Aldehydes from 1-acylimidazoles

Aldehydes from carboxylic acids via 1-acylimidazoles s. 18, 127 COOH CHO... 

Aldehydes and Ketones from Carboxylic Acids. Reduction of the derived acylimidazole (2) with Lithium Aluminum Hydride achieves conversion of an aliphatic or aromatic carboxylic acid to an aldehyde (eq 6). Diisobutylaluminum Hydride has also been used, allowing preparation of a-acylamino aldehydes from iV-protected amino acids. Similarly, reaction of (2) with Grig-nard reagents affords ketones, with little evidence for formation of tertiary alcohol. 

Much work in the review period has concerned enantioselective substitution in five-membered heterocyclics. The enantioselective alkylation of some pyrroles by unsaturated 2-acylimidazoles catalysed by the bis(oxazolinyl)pyridine-scandium(in) triflate complex (31) has been reported.39 Compound (33) is formed in 98% yield and 94% ee from the 2-acylimidazole (32) and pyrrole at —40 °C. A series of enantiomer- ically pure aziridin-2-ylmethanols has been tested as catalysts in the alkylation of /V-mclhylpyrrolc and (V-methylindole by ,/l-unsalura(cd aldehydes.40 Enantiomeric excesses of up to 75% were observed for the alkylation of /V-mcthylpyrrole by ( >crotonaldehyde using (2.S ,3.S )-3-mclhylazirin-2-yl(diphenyl)methanol TFA salt as catalyst to form (34). 

Peracids can also be prepared from reaction of hydrogen peroxide with acyl halides, anhydrides, amides, dialkyl phosphates, N-acylimidazoles, aromatic aldehydes, lipase catalysis and esters (Figure 2.38).100-107... 

The synthesis of aldehydes [C5] can also be accomplished by controlled reduction of acylaziridines 3.178 [BK5] or of acylimidazoles 3.179 [W3] by LAH in Et20 at -10°C, by LTBA or by Red-A1 in [H3, M3] R can be aliphatic or aromatic (Figure 3.66). The N-methoxy-N-methylcarboxamides 3.180 are also cleanly reduced to aldehydes by LAH in excess in THF at low temperature or by DIBAH in THF at 0°C. In many cases, the latter reagent does not lead to formation of alcohols as byproducts resulting from a subsequent reduction of the aldehyde [NWl]. This behavior can be understood by the stabilization through chelation of the lithium or aluminum intermediate (Figure 3.66). a,p-Unsaturated aldehydes may also be prepared by this method, using DIBAH in THF [BS8, NBl]. 

Ried et ah551 recently found a generally applicable aldehyde synthesis in the hydrogenolytic fission of l-acyl-3,5-dimethylpyrazole by lithium aluminum hydride, a reaction that takes place with very good yields in ether at 0-20°. An appreciably better method still is to use the same hydride in ether or tetrahydrofuran to reduce the corresponding 1-acylimidazoles, which are readily obtained from the free acids and l,l -carbonyldiimidazole with 0.25 mole of hydride per mole of acylimidazole the reduction is complete in 30-60 min at —20°,552 and it is an advantage of the method that it can be carried out entirely in one vessel without isolation of the acylimidazole intermediate. 

A-Acylimidazoles are even more easily hydrolysed than A-acylpyrroles, moist air is sufficient. The ready susceptibility to nucleophilic attack at carbonyl carbon has been capitalised upon commercially available I,r-carbonyldiimida-zole (CDI), prepared from imidazole and phosgene, can be used as a safe phosgene-equivalent, i.e. a synthon for 0=C, and also in the activation of acids for formation of amides and esters via the A-acylimidazole. In another application, A-acylimidazoles react with lithium aluminium hydride at O C to give aldehydes, providing a route from the acid oxidation level. 

Acylimidazoles and Nucleophiles. Acylimidazoles are readily prepared from the parent carboxylic acids by reaction of the derived acid chloride with imidazole or directly using N,N -Carbonyldiimidazole. These intermediates react smoothly with a variety of nucleophiles including Grignard reagents (eq 3), Lithium Aluminum Hydride (eq 4), and nitronates (eq 5). At —20 ""C, aroylimidazoles can be reduced to the corresponding aldehydes in the presence of an ester function. ... 

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