Neighboring group participation by the pyrrole nucleus

Using proton and carbon-13 NMR spectroscopy, the transformation of 2-hydroxyethylpyrroles (5,15) into 2-haloethylpyrroles by treatment with thionyl chloride or carbon tetrabromide/triphenylphosphine is shown to proceed by randomization of the two side-chain carbon atoms. A spirocyclopropylpyrrolium ion (19) is postulated as an intermediate in this unexpected process.     

Neighboring group participation of 9-anthracenylmethyl group in glycosylation: preparation of unusual C-glycosides

[reaction: see text] A coupling of 2-O-arylmethylated D-glucose-derived thioglycosides with various alcohols in the presence of DMTST as an activator is described. The requisite glycosyl donors are efficiently prepared by one-pot procedures. When the aryl groups are phenyl, p-methoxyphenyl, 1-naphthyl, and 2-naphthyl groups, a mixture of alpha- and beta-anomeric O-glycosides is obtained under the conditions, whereas when the aryl group is the 9-anthracenyl group, a highly stereoselective formation of the unusual C-glycosides in good yields via neighboring group participation of the 9-anthracenylmethyl group followed by coupling with a variety of alcohols is observed. Three new chiral centers including a quaternary carbon are created in one single step.     

Neighboring group participation and rearrangement in hypobromous acid addition to 10β-vinyl-cholestanes

Hypobromous acid addition to the diol $\text{Ia}$ yields two epimeric dibromo 6β,19a-epoxides $\text{III}$ and $\text{IV}$ in a 83:17 ratio. Under the same conditions the 6β-acetoxy derivative $\text{Ib}$ gives three products: $\text{III}$ (46%), its epimer $\text{VII}$ (5%) and the spyrocyclic ketone $\text{V}$ (49%).     

Neighboring group participation by sulfonamido nitrogen

The ability of sulfonamido nitrogen to enter into neighboring group participation was established in two different reaction settings. The first was uncovered during the bromination of benzodiazocine 8 in dichloromethane at 0 degrees C, and the second during the base treatment of 15a en route to allene 18.     

Fragmentation of protonated amides through intermediate ion-neutral complexes: Neighboring group participation

It has been shown that neighboring group participation plays an important role in the fragmentation of protonated amides; the attachment of an adjacent functional group capable of accepting a proton provides alternative pathways of low energy for the formation of the inevitable N-protonated species in the fragmentation of the amide bond. Under methane chemical ionization (CI) conditions, protonated aniline (m/z 94) is only 1. 6% of the base peak MH⁺ ion for acetanilide; the abundance of the m/z 94 ion is increased to 15% for acetoacetanilide and protonated o-methoxyaniline reaches a relative intensity of 49% for N-acetyl-o-methoxyaniline. A more striking difference in ease of the formation of protonated anilines is found for acetanilides bearing a nitro group at different positions. Protonated nitroaniline (m/z 139) is the base peak in the methane CI spectrum of N-acetyl-o-nitroaniline; the m/z 139 ion drops to only 0.7% for the para isomer, and this ion is increased to 31.5% in the spectrum of N-acetoaceto-p-nitroaniline. By employing low energy collision-induced dissociation, it has been found that the fragmentation of protonated amides proceeds by way of ion-neutral complexes. In the case of acetanilide, for example, the cleavage of the amide bond gives rise to an acetylium ion and neutral aniline, which are bound together as a complex. An α-hydrogen of the acetylium ion, which is activated by the positive charge, is captured by aniline due to its higher proton affinity as compared with ketene. For those compounds having mobile protons other than the amidic hydrogen, it is indicated that such proton has the priority to be transferred in the reaction. Thus, the proton on the free carboxyl group of N-phenyl succinic and maleic monoamides is transferred in the fragmentation, leading to anhydrides as the neutral species in the formation of protonated aniline.     

Neighboring amide group participation in ester aminolysis in aprotic solvents

The piperidinolysis of 8-quinolyl-, p-nitrophenyl-, o-, and p-piperidinocarbonylphenyl acetates in acetonitrile and in chlorobenzene was studied at 25°C. The strictly second order kinetic behaviour and the weaks solvent-dependence of the rate of the reaction of o-piperidinocarbonylphenyl acetate indicate anchimeric assistance by the o-amide group, and support the suggestion that amide groups of hydrophobic enzyme active sites may act as general base catalysts.

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8--, --, - - 25°C. - - , .

     

An unusual radical Smiles rearrangement

Radicals derived from N-(alpha-xanthyl)acetanilides or N-(alpha-xanthyl)acetylaminopyridines possessing a substituent next to the nitrogen undergo a hitherto undocumented Smiles rearrangement proceeding through a four-membered ring. It was also found that under certain conditions the amidyl radical produced by cleavage of the four-membered ring intermediate can undergo fragmentation to give an isocyanate. Such fragmentations are unprecedented at temperatures corresponding to refluxing benzene or chlorobenzene. [reaction: see text]     

Neighboring group participation in cyclodehydration. A regiospecific isoxazole synthesis

The regiospecific synthesis of isoxazoles 2, 11, 14 , and 15 is explained in terms of neighboring group participation of the ortho nitrogen of the heterocyclic ring in the cyclodehydration step.     

An unusual rearrangement of eudesmane skeleton

The lactone $\text{5}$ was found to be a co-product of the BF₃ etherate induced cyclization of epoxyisogermacrone $\text{2}$. The keton $\text{3}$ when treated with 100% HCOOH afforded the lactone $\text{5}$ while under the same conditions the ketol $\text{4}$ gave the corresponding ester $\text{6}$. A mechanism is suggested for the rearrangements.     

An unprecedented gedunin rearrangement reaction converts a methyl group into the methylene group of a cyclopropyl ring

Herein we describe an unprecedented formation of a cyclopropane ring through the conversion of a methyl group that was not functionalized for the purpose. In a one-step reaction, 7-deacetoxy-7α-hydroxygedunin (4) afforded two new gedunin derivatives, namely 7-deacetoxy-13,14,18-cyclopropyl-7α,15β, 17ξ-trihydroxy-gedu-16-oic acid (7) and 7-deacetoxy-9,11-en-7α,15β-dihydroxygedunin (8) along with the known 7-deacetoxy-7,9-diene-15β-hydroxygedunin (5).