Carbonyl group base-catalyzed addition

CYANOHYDRINS. A cyanohydrin is an organic compound that contains both a cyanide and a hydroxy group on an aliphatic section of the molecule. Cyanohydrins are usually a-hydroxy nitriles which are the products of base-catalyzed addition of hydrogen cyanide 10 the carbonyl group of aldehydes and ketones. The IUPAC name for cyanohydrins is based on the or-hydroxy nitrile name. Common names of cyanohydrins are derived from the aldehyde or ketone from which they arc formed. 

In effect, the base-catalyzed addition to a carbonyl group results from nucleophilic attack of a strong nucleophile followed by protonation. Acid-catalyzed addition begins with protonation, followed by the attack of a weaker nucleophile. Many additions are reversible, with the position of the equilibrium depending on the relative stabilities of the reactants and products. 

The base-catalyzed hydration is a perfect example of base-catalyzed addition to a carbonyl group. The strong nucleophile adds, then protonation gives the hydrate. 

In a broader context, but based on his own investigations of general acid- and based catalyzed additions to carbonyl groups, Jencks classifies a reaction like the azo coupling of l-naphthol-3-sulfonic acid dianion catalyzed by water molecule(s) hydrogen-bonded at the naphtholate oxygen as a pre-association mechanism. 

The base-catalyzed mechanism (Bac2) proceeds via the direct nucleophilic addition of OH" to the carbonyl group. Base catalysis occurs because hydroxide ion is a stronger nucleophile than water. 

Scheme 937. A representation of the steps in base-catalyzed addition of cyanide (CN ) anion across the carbonyl (C=0) group. Addition to either face re or si) of the carbonyl is...

FIGURE 16.89 Base-catalyzed additions to carbonyl groups. 

Mechanism 21.7 Base-Catalyzed Addition of H2O to a Carbonyl Group... 

Imine Formation from an Aldehyde or Ketone 798 Enamine Formation from an Aldehyde or Ketone 800 Base-Catalyzed Addition of H2O to a Carbonyl Group 803 Acid-Catalyzed Addition of H2O to a Carbonyl Group 803 Acetal Formation—Part [1] Formation of a Hemiacetal 806 Acetol Formation—P ferma n of the Acetal 806... 

Conjugation of the newly formed double bond with the carbonyl group stabilizes the a p unsaturated aldehyde provides the driving force for the dehydration and controls Its regioselectivity Dehydration can be effected by heating the aldol with acid or base Normally if the a p unsaturated aldehyde is the desired product all that is done is to carry out the base catalyzed aldol addition reaction at elevated temperature Under these conditions once the aldol addition product is formed it rapidly loses water to form the a p unsaturated aldehyde... 

Alditol (Section 25 18) The polyol obtained on reduction of the carbonyl group of a carbohydrate Aldol addition (Section 18 9) Nucleophilic addition of an aldehyde or ketone enolate to the carbonyl group of an aide hyde or a ketone The most typical case involves two mole cules of an aldehyde and is usually catalyzed by bases... 

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

N-Acetylneuraminic acid aldolase (or sialic acid aldolase, NeuA EC 4.1.3.3) catalyzes the reversible addition of pyruvate (2) to N-acetyl-D-mannosamine (ManNAc (1)) in the degradation of the parent sialic acid (3) (Figure 10.4). The NeuA lyases found in both bacteria and animals are type I enzymes that form a Schiff base/enamine intermediate with pyruvate and promote a si-face attack to the aldehyde carbonyl group with formation of a (4S) configured stereocenter. The enzyme is commercially available and it has a broad pH optimum around 7.5 and useful stability in solution at ambient temperature [36]. 

The Ru-catalyzed cyclocarbonylation of a-allenic sulfonamides proceeds in the presence of Et3N under a CO atmosphere (20 atm) to yield ,/funsaturated lactams (Scheme 16.32) [36], In order to gain an insight into the reaction mechanism, a deuterium-substituted a-allenic sulfonamide was subjected to the carbonylation. The deuterium was found to be totally transferred to the methyl group. Based on this observation, a mechanism has been proposed which involves a ruthenacycle derived from addition of the Ru-H to the terminal double bond of allene (Scheme 16.33). 

In HO -catalyzed hydrolysis (specific base catalyzed hydrolysis), the tetrahedral intermediate is formed by the addition of a nucleophilic HO ion (Fig. 3.1, Pathway b). This reaction is irreversible for both esters and amides, since the carboxylate ion formed is deprotonated in basic solution and, hence, is not receptive to attack by the nucleophilic alcohol, phenol, or amine. The reactivity of the carboxylic acid derivative toward a particular nucleophile depends on a) the relative electron-donating or -withdrawing power of the substituents on the carbonyl group, and b) the relative ability of the -OR or -NR R" moiety to act as a leaving group. Thus, electronegative substituents accelerate hydrolysis, and esters are more readily hydrolyzed than amides. 

Asymmetric addition of small-molecule nucleophiles to carbonyl groups and their derivatives are catalyzed by either Lewis acids or Lewis bases. Carbon dioxide is now a promising building block for as5mimetric organic synthesis. 

The mechanism of the base-catalyzed reaction involves equilibrium formation of the enolate ion, followed by addition of the enolate to a carbonyl group of the aldehyde or ketone. 

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