Aldehydes carbonyl group, addition

Aldol Addition and Related Reactions. Procedures that involve the formation and subsequent reaction of anions derived from active methylene compounds constitute a very important and synthetically useful class of organic reactions. Perhaps the most common are those reactions in which the anion, usually called an enolate, is formed by removal of a proton from the carbon atom alpha to the carbonyl group. Addition of this enolate to another carbonyl of an aldehyde or ketone, followed by protonation, constitutes aldol addition, for example... 

Q Addition to the ketone or aldehyde carbonyl group by the neutral amine nucleophile gives a dipolar tetrahedral intermediate. 

Just as the Kiliani-Fischer synthesis lengthens an aldose chain by one carbon, the Wohl degradation shortens an aldose chain by one carbon. The Wohl degradation is almost the exact opposite of the Kiliani-Fischer sequence. That is, the aldose aldehyde carbonyl group is first converted into a nitrile, and the resulting cyanohydrin loses HCN under basic conditions—the reverse of a nucleophilic addition reaction. 

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 reacting aldehyde displaces the oxazolidinone oxygen at the tetravalent boron in the reactive TS. The conformation of the addition TS for boron enolates is believed to have the oxazolidinone ring oriented with opposed dipoles of the ring and the aldehyde carbonyl groups. 

It is proposed that the reaction proceeds through (i) oxidative addition of a silylstannane to Ni(0) generating (silyl)(stannyl)nickel(n) complex 25, (ii) insertion of 1,3-diene into the nickel-tin bond of 25 giving 7r-allylnickel intermediate 26, (iii) inter- or intramolecular allylation of aldehydic carbonyl group forming alkoxy(silyl)nickel intermediate 27, and (iv) reductive elimination releasing the coupling product (Scheme 69). 

Tandem procedures under hydroformylation conditions cannot only make use of the intrinsic reactivity of the aldehyde carbonyl group and its acidic a-position but they also include conversions of the metal alkyl and metal acyl systems which are intermediates in the catalytic cycle of hydroformylation. Metal alkyls can undergo -elimination leading to olefin isomerization, or couplings, respectively, insertion of unsaturated units enlarging the carbon skeleton. Similarly, metal acyls can be trapped by addition of nucleophiles or undergo insertion of unsaturated units to form synthetically useful ketones (Scheme 1). 

A variation of GTP, referred to as aldol GTP, involves polymerization of a silyl vinyl ether initiated by an aldehyde [Sogah and Webster, 1986 Webster, 1987]. Both initiation and propagation involve nucleophilic addition of the vinyl ether to the aldehyde carbonyl group with transfer of the trialkyl silyl group from vinyl ether to the carbonyl oxygen (Eq. 5-82). The reaction has similar characteristics as GTP. The product is a silated poly(vinyl alcohol) (PVA), which can be hydrolyzed by acid to PVA (Eq. 5-83). 

The reduction of carbonyl compounds with metal hydride reagents can be viewed as nucleophilic addition of hydride to the carbonyl group. Addition of a hydride anion to an aldehyde or ketone produces an alkoxide anion, which on protonation gives the corresponding alcohol. Aldehydes give 1°-alcohols and ketone gives 2°-alcohols. 

Similarly, when the substituted salicylaldehydes 5 were reacted with the (Z)-/ -nitrostyrenes 6, a variety of dihydrobenzopyrans rac-1 were obtained diastereomerically pure in 41-80% yield58. Note that the products rac-1, bearing three stereocenters, arise from an additional diastereoselective addition of the intermediate nitronate anion to the aldehyde carbonyl group. Again, the relative configuration of the product(s) is in accord with a thermodynamically controlled reaction. 

Chemically analogous transformations occur enzymatically. For example, in the glycolase system glutathione (34 GSH, Glu-Cys-Gly) catalyzes the conversion of methylglyoxal (33) to lactic acid (35), as shown in equation (20). This transformation is initiated not by hydroxide, but by the addition of thiolate from GSH to the aldehyde carbonyl group. ... 

Rigidified binuclear zinc chelates are formed, and their asymmetry promotes the facial diastereodifferentiation of the aldehyde carbonyl group in a highly enantiose-lective reaction ( 2.5.1,6.5.1). Chiral aminoalcohols and diamines are the most efficient ligands to promote asymmetric conjugate additions of lithio- or magne-siocuprates to a,p-unsaturated carbonyl compounds [112] ( 7.10.1). 

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