Formylation of Organic Halides

The synthesis of aromatic aldehydes from aryl halides, carbon monoxide, and a hydride source has also been studied, but practical procedures for this process have been published only recently. Thus, the presentation of this process will be brief. The original formyla-tions of aryl halides were conducted with a tin hydride, as shown in Equation 19.88, or a silicon hydride. More recently, reactions were reported with formate as the hydride source (Equation 19.89). In fact, one of the earliest palladium-catalyzed reactions of aryl chlorides was the fonnylation of an aryl chloride to form aromatic aldehydes using 

Examples of the formylation of aryl halides with synthesis gas catalyzed by palladium complexes are summarized in Equation 19.90. These reactions relied upon the development of ligands with particular steric and electronic properties. The dia-damantyl-n-butyl phosphine shown in the equation, in combination with palladium acetate, leads to the formation of aromatic aldehydes in high yields from electron-rich and electron-poor aryl bromides. Reactions of nitroarenes and 2-bromopyridine provided the aldehydes in low yield, but other examples occurred in satisfactor) yield with only 0.1-0.75 mol % catalyst. The identity of the base is important in this process, and TMEDA was the most effective base. The mechanism of this process was not proposed in the initial work, but is likely to occur by oxidative addition of the aryl halide, insertion of the carbon monoxide into the palladium-aryl bond, and a combination of hydrogenolysis of the acyl intermediate and elimination of hydrogen halide to regenerate palladium(O). The base would then be involved in the hydrogenol5 sis and consumption of hydrogen halide. 

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Baillargeon, V. P., Stille, J. K. Palladium-catalyzed formylation of organic halides with carbon monoxide and tin hydride. J. Am. Chem. Soc. 1986, 108,452 61. 

A more versatile palladium-catalyzed formylation of organic halides takes place using tributyltin hydride and carbon monoxide (equation 7). The reaction works for a variety of substrates — aryl, benzyl and vinyl iodides, vinyl triflates and allyl halides. Reaction conditions are mild (1-3 bar CO, 50 °C), and a variety of functional groups can be tolerated. With unsymmetrical allyl halides formylation is regio-selective, taking place at the less-substituted allylic position with retention of geometry at the allylic double bond. 

Formate salts [69] or formic add under conditions converting them electrodiemically into formate [70,71], sUyl, and tin hydrides have been also explored to perform formylations of organic halides/triflates under lower pressure of carbon monoxide. Acetic formic anhydride has been used as a source of carbon monoxide for the conversion of aryl iodides in conjunction with RsSiH [72]. The palladium-catalyzed formylation of a wide variety of vinyl iodides and triflates with tin hydride and carbon... 

Formylation reactions of organic halides, palladium-catalyzed, 26 330, 331 Fouling, 26 378... 

In a useful application, Kahne and Gupta reported the radical hydroxymethyla-tion (formylation and in situ reduction) of organic halides, including sugar derivatives, using a catalytic amount of triphenylgermyl hydride in the presence of so-... 

Alkyl halides do not fonnylate due to the propensity of the palladium species to undergo /3-hydride ehmination. The conversion of organic halides containing a /3-hydride to the methyl ketone was reported using tetramethyltin, but no mention of formylation has followed to the best of our knowledge. " Methyl alcohol was converted to acetaldehyde using a mixed catalyst system of CO and hi an earher report the acylpalladium... 

Staab introduced azolides as versatile reagents in organic synthesis. The reaction of carbonyldiimid-azolide with carboxylic acids produces imidazolides under mild conditions which can be converted by the action of hydrogen halides to acid halides in high yield (equation 20). The method does not even require the isolation of the imidazolides, but can be carried out as a one-pot synthesis. The possibility of carrying out this reaction at low temperatures allows the preparation of temperature sensitive compounds. Formyl chloride, which decomposes at -40 °C, has been prepared in this way. 

Hydroxymethylation. Organic halides undergo radical carbonylation and in the presence of NaBHjCN the formyl group is reduced in situ. 

A variety of carbonyl compounds can be prepared, using tin hydride as a radical mediator. Table 1 illustrates examples of radical formylation of several organic halides. The reaction can be applied to aromatic formylation [18] but not to stable radicals such as allyl, benzyl, alkoxymethyl, a-cyanoalkyl, and a-acylalkyl radicals. 

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