Positional selectivity formylation

Benzodipyrrole 1 is selectively formylated at the 3- and 6-positions by a Vilsmeier-Haack reaction to produce 3,6-diformylbenzodipyrrole which is reduced by lithium aluminium hydride to give 3,6-dimethylbenzodipyrrole. This can also undergo subsequent Vilsmeier-Haack formylation to afford the 2,5-dialdehyde (Scheme 2) <2005AGE4053>. 

Although /V-methyltetrahydropyridines are not selectively hydroformylated, an equal mixture of the two aldehydes being obtained from /V-methy 1-1,2,3,6-tetrahydropyridine, W-methyltropidenes are selectively formylated at the 3-position (equation 29). The difference in the selectivity can be attributed to the substitution in tropidine (bridge head carbon). 

These substitutions are facilitated by electron release from the heteroatom pyrroles are more reactive than furans, which are in turn more reactive than thiophenes. Quantitative comparisons of the relative reactivities of the three heterocycles vary from electrophile to electrophile, but for trifluoroacetylation, for example, the pyrrole furan thiophene ratio is 5 x 10 1.5 x 10 I " in formylation, furan is 12 times more reactive than thiophene, and for acetylation, the value is 9.3. In hydrogen exchange (deuteriodeproton-ation), the partial rate factors for the a and p positions of A-methylpyrrole are 3.9 x 10 ° and 2.0 x 10 ° respectively for this same process, the values for furan are 1.6 x 10 and 3.2 x l(f and for thiophene, 3.9 X 10 and 1.0 x 10 respectively, and in a study of thiophene, a P ratios ranging from 100 1 to 1000 1 were found for different electrophiles. Relative substrate reactivity parallels positional selectivity i.e. the a P ratio decreases in the order furan > thiophene > pyrrole. ° Nice illustrations of these relative reactivities are found in acylations of compounds containing two different systems linked together. ... 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

Still another route for selective formylation makes use of the tricarbonyl-chromium complexes of calix[4]arenes. Reaction of the tetrapropyl ether of 4 with Cr(CO)3 produces a complex in which a Cr(CO)3 moiety is associated with a single aromatic residue of the calixarene. Treatment of the complex with BuLi and then D2O, Mel, or DMF followed by decomplexation with I2 yields mono-substituted calix[4]arenes carrying D at a p- or m-position. Me at a p-position, and CHO at a p-position, respectively." ... 

ABSTRACT. Selective formylation of phenol at the 4-position is achieved by using 3-cyclodextrin as catalyst in the reaction of phenol with chloroform in aqueous alkali. The reactions of 1,3-dihydroxybenzene and indol, respectively, in the place of phenol give 2,4-dihydroxybenz-aldehyde and indole-3-aldehyde in virtually 100% selectivies and high yields. The reactions of para-substituted phenols, 4-methylphenol and 5,6,7,8-tetrahydro-2-naphthol, instead of phenol, effect the selective dichloromethylation at the para-positions. Selective carboxylation of phenol at the 4-position is achieved in the reaction of phenol with carbon tetrachloride in aqueous alkali by using 3-cyclodextrin and copper powder as catalyst. 

In contrast to la the reaction of lb proceeded with high positional selectivity affording the 4-formylated product 6 (96%) together with a small amount of by-product 2-formyl-1-methyl-naphthalene 7 (4%) (Table 6 Run 2). The formylation of Id under similar conditions produced the 3-formylated compound 10 exclusively in high yield (Table 1.6 Run 4). 

Cieplak apphed this effect to the explanation of the shift of selectivity in the reactions of the pentamethylcyclopentadienes 21,19, and 20 having substiments of formyl, vinyl, and (hydroxyimino)methyl moiety at the 5-positions [14]. He pointed out that the observed result is consistent with the notion that in the case of formyl moiety the hyperconjugative effect is enhanced by lone pair back-donation due to ... 

We next contemplated whether the unsaturation site could be encompassed in the context of a properly positioned benzo linkage. We were intrigued to discover that excellent diastereoface selectivity was obtained in the aldol condensation of the Z-lithium enolate with the benzyl-substituted formyl moiety, entry g. 

Extending their earlier work on Vilsmeier formylation (c/. Vol. 7, p. 36), Traas et al. have formylated the a/S-unsaturated ketone isophorone almost exclusively at the more favoured exocyclic position to yield (190), which may be selectively... 

In the presence of Co2(CO)8, selectivity seems to depend on the number and relative position of the double bond substituents as well as on the reaction temperature. As is usually the case with Co2(CO)8, hydro-formylation leads mainly to the least branched aldehydes when the carbon a to the ring bears two substituents. However, when this carbon is monosubstituted, the ring effect becomes more important and CO insertion occurs on the benzylic position. 

Other Cig-fatty acids have also a high potential in hydroformylation, such as ricinoleic acid, which contains an additional hydroxy group at position 12 of the fatty carbon chain and which is not food relevant [26], The hydroformylation of ethyl ricinoleate, derived from castor oil, shows selectivity for cyclization of the carbon chain because of the reaction of the hydroxyl group with the formyl group (Scheme 8). 

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