Acyloxylation

Nonhindered phenols are acyloxylated by diacyl peroxides ia nonradical reactions (187) ... 

Free-radical acyloxylation of aromatic substrates has been accomplished with a number of reagents including copper(II) acetate,benzoyl peroxide-iodine, silver(II) complexes, and cobalt(III) trifluoroacetate. ... 

Vicinal iodo carboxylates may also be prepared from the reaction of olefins either with iodine and potassium iodate in acetic acid/ or with N-iodosuccinimide and a carboxylic acid in chloroform. " A number of new procedures for effecting the hydroxylation or acyloxylation of olefins in a manner similar to the Prevost or Woodward-Prevost reactions include the following iodo acetoxylation with iodine and potassium chlorate in acetic acid followed by acetolysis with potassium acetate reaction with iV-bromoacetamide and silver acetate in acetic acid reaction with thallium(III) acetate in acetic acid and reaction with iodine tris(trifluoroacetate) in pentane. ... 

Three different mechanisms of perester homolytic decay are known [3,4] splitting of the weakest O—O bond with the formation of alkoxyl and acyloxyl radicals, concerted fragmentation with simultaneous splitting of O—O and C—C(O) bonds [3,4], and some ortho-substituted benzoyl peresters are decomposed by the mechanism of decomposition with anchimeric assistance [3,4]. The rate constants of perester decomposition and values of e = k l2kd are collected in the Handbook of Radical Initiators [4]. The yield of cage reaction products increases with increasing viscosity of the solvent. 

Scheme 3 outlines synthetic strategies for the introduction of a range of substituents on the amide, alkoxyl and acyloxyl side chains. Hydroxamic esters 23 are readily synthesised from potassium salts of hydroxamic acids 21 according to Cooley et al.7 8 9 or by condensation of the corresponding acid chloride 24 with an alkoxyamine. 

A-Acyloxy-A-butoxyamides 29, with variable amide and acyloxyl side chains... 

Thus the impact of hydroxamic ester substitution through nitrogen at the ester oxygen is to raise the acyloxyl carbonyls into the range for acid chlorides and acid anhydrides.128... 

Steric effects on both the amide and the acyloxyl side chain are similar. Tert-butyl and adamantyl groups on the amide side chain in 29v, 29x, 29c, and 29e (Table 2 entries 53 and 54, 63 and 65) result in lower stretch frequencies that, on average, are only 40 cm-1 higher than their precurser hydroxamic esters. Streck and coworkers have suggested that such changes in dialkyl ketones can be ascribed to destabilisation of resonance form II through steric hindrance to solvation which, in the case of tert-butyl counteracts the inductive stabilisation.127... 

When comparing the series of (para-substituted benzoyloxy)benzyloxybenzamides (28a-j, Table 2, entries 43-52), one notable exception is the 4-methoxy analogue 28b, which exhibits a much lower carbonyl stretch at 1718 cm-1. The through resonance of the methoxyl lone pair reduces the electron-withdrawing effect of the acyloxyl substituent possibly resulting in a lower degree of pyramidality at the amide nitrogen and better resonance into the amide carbonyl. 

The situation with 7V-acyloxy-/V-alkoxyureas and carbamates is similar although infrared data were mostly determined by liquid film or condensed phase (KBr/nujol mull).52,131 However, the limited data for V-acyloxy-TV-alkoxyureas (Table 2, entries 69-72) give amide carbonyl frequencies ca. 1730 cm-1 that are raised by some 37-40 cm-1 by acyloxylation. Values for carbamates (Table 2, entries 73-77) are higher (mostly 1780 cm-1) but are raised to a lesser extent (10-20 cm-1) relative to their parent carbamates. Clearly, carbonyl vibrational frequencies will be influenced strongly by the adjacent amino or alkoxyl group in both analogues. 

The role of steric effects is unclear but the anomeric effect could also contribute to an increase in electron density at nitrogen. X-ray data for the two TV-acyloxy-TV-alkoxyamides, a urea and a carbamate outlined above show clear evidence, both from bond lengths and conformations, of an anomeric interaction RO-N bonds are short when compared to alkoxyamines. This interaction is responsible for SN1, SN2, homolytic and rearrangement reactions of /V-acyloxy-TV-alkoxyamides (vide infra) and has also been supported computationally. Acyloxylation of the hydroxamic esters results in both pyramidalisation as well as anomeric donation from the... 

Thus A-acyloxy-iV-alkoxyamides undergo acid-catalysed solvolysis forming A-acyloxy-A-alkoxynitrenium ions. However, the rate of uncatalysed reaction was negligible under the same conditions. Anomeric weakening of the N-O bond in the neutral species is insufficient to promote heterolysis. However, protonation of the acyloxyl group, renders this substituent at nitrogen more electronegative (Fig. 14a)... 

Electronic effects. Nucleophilic attack is favoured by electron-withdrawing groups on the amide and the acyloxyl side chains. Interpolated bimolecular rate constants at 308 K for the series of para-substituted /V-acetoxy-/V-butoxybenzamides 25c, 26b-g and 26i (Table 5) gave a weak but positive Hammett correlation with a constants ip = 0.13, r = 0.86).42,43 These Sn2 reactions are analogous to those of aniline and substituted pyridines with phenacyl bromides, which have similar Arrhenius activation energies and entropies of activation in methanol (EA= 14-16 kcal mol-1, AS = — 27 to —31 calK-1 mol-1) and 4-substituted phenacyl halides afforded a similar Hammett correlation with pyridine in methanol (cr, p — 0.25).175... 

Formation of both adduct 106, mesitylene adduct 109 and heterocycle 104 can be ascribed to homolysis (Scheme 21, pathway (i)). Decarboxylation of acyloxyl radical gives radicals, R , which either combine with the persistent free radical 102 giving 106 or, by abstracting hydrogen from solvent, give 3,5-dimethylbenzyl radicals, which combine with 102 to give 109. 

FIERON reactions of 7V-acyloxy-7V-alkoxyamides would be expected to favour migration of acyloxyl groups since anomeric effects are strongest in this direction... 

The magnitude of the activation energies indicates that such migrations are unlikely to compete with heterolysis of the N-OAc in polar solvents. While the influence of the spectator sodium ion on these reactions is unknown, clearly the ESI-MS-MS data reflects the expected migration tendencies of acyloxyl versus... 

The formation of anhydrides 101 in the thermal decomposition reactions of TV-acyloxy-TV-alkoxyamides in non-polar mesitylene (Scheme 21, pathway (ii)) can thus be attributed to HERON migration of acyloxyl groups. However, the similarity of Eas for the two isomeric transition states raises the possibility that in these reactions some, or all of the ester might be generated by HERON migration of the alkoxyl substituent (Scheme 21, pathway (iii)). 

Log P is the hydrophobicity (log octanol-water partition coefficient) calculated according to the Ghose-Crippen algorithm.201 dpifA of the carboxylic acid corresponding to the W-acyloxyl substituent. 

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