Amides isomerism

Fig. 17. Amide isomerism due to mesomeric forms resulting in (E) and (Z) isomers...

FIGURE 3. (a) Fadfe amide isomerism in anomeric amides (b) stabilization of inversion transition state... 

Anomeric effects are evident from dynamic NMR studies on at least one substrate, N-benzyloxy-Af-chlorobenzamide (2c) ". In acetone-de the benzyl aromatic signal (S 7.85) de-coalesced into two signals (ratio 2 1) close to 200 K, corresponding to a free energy barrier of ca 10-11 kcalmoH Amide isomerization appeared to be faster than N—0 rotation since benzoyl resonances were largely unaffected. 

In tolnene-rfg, below 217 K, the benzyl aromatic signal resolved into two and the ben-zylic protons became diastereotopic. The exchange process, which was characterized by 217 = 246 s and AG = 10.2 kcalmoU, is a complex process involving both rotation aronnd the O—N bond and inversion at nitrogen, bnt since barriers to the former process are small the barrier best reflects that for rotation away from the anomeric conformation (Fignre 13). The amide isomerization barrier is even lower and both energies are in accordance with theoretical calcnlations (10.7 and 7.7 kcalmoG, respectively, for A—O rotation and amide isomerism in A-chloro-A-methoxyformamide) . 

These results indicate that barriers to all isomerization processes in A-acyloxy-A-alkoxyamides are likely to be less than about 8 kcalmol. Like that for its A-chloro analogue, the amide isomerization barrier in 100 is too low to be observed by H NMR. While there is dehnihve X-ray and theoretical evidence for anomeric effects in A-acyloxy-A-alkoxyamides, in the case of 100 the barrier to isomerization about the A-OBn bond must be lower than 10.3 kcalmol, the barrier in the corresponding A-chlorohydroxamic ester (Section in.B.2). The no-Oj Q anomeric interaction in A-chloroadducts is predicted to be stronger than the uo-Oj oAcyi interaction on perturbation arguments . 

Shtamburg and coworkers have reported that A,A -dialkoxy-A,A -dicarboalkoxyhydra-zines (219) have lower barriers to amide isomerization and weaker anomeric interactions . They measured a barrier to amide isomerization of only 9.8 kcalmoD. Furthermore, benzylic methylenes in A-benzyloxy systems were isochronous down to at least —90°C. These results are in line with observations for the A,A -diacyl-A,A -dialkoxyhydrazines since, in the carboalkoxy systems, the nitrogen lone pairs are lowered in energy by the additional electron demand, thereby reducing both amide conjugation and anomeric overlap. 

Allylic amide isomerization, 117 Allylic amine isomerization ab initio calculations, 110 catalytic cycle, 104 cobalt-catalyzed, 98 double-bond migration, 104 isotope-labeling experiments, 103 kinetics, 103 mechanism, 103 model system, 110 NMR study, 104 rhodium-catalyzed, 9, 98 Allylnickel halides, 170 Allylpalladium intermediates, 193 Allylsilane protodesilylation, 305 Aluminum, chiral catalysts, 216, 234, 310 Amide dimers, NMR spectra, 282, 284 Amines ... 

In the presence of a cationic Rh[((/ )-binap)(cod)] complex, geranyl or neryl amides isomerize slowly to give a mixture of the corresponding enamide and dienamide (Scheme 20) (2). The optical purity of the chiral enamide is high, but the chemical yield is low. Certain cyclic allylic amides give the enamide isomers in a high ee. With a DIOP-Rh catalyst, prochiral allylic alcohols are converted to optically active aldehydes with low ee (31). 

In these equations 9 is the N-C-C-H dihedral angle. A similar treatment (160) gives equation (34) which neglects the effects of cis-trans amide isomerism. 

Examples. Either or both microwave reactors have been useful for processes such as esterification, amidation, transesterification, rearrangement, acetalization, nucleophilic substitution, hydrolysis of esters and amides, isomerization, decarboxylation, oxidation, elimination, etherification, and formation of aminoreductones. Examples of such reactions have been tabulated (2,3). 

Cox, C., Lectka, T. (2000). Synthetic Catalysis of Amide Isomerization. Accounts of Chemical Research, 33(12), 849-858. 

This stereochemistry is the opposite of that found in the j3-cyanostibazoles (XI-43) obtained from a Knoevenagel condensation of arylacetonitriles with pyridinealdehydes (see Table XI-25). Unfortunately, these results do not provide syntheses for both the ds- (XI-41) and the tram- (XI-4S) carboxystilbazoles because, although the nitriles can be hydrolyzed to the tram amides (XI-44), these amides isomerize when hydrolyzed further to yield the cis acids. ... 

The nucleophilic catalysis of amide isomerization, whereby the formation of a tetrahedral intermediate disrupts amide resonance and facilitates rotation about the C—N bond (Scheme 10), has hitherto remained uncharacterized. Now, two types have been demonstrated, each of them 1,8-disubstituted naphthalene derivatives. In the first. 

It has been shown that microwave irradiation speeds up the benzil-benzilic acid rearrangement and increases the yield of product. Spiro ketones of the type (223) have been found to be susceptible to nucleophilic-induced retro-Claisen condensations. These have led to molecular rearrangements that destroy spiro connectivity see Scheme 55. The rearrangements of radical anions derived from aliphatic ketones have been studied using electrochemical techniques. A model system has been unveiled in which nucleophilic catalysis of amide isomerization is characterized for... 

Fig. 5 Conformational preferences for proUne, 4-(5)- and 4-(l )-fluoroproline. Preferred equilibrium for cis-trans amide isomerism in proUne derivatives and stabilization of the tmns isomer by a n to Jt interaction...

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