Carbonyl groups, 40. protonation

Now use the negatively charged a carbon of the enolate to form a new carbon-carbon bond to the carbonyl group Proton transfer from the solvent completes the process... 

This pattern of increased reactivity resulting from carbonyl group protonation has been seen before in nucleophilic additions to aldehydes and ketones (Section 17.6) and... 

The acid-catalyzed hydration is a typical acid-catalyzed addition to the carbonyl group. Protonation, followed by addition of water, gives a protonated product. Deprotonation gives the hydrate. 

Under basic conditions, the aldol condensation occurs by a nucleophilic addition of the enolate ion (a strong nucleophile) to a carbonyl group. Protonation gives the aldol product. 

Under strongly acidic conditions, a C —C double bond can substitute the carbonyl group. Protonation of the endocyclic double bond in bicyclo[4.1.0]hept-3-ene 12 by trifluoroacetic acid renders the cyclopropane ring susceptible to the intramolecular nucleophilic attack by a carboxylate group generated in situ. ... 

This pattern of increased reactivity resulting from carbonyl group protonation has been seen before in nucleophilic additions to aldehydes and ketones (Section 17.6) and in the mechanism of the acid-catalyzed esterification of carboxylic acids (Section 19.14). Many biological reactions involve nucleophilic acyl substitution and are catalyzed by enzymes that act by donating a proton to the carbonyl oxygen, the leaving group, or both. 

This molecule is truly appealing because a nucleophile is expected to add on to the boron atom before any addition to the carbonyl carbon to give 22 (Fig. 9) [16]. This is so because the boron atom is >1.5 times more electron-deficient than the carbonyl carbon. This will have consequences on the observed selectivity. On using hydride ion as the nucleophile to add to boron and H+ for carbonyl group protonation, D2 is discovered to be >40° larger than D1 and, hence, an eminent equatorial attack [17]. This analysis is in agreement with the result observed for... 

Neutral carbonyl group Protonated carbonyl group... 

Thionane (15) forms a number of crystalline derivatives a mercury addition compound (m.p. 92-93°C), the sulfone (m.p. 81.5-82°C) and the methiodide (m.p. 124-124.5°C). With excess iodo-methane in a sealed tube, 1,9-diiodooctane is formed <53M1206>. While the IR spectrum of thionan-5-one (143) shows no evidence for a transannular interaction between the sulfur lone electron pairs and the carbonyl group, protonation with perchloric acid leads to the bicyclic sulfonium salt (144) (Scheme 11) <62JA2814>. 

Under basic conditions, the aldol condensation occurs by a nucleophilic addition of the enolate ion (a strong nucleophile) to a carbonyl group. Protonation gives the aldol product. Note that the carbonyl group serves as the electrophile that is attacked by the nucleophilic enolate ion. From the electrophile s viewpoint, the reaction is a nucleophilic addition across the carbonyl double bond. From the viewpoint of the enolate ion, the reaction is an alpha substitution The other carbonyl compound replaces an alpha hydrogen. 

A nucleophile can attack an a,)8-unsaturated carbonyl compound at either the carbonyl group or at the (3 position. When attack occurs at the carbonyl group, protonation of the oxygen leads to a 1,2-addition product in which the nucleophile and the proton have added to adjacent atoms. When attack occurs at the (3 position, the oxygen atom is the fourth atom counting from the nucleophile, and the addition is called a 1,4-addition. 

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