Acetoxy halides

These compounds are not isolated, but used directly in situ for conjugate addition reactions (15-24). Another method for the preparation of such reagents (but with Zn instead of Li) allows them to be made from a-acetoxy halides ... 

Diols such as 87 are converted in excellent yields [89] into acetoxy chlorides (88) by treatment with trimethyl orthoacetate and trimethylsilyl chloride [90] or into acetoxybromides (89) with trimethyl orthoacetate and acetyl bromide [91]. These reactions proceed through nucleophilic attack on an intermediate l,3-dioxolan-2-ylium cation [91] with inversion of configuration. In the presence of an aryl substituent as in 87, displacement occurs exclusively at the benzylic position. With aliphatic diols such as 90, the halide is introduced mainly at the less hindered position and acetoxybromides 91 and 92 are formed in a ratio of 7 1. Treatment of the acetoxy halides 88 or 89 under mildly alkaline conditions affords epox.de 93 in 84-87% yield while the mixture of 91 and 92 is converted to epoxide 94 in 94% yield. Because both... 

Conversion to a more facile, sulfur-derived, leaving group can be achieved by treatment with sodium thiosulfate or salts of thio and dithio acids (75,87). Under anhydrous conditions, boron tribromide converts the 3 -acetoxy group to a bromide whereas trimethyl silyl iodide gives good yields of the 3 -iodide (87,171,172). These 3 -halides are much more reactive, even when the carboxyl group is esterified, and can be displaced readily by cyano and by oxygen nucleophiles (127). 

Displacement of an allylic halide is complicated by side reactions involving migration of the double bond. A good example is the reaction of 7a-bromo-3 -acetoxy-A -steroids (201) which gives, besides the expected... 

Weiss ° treated 16-dehydro- (6), 17a-acetoxy- (8), 17a-hydroxy- (9) and 17a-bromopregnan-20-one (11) with a solution of lithium, barium, calcium or sodium in liquid ammonia and reacted the intermediate enolate anion (7) with the appropriate alkyl halide. 

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... 

Lead tetra-acetate has also been used to cleave acids. The carboxyl group is replaced by halide or acetoxy. 

Nucleophilic attack by iV-methylaniline is favoured by electron-withdrawing groups on the amide and acyloxyl side chains. A series of / ara-substituted Af-acetoxy-Af-butoxy-benzamides (138) (Table 6) gave a weak but positive Hammett correlation with a constants (p = 0.13, r = 0.86) °. The analogous reactions of pyridine with para-substituted phenacyl halides in methanol afforded a similar Hammett correlation a, p = 0.25) . The bimolecular rate constants for the limited series of Ai-benzoyloxy-A-benzyloxybenzamides (139) in Table 6 correlated strongly with Hammett a constants (p = 1.7, r = 0.97) °. Stabilization of developing carboxylate character supported the computed charge redistribution in the transition state ... 

In order to achieve 2-nitration, acetyl nitrate may be used as the reagent, but unlike pyrrole a semi-stable adduct, 5-acetoxy-2,5-dihydro-2-nitrofuran, is formed as an intermediate product (Scheme 6.22). This eliminates acetic acid when treated with pyridine. Furan also undergoes initial bromination or chlorination (X = Br or Cl) in ethanol at -40 °C, but then addition of two ethoxyl units occurs with the expulsion of halide ion (Scheme 6.23). 

Nucleophilic-displacement reactions constitute some of the earliest known methods for the preparation of deoxyhalogeno sugars. A variety of leaving groups have been used, including sulfonyloxy (usually jP-tolylsulfonyloxy or methylsulfonyloxy), halide, triphenyl-methoxy (trityloxy), acetoxy, phosphate, and nitrate. As Barnett has surveyed the reactions in Volume 22 of this Series,1 this subject will not be discussed comprehensively in the present Chapter instead, only some general comments will mainly be made that will also be relevant to later discussions. 

Acylation of RMnI (10, 290).1 Acylating agents such as acyl halides and anhydrides react with RMnI to form ketones in high yield. This reaction can be used to provide acetoxy ketones, keto esters, keto nitriles, and diketones in generally high yield. 

General considerations, 281 Intramolecular Alkylaluminum halides, 5 Dicarbonylcyclopentadienylcobalt, 96 Meldrum s acid, 172 Specific reactions 2-Acetoxy-l, 3-butadiene, 71... 

Trimethylsilyl groups also may be lost from vinylic or allylic positions in the arylation reaction.70 Halide ion facilitates die desilylation as well as the loss of alkoxy and acetoxy groups. Inclusion of soluble silver salts in reactions where trimethylsilyl groups are lost prevents this reaction.70 The reaction in the absence of silver ion is useful for preparing styrene derivatives. However, they also may be prepared directly from aryl halides and ethylene in fair to good yields.71... 

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