelated pyridones 81 and benzazocinones 82 in good overall isolated yields <00SL1034>. 

Using a variety of NMR 2-D techniques, such as H-H COSY, C-H COSY, DEPT, HMBC, and NOESY, an accurate assignment of the signals of 18 a-(5-substituted-2-hydroxyaryl)-7V-aryl nitrones has been made (159). 

Treatment of various o-propargyl-aryl nitrones (777a—p) with potassium hydroxide or sodium methoxide in methanol at room temperature provides l,2-dihydro[c]benzazepin-3-ones (778a—p) (Scheme 2.323) (850, 851). The high yields and the surprisingly mild reaction conditions are particularly remarkable in view of the complex mechanistic pathway involved in the overall transformation. 

Waterbury LD, Wilcox AL, Carney JM, Mavandadi F, Danielzadeh A. 3,4,5-Trisubstituted aryl nitrone compounds and pharmaceutical compositions containing the same, US Patent No. 0078297, April 24, 2003. 

Flitter WD, Garland WA, Van-Meerveld BG, Irwin I. Aryl nitrone therapeutics and methods for treating inflammatory bowel disease, US Patent No. 6545056, April 08, 2003. 

Most cyclic and aryl nitronates are sohds at room temperature (41). However, the stability of aryl substituted nitronates is dependent on the configuration of the nitronate (40). For example, only the trans isomer of the ethyl nitronate of 4-nitrophenylnitromethane crystallizes from an analytically pure mixture of cis and trans isomers. The mass recovery reflects the percentage of the trans isomer in the original mixture. As expected, increasing substitution on the nitronate typically... 

Ein analoger Reaktionsweg wird bei der Cyclisierung des N-Aryl-nitrons IV mit Bromcyan zu I-(Ethoxycarbonyl-imino-methyl)-2-hydroxy-benzimidazol(66% Schmp. 127-132°) beobachtet591 ... 

Imidazole synthesis. A new synthesis of 4,5-diarylimidazoles (2) involves reaction of catalytic amounts of aqueous elhanolic K.CN with N-methyl-C-aryl nitrones (1), prepared by condensation of aryl aldehydes with N-methyl-hydroxylamine. The reaction involves an intermediate cyanoimine (n). 

A simple, original, and efficient stereoselective synthesis of 4-hydroxyalkyl-l,2-oxazetidines 29 based on the addition of a-lithiated aryloxiranes 53 to aryl nitrones 54 and subsequent 4-exo-tct cyclization of the corresponding intermediates, which are /3,7-epoxyhydroxylamines 55, has also been described (Scheme 14) <2006OL3923>. 

Optically active lithiated styrene oxides (R)- and (A)-56 were also found to add to aryl nitrones 54b,c,i with an excellent diastereo- and enantioselectivity leading to the formation of stereodefined hydroxylamines 57b,c,i and further to 1,2-oxazetidines 29b,c,i upon treatment with NaOH/7-PrOH (Scheme 15). 

Title 3,4,5-Trisubstituted Aryl Nitrone Compounds and Pharmaceutical Compositions Containing the Same D.L. Waterbury et al., US Patent 6,998,419 (February 14, 2006)... 

Azinemonoxides are cleaved by two distinct photochemical pathways. One involves oxygen migration and the other involves a pericyclic ring closure. 4) Both processes are represented in the mass spectra of the compounds. Similar rearrangements occur in both the photochemistry and mass spectrometry of aryl nitrones, aryl N-oxides and aromatic azoxybenzenes. )... 

An addition to the earlier cycloadditions is the self condensation of an N-methyl-C-aryl nitrone (18) in the presence of potassiunt cyanide (Scheme 4.2.8) [22, 23[. The reactions are carried out in mild conditions (room temperature overnight in aqueous ethanol), but although the yields are good there arc no obvious advantages over other methods which are available for making 4,5-diarylimidazoles. Oie nitrones (18) are, however, readily available from Af-aryl- or iV-alkylhydroxylamines and aryl aldehydes [24], and so there may be occasions when the approach could be useful. 

CsMes)M (i )-l,2-bis(diphenylphosphino)propane (H20)] were found to catalyze the 1,3-dipolar cycloaddition of some acyclic and cyclic nitrones with methacrolein with complete diastereoselectivity and good enantioselec-tivity. Some intermediates involved in the process were isolated and characterized and a catalytic cycle involving [M]-aldehyde, [M]-nitrone, and [M]-adduct species was proposed <2005JA13386>. The reactions of A -phenyl C-aryl nitrones with the electron-poor a-bromoacrolein were effectively catalyzed by Zn(ll) complexes such as 534 and afforded isoxazolidine-4-carboxaldehydes, with high diastereo- and enantioselectivity, that were reduced to the corresponding alcohols (Scheme 123) <2004TL4061>. 

Because of their reactivity, aryl hydroxylamines can sometimes be trapped by further reaction with another material present in the hydrogenation system. Aryl nitrones such as 17 are produced by the in situ condensation of the aryl hydroxylamine with an aldehyde which is present in the reaction medium (Eqn. 19.16).35 These reactions take place in good yield over a Urushibara nickel catalyst (Chapter 12) in aqueous alcohol at room temperature and four... 

Ai-Aryl nitrones combine rapidly with phosgene to give imine hydrochlorides that are chlorinated in the ring (predominantly at the 2- position). Reaction occurs at room... 

Fig. 10.3 The proposed mechanism for the reaction between phosgene and iV-aryl nitrones.

Another C-C-C-X fragment is shikimic acid-derived 4,5-epoxy-3-hydroxycy-clohex-l-ene-l-carboxylic acid [270]. The latter can be bound onto an amino group which is bound to TentaGel via a Gysen Linker (367) [322]. Subsequent esterification with alkyl or aryl nitrone acids according to Tamura et al. [323] was concurrent with [2 -i- 3]-cycloadditions to the allylic double bond. As a result, tricyclic lactones (370) were obtained, which could readily be modified in many ways to yield a wide variety of polyfunctional structures (Scheme 77). 

Another interesting cascade involving nitrones is the copper catalyzed reaction with alkynes to produce p-lactams that was originally reported by Kinugasa (72CC466). Stoichiometric amounts of copper(I) phenylacetylide (61) react with various aryl nitrones 62 in pyridine to give p-lactams 63 in 50-60% yield (equation (2)). In each case, only the czs-lactams were isolated. 

---