Acyl halides addition-elimination reactions

Transformations through 1,2-addition to a formal PN double bond within the delocalized rc-electron system have been reported for the benzo-l,3,2-diazaphospholes 5 which are readily produced by thermally induced depolymerization of tetramers 6 [13] (Scheme 2). The monomers react further with mono- or difunctional acyl chlorides to give 2-chloro-l,3,2-diazaphospholenes with exocyclic amide functionalities at one nitrogen atom [34], Similar reactions of 6 with methyl triflate were found to proceed even at room temperature to give l-methyl-3-alkyl-benzo-l,3,2-diazaphospholenium triflates [35, 36], The reported butyl halide elimination from NHP precursor 13 to generate 1,3,2-diazaphosphole 14 upon heating to 250°C and the subsequent amine addition to furnish 15 (Scheme 5) illustrates another example of the reversibility of addition-elimination reactions [37],... 

Acyl halides undergo addition-elimination reactions in which nucleophiles displace the halide leaving group. These compounds are so reactive that catalysts are usually not necessary for their conversion. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

The reaction may be reasonably explained by the smooth oxidative addition of benzylic and acyl halides to nickel to afford benzylnickel halides and acylnickel halides. The metathesis of these complexes could give the acylbenzylnickel complex, which upon reductive elimination would yield the benzyl ketone. 

Probably the nickel carbonyl-catalyzed synthesis of acrylates from CO, acetylene, and hydroxylic solvent (78) involves an acetylene-hydride insertion reaction, followed by a CO insertion, and hydrolysis or acyl halide elimination. The actual catalyst in the acrylate synthesis is probably a hydride formed by the reversible addition of an acid to nickel carbonyl. 

An unusual synthesis of acyldienes from conjugated dienes, carbon monoxide, and alkyl or acyl halides using cobalt carbonylate anion as a catalyst should be mentioned here (57). The reaction apparently involves the addition of an acylcobalt carbonyl to a conjugated diene to produce a l-acylmethyl-7r-allylcobalt tricarbonyl, followed by elimination of cobalt hydrocarbonyl in the presence of base. The reaction can thus be made catalytic. Since the reaction was discussed in detail in the recent review by Heck (59), it will not be pursued further here. 

The hydrocarboxylation reactions discussed above have been proposed to involve direct addition of water to the metal center prior to elimination of the product, analogous to the oxidative addition of hydrogen to a metal center at the end of a hydroformylation catalytic cycle. Another class of hydrocarboxylation reactions is more analogous to the haUde-promoted Monsanto acetic acid process, where one has a reductive elimination of an acyl halide species that is rapidly hydrolyzed with free water to generate the carboxylic acid and HX. 

Unlike their benzenoid counterparts, halogen substituents at C-2 and C-4 are sensitive to nucleophilic displacement by an addition-elimination mechanism. There is a parallel to the reaction of imino halides and acyl halides (see Scheme 4.27a). There are a number of other parallels to carbonyl chemistry. Thus a methyl group at C-2 or C-4 undergoes condensation reactions (Scheme 4.27b) and an acetic acid residue at C-2 undergoes decarboxylation (Scheme 4.27c). 

In unsaturated aliphatic systems the most important reactions are those of czirbonyl compounds of the type —COX, in which X is a good leaving group such as halogen. In general, most displacement reactions of anionic nucleophiles on the carbonyl carbon atom of acyl halides involve an addition-elimination mechanism " (e.g. equation 16). In such reactions bond-formation is in advance of bond-rupture... 

By careful investigation of the reaction between acyl halides and chlorotris(triphenylphosphine) rhodium, we found that a new acylrho-dium complex (XIII) could be isolated in good yield. It forms by the oxidative addition of acyl halide, with the elimination of one mole of triphenylphosphine (25). This is the first example of acyl complex formation by direct oxidative addition of acyl halides. 

In their zerovalent compounds, all three metals (Ni, Pd, Pt) undergo oxidative addition of alkyl, aryl, and acyl halides. For palladium, in particular, such reactions are key steps in a wide range of catalytic reactions. Palladium(II) and platinum(II) complexes also add C—X bonds to generate Pd(IV) and Pt(IV) species. Since C—C or C—H bond formation by reductive elimination often occurs readily, a common reaction sequence involves C—X addition followed by coupling of two alkyl groups, or an alkyl and a hydride ligand. 

Particular attention has been devoted to oxidative addition and reductive elimination reactions of [M2(PNNP)(/x-X)L2] with acyl and alkyl halides. Depending on the electron richness of the metals, a complete spectrum of possibilities was observed from reversible single oxidative addition on one of the metals to irreversible double oxidative addition on both metals (2) (Scheme 12). 

With a Ni(cot)2 catalyst in a polar solvent, carbon monoxide is evolved and the stan-nane R3SnR is formed, presumably by oxidative addition to give R3SnNinCOR then elimination of CO followed by reductive elimination, and they react with acyl halides in the presence of a palladium(II) catalyst to give the corresponding a-diketones.65 Reactions of potential synthetic use have been developed, in which oxidative addition is followed by insertion of an electron-rich66 or electron-poor alkyne,67 or of a 1,2-68 or 1,3-diene,69 or of an enone.67 Typical reactions and reaction conditions are shown in Table 6-2. 

Examples of addition reactions of tributyltin methoxide are given in Table 14-3. Most of these reactions are reversible for example, the alkyl tin carbonate which is formed by the addition of a tin alkoxide to carbon dioxide eliminates C02 on heating to regenerate the tin alkoxide (equation 14-14). Again, the product of the reaction of an acyl halide with a dioxastannolane is involved in an exchange reaction in which the tin alkoxide adds reversibly to the carbonyl group (equation 14-31).41... 

Another modification, involving a destannylation, gave cyclopropane 12. In this case, treatment of a but-3-en-l-yistannane with an electrophilic reagent gave initially the addition product 11 which then underwent 1,3-elimination. In a similar manner, reaction of (but-3-en-l-yl)trimethylsilane with an acyl halide gave cyclopropyl ketones 13. ... 

The classical Hofmann elimination reaction (which dates back to 1851) has been adapted to the solid phase in combination with the Michael addition. The REM resin, called this way because the resin tinker is REgenerated after product cleavage and functionalized by means of a Michael addition, has been developed to prepare arrays of tertiary amines. The procedure involves acylation of hydroxy-methylpolystyrene with acrylic chloride to furnish the acrylate on resin. Then, a secondary amine, whose substituents offer two potential sites of diversity, is bound by Michael addition. Quaternization of the amine with an alkyl halide (or reductive animation) introduces another site of diversity and activates the tinker to release the amine by a Hofmann elimination with DIEA (Figure 15.14) [127-129]. Additionally, the use of a second basic resin has been described as a source reagent to promote the elimination [130, 131]. 

In the foregoing, the formation of organic molecules on transition metal complexes is explained by stepwise processes of oxidative addition, insertion, and reductive elimination. One typical example, which can be clearly explained in this way, are the carbonylation and decarbonylation reactions catalyzed by rhodium complexes 10-137). Tsuji and Ohno found that RhCl(PPh3)3 decarbonylates aldehydes and acyl halides under mild conditions stoichiometrically. Also this complex and RhCl(CO) (PPh3)2 are active for the catalytic decarbonylation at high temperature. 

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