Carboxenium ion

A combined experimental and computational approach has been undertaken to identify the origin of syn/anti diastereoselectivity in two types of crotylation reactions of aldehydes and ketones (i) multi-component crotylations of simple aldehydes/ketones and (ii) acetal substitution reactions of aldehyde dimethyl acetals with E- and Z-configured crotyltrimethylsilane.175 The stereochemical outcome is nearly identical in the two reactions, and the computational results suggest that this is due to near identical mechanisms an SN1 process involving attack of O-methyl-substituted carboxenium ions by crotylsilane. 

High levels of enantioselectivity are achieved when the stereochemistry-inducing group is fixed in the transition state, thereby preventing one side of the molecule from attacking the carboxenium ion. Because of steric and electronic effects, the crotyl silane confor-m ations are stabilized when the dihedral angle between the C-Si bond and the ally lie double bond is about 120°. This structural element is still relevant in the transition state of the attack of 12 to a carboxenium ion such as 4 or 8. Therefore, attack cannot come fi om conformation III, but only from conformations I or II. Conformation II, however, is disfavored over conformation I because of 1,3-allylic strain. The bulky silyl group in conformation I then demands that the attack to the electrophile comes from the opposite si face. 

The carboxenium ion formed from the elimination of water of the intermediate hemiacetal has acidic hydrogens in the a-position. 

The reaction follows the general mechanism for the acetalization of a ketone but yields the hemiacetal elimination product 18. After activation of the secondary ketone 17 by protonation, nucleophilic attack of methanol yields the protonated hemiacetal 30. Deprotonation and protonation of the alcohol moiety provides species 32, which eliminates water to give the carboxenium ion 33. 

In normal acetalization reactions, this carboxenium ion is once again attacked by methanol to yield the dimethyl acetal 34. Here, however, elimination can occur owing to the ester group in P-position, which (a) makes the hydrogen atoms in a-position more acidic and therefore better leaving groups, and (b) stabilizes the elimination product 18 by conjugation. Thus, an /Z-mixture of 18 in a 7 1 ratio is obtained. 

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See also in sourсe #XX -- [ ]

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