Carbonium ions, acylation Carbonylation

Presence of a phenyl 6ubetitu nt at C(jj, as in 2,3-epoxy-3-phemy) -cyclohexanone caused a preponderance of acyl migration (Eq. 47. j. presumably by stabilizing the carbonium ion generated by Cjar bond rupture. Formation of a oerbonium ton at Ct ) rather than is favored also on electrostatic grounds by the proximity of C( to tlie positive terminal of the carbonyl dipole.8 ... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

Note that there are neither steric nor electronic factors that operate to favor equation (2). Consequently, the protonation of the carbonyl oxygen of benzoic acid is the favored process, and not an acyl carbonium ion process. 

Hydroxyamino)benzodiazepine (90) is acylated on oxygen upon reaction with acid chlorides (acetyl or benzoyl chloride) or isocyanates (methyl isocyanate) in the cold. On heating with acetic anhydride at 100°C, there is an oxido-reductive rearrangement to give the 3-acetoxy-2-methylamino derivative (91) (Scheme 14). This is considered to proceed by isomerization of the nitronium ion formed by cleavage of the N—O bond to the 3-carbonium ion which is trapped by the nucleophile (acetate) <80AP(313)926>. A similar mechanism is used to explain the formation of the 3-(l-imidazolyl) derivative (92) on reaction of (90) with carbonyl diimidazole. 

A convenient way to summarize the reactions of coenzyme A thioesters is by reviewing the )3-oxidation pathway for fatty adds". Fatty acid activation occurs by acylation of the coenzyme A thiol by way of an acyl adenylate. This is then dehydrogenated to an o,/3-enoyl acyl coenzyme A derivative by a flavin-dependent dehydrogenase. The ability of the adjacent carbonyl to provide resonance stabilization of the product appears to be an important aspect of this reaction. Such flavin-dependent dehydro- nations occur in other reaction sequences, but only where carbonyl resonance stabilization is possible. Water adds to the a,j8-enoyl thioester to generate a j8-hydroxy fatty acid derivative, a reaction facilitated by j8-carbonium ion stabilization in enoyl thioesters. The j3-hydroxyl is next... 

If carbonyl protonation fails to occur in aromatic amides where extra resonance stabilization of the carbonium ion is possible, one would scarcely think that it would be important for aliphatic amides. However, the data of Martin and Reese (248) show that increased branching of the acyl portion of the molecule (from acetamide to pivalamide) decreases the basicity to perchloric acid titration in acetic acid as would be expected for hyperconjugative stabilization of a carbonium-like species formed by oxygen protonation. Again, solvation may be the deciding factor. In contrast, the stabilities of iodine complexes of a few acyl substituted A, iV-dimethyl acetamides follow inductive rather than hyperconjugative order (97). 

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