Phenylation chemoselective

Chemoselective alkenylation in the C-3 position of N-substituted 3,5-dichloropyrazin-2(lH)-ones has been described by Van der Eycken et al. [27]. When a mixture of N-substituted 3,5-dichloropyrazin-2(lH)-one, ethyl acrylate, and NEts in DME, using Pd(OAc)2/DTPB [2-(di-f-butylphosphanyl)bi-phenyl] as a precatalyst, was irradiated for 15 min at 150 °C, the desired /1-fimctionabzed ethyl acrylates could be obtained in moderate yields (Scheme 81). When styrene was used as an alkene, a mixture of E and Z products was isolated. The type of catalyst used proved to be important to avoid competitive Diels-Alder reaction of ethyl acrylate with the hetero-diene system of 3,5-dichloro-l-benzylpyrazin-2(lH)-one. 

Chemoselective anodic methoxylation at a distinct carbon atom in the a-position to an amino group in a polypeptide was achieved by prior introduction of a silyl group as an electroauxiliary at this carbon atom [156]. Amide oxidation in A-acetylpyrrolidines substituted with electron-rich phenyl rings led to either methoxylation a to the nitrogen atom or in the benzylic position. Mechanistic studies indicate that both the amide and the phenyl oxidation compete, but intramolecular electron transfer leads to... 

The different synthetic applications of acceptor-substituted carbene complexes will be discussed in the following sections. The reactions have been ordered according to their mechanism. Because electrophilic carbene complexes can undergo several different types of reaction, elaborate substrates might be transformed with little chemoselectivity. For instance, the phenylalanine-derived diazoamide shown in Figure 4.5 undergoes simultaneous intramolecular C-H insertion into both benzylic positions, intramolecular cyclopropanation of one phenyl group, and hydride abstraction when treated with rhodium(II) acetate. 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

The substituent Rj at the central carbon atom has to be either H or NHCN. Replacing it by either a methyl, phenyl or amino group leads to a sharp decrease in chemoselectivity. 

Further improvements in the stereocontrol were achieved by changing the substitution pattern of the succinic anhydride 2-phenyl succinic anhydride (roc)-36 gave the best control giving the monosubstituted succinic ester (f )-37 and (S)-38 in 95% ee and 85% ee respectively (Scheme 9). Simple chemoselective reduction gave the corresponding y-lactones (R)-39 and (S)-40 in similar enantiomeric purity. 

A method was proposed [196] for the production of 4-phosphazenyl-2,3-dihydropyrrol-2-ones and 5-phosphazenyl-2-pyridones from p-(N-acylphosphazenyl)enamines of dimethyl acetylenedicarboxylate. The authors of [197] examined the chemoselective cycloaddition of C-aryl-N-phenyl nitrones at the 1,2 double bond of allenylphosphonates, leading to a mixture of adducts possessing pyrrolidine and isoxazolidine structures. 

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