Inductive effects, carbonyl compounds

Fluorinated Acids. This class of compounds is characterized by the strength of the fluorocarbon acids, eg, CF COOH, approaching that of mineral acids. This property results from the strong inductive effect of fluorine and is markedly less when the fluorocarbon group is moved away from the carbonyl group. Generally, their reactions are similar to organic acids and they find apphcations, particularly trifluoroacetic acid [76-05-1] and its anhydride [407-25-0] as promotors in the preparation of esters and ketones and in nitration reactions. 

As a consequence of the pericyclic reaction path, the addition of a-stereogenic allylmctals to carbonyl compounds is accompanied by an effective 1,3-chirality transfer in the allylic moiety combined with 1,4-chira induction at the prostereogenic carbonyl group3032. The scheme also demonstrates the importance of the orientation of the substituent X in the six-membered transition state. By changing from a pseudo-axial to a pseudo-equatorial position, the cation-induced sy/i-attack addresses opposite faces of both prostereogenic moieties, leading to a Z-and an -isomer, these being enantiomeric in respect to the chiral moiety. 

Delocalisation takes place (cf. 1,3-dienes, p. 13), so that an electron-deficient atom results at C3, as well as at C, as in a simple carbonyl compound. The difference between this transmission via a conjugated system, and the inductive effect in saturated system, is that here the effect suffers much less diminution by its transmission, and the polarity at adjacent carbon atoms alternates. 

One problem in the anti-selective Michael additions of A-metalated azomethine ylides is ready epimerization after the stereoselective carbon-carbon bond formation. The use of the camphor imines of ot-amino esters should work effectively because camphor is a readily available bulky chiral ketone. With the camphor auxiliary, high asymmetric induction as well as complete inhibition of the undesired epimerization is expected. The lithium enolates derived from the camphor imines of ot-amino esters have been used by McIntosh s group for asymmetric alkylations (106-109). Their Michael additions to some a, p-unsaturated carbonyl compounds have now been examined, but no diastereoselectivity has been observed (108). It is also known that the A-pinanylidene-substituted a-amino esters function as excellent Michael donors in asymmetric Michael additions (110). Lithiation of the camphor... 

Since tJtiis reaction is an equilibrium, the amount of cyanohydrin formed from any given carbonyl compound will depend on the relative stabilities of the carbonyl compound itself and the product. There can be many substituents X on a carbonyl compound R.CO.X, such as Cl, Me, NH2, Ph, OEt, H. Some have inductive effects, some conjugate with the carbonyl group. Some stabilise RCOX making it less reactive. Others activate it towards nucleophilic attack. Arrange the compounds RCOX, where X can be the substituents listed above, into an order of reactivity towards a nucleophile. 

Substituents with a electron-donating inductive (+1) effect (i.e., alkyl groups) stabilize the C=0 double bond of aldehydes and ketones. They increase the importance of the zwitterionic resonance form by which carbonyl compounds are partly described. The driving force for the formation of addition products from carbonyl compounds therefore decreases in the order H—CH(=Q) > R—CH(=0) > R R2c(=0). 

Acetic acid is a stronger acid than ethanol by a factor of about 10. In both compounds the acidic hydrogen is bonded to an oxygen. Replacing the CH2 of ethanol with a C=0 results in an enormous increase in acidity. Part of this increase is due to the inductive effect of the oxygen of the carbonyl group, but the effect is much too large to be due only to this. 

The equilibrium in these reactions may favor the products or the reactants, depending on the strength of the nucleophile and the structure of the carbonyl compound. Stronger nucleophiles shift the equilibrium toward the products, and very strong nucleophiles give an irreversible reaction, that is, one that proceeds in only one direction, from the reactants to the products. The structure of the aldehyde or ketone exerts its influence through resonance, steric, and inductive effects, as usual. It is easiest to see these effects in examples, so let us proceed to examine some of the nucleophiles that can be used in these addition reactions. 

Because the equilibrium constants are neither too large nor too small, the hydration reaction provides an excellent opportunity to examine the effect of the structure of the carbonyl compound on the equilibrium constant. Let s consider inductive effects first. 

Data for aliphatic aldehyde enolisation are very scarce, probably because the enolisation process is often complicated by oxidation and hydration. Nevertheless, the rate constants for base- and acid-catalysed iodination of R R2CHCHO were determined in aqueous chloroacetic acid-chloroacetate ion buffers (Talvik and Hiidmaa, 1968). The results in Table 4 show that alkyl groups R1 and R2 increase the acid-catalysed reactivity in agreement with hyperconjugative and/or inductive effects. This contrasts with aliphatic ketones for which steric interactions are important and even sometimes dominant. Data for base-catalysis are more difficult to interpret since a second a methyl group, from propionaldehyde to isobutyraldehyde, increases the chloroacetate-catalysed rate constant. This might result from a decrease of the a(C—H) bond-promoted hyperconjugative stabilisation of the carbonyl compound... 

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