Ketones 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... 

Welch s stereoselective synthesis centered about the tandem conjugate addition of a methyl group and allylation to produce 583 (Scheme XLVI). A second methylation, combined with oxidation of the allyl sidechain, gave 584 which was successfully cyclized under Claisen conditions. Trapping of the enolate as in 585 permitted differentitation between the two potential ketone carbonyl groups. 

Reconversion of the ketonic carbonyl group into a diazo group sets the stage for intramolecular carbenoid addition to an alkene [276]. A recent paper described syntheses of 2-C-trifluoromethyl 3-deoxypentoses [277] from ethyl trifluoropyru-vate other approaches to heterocycles containing trifluoromethyl groups were reviewed recently and will therefore not be discussed further here [278]. 

Acid Catalyzed. Although ketonic carbonyl groups are less reactive than aldehydic carbonyls in the presence of basic catalysts, this is not the case with acid catalysts. Thus acetone undergoes aldol addition in the presence of sulfuric acid to give mesityl oxide, which then condenses with a third molecule of acetone to give a mixture ofphorone (2,6-dimethyl-2,6-heptadien-4-one) and mesitylene (1,3,5-trimethylbenzene). Ketones also condense with activated aromatic products in the presence of sulfuric acid to give coupled aromatic products. For example, acetone and phenol condense to bisphenol A (4,4 -isopropylidenediphenol), which is used in the manufacture of epoxy resins (qv) and polycarbonates (qv). 

In (C5Me5)Rh(C2H3SiMe3)2-catalyzed C-H/olefin coupling the effect of the coordination of the ketone carbonyl is different from that in the ruthenium-catalyzed reaction [10], In the rhodium-catalyzed reaction all C-H bonds on the aromatic ring are cleaved by the rhodium complex without coordination of the ketone carbonyl. Thus, C-H bond cleavage and addition of Rh-H to olefins proceed without coordination of the ketone carbonyl. After addition of the Rh-H species to the olefin, a coordinatively unsaturated Rh(aryl) (alkyl) species should be formed. Coordination of the ketone carbonyl group to the vacant site on the rhodium atom leads... 

A stereoelectronic argument (62) would suggest quasi-axial addition leading to the right configuration (XLIV) for dihydrostrychninonic acid. The reduction of strychninonic acid to the epimeric strychninolic acid is governed simply by the more ready accessibility of the outer side of the ketone carbonyl group (62). 

The key fdep in this biotoigicai traiufiirmatitm is the nueieopbiKc addition of ati amine to the ketone carbonyl group of pyruvic acid. The tetca hedral intermediate loses water to yield an itnine, which is further reduced in a second nucleophilic addition step to yield alanine. 

Addition of thiamine. The conversion of pyruvate to acetyl CoA begins by reaction of pyruvate with thiamine pyrophosphate, a derivative of vitamin B, The hydrogen on the heterocyclic thiamine pyrophosphate is weakly acidic and can be removed by reaction with base to yield a nucleophilic ylide much like the phosphorus ylides u.sed in Wittig reactions /Section 19.12>. This nucleophilic yJide adds to the ketone carbonyl group of pyruvate to yield a tetrahedral intermediate. 

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. 

Nature uses the two-carbon acetate fragment of acetyd CoA as the major building block for synthesis. Acetyl CoA can act not only as an electrophilic acceptor, being attacked by nucleophiles at the carbonyl group, but also as a nucleophilic donor by loss of its acidic a hydrogen. Once formed, the enolate ion of acetyl CoA can add to another carbonyl group in a condensation reaction. For example, citric acid is biosynthesized by nucleophilic addition of acetyl CoA to the ketone carbonyl group of oxaloacetic acid (2-oxob i-tanedioic acid) in a kind of mixed aldol reaction. 

STEP 1 Nucleophilic addition of thiamine pyrophosphate to the ketone carbonyl group of pyruvate yields an intermediate addition product. 

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