Three-carbon condensation

Preparative importance attaches further to Hellmann and Dietrich s so-called asymmetric three-carbon condensation, in which, within certain limitations, two different compounds containing active methylene groups are linked together by formaldehyde with formation of two new carbon-carbon bonds. For example, dibenzoylmethane, dimethyl (acetylamino)malonate, and formaldehyde afford an 88% yield of dimethyl oc-(acetylamino)-oc-(2,2-di-benzoylethyl)malonate [ 1 -(acetylamino-3-benzoyl-4-oxo-4-phenyl-1,1 -butane-dicarboxylate].6 7 2... 

The Mannich condensation has traditionally been carried out in the presence of water as a three-component condensation involving a carbonyl compound (or related carbon nucleophile), formaldehyde, and a primary or secondary amine. The initial step is a condensation between the latter two reactants to form a mono- or dialkyl(methylene)ammonium ion which subsequently serves as the electrophilic partner in the reaction. With unsymmetrical ketones aminomethylation generally occurs at both positions to give mixtures of isomeric 3-amino ketones. The ratio of the isomers depends strongly on the structure of the ketone, and the more highly branched (3-amino ketone usually predominates. 

When the organism was exposed to a high concentration of [2-acetate for a brief period, certain rows of carbons (mostly three carbons in a row) in brevetoxin B had C-C spin-spin couplings (JO) (Scheme 7A). These couplings clearly indicate rather "fresh" condensations between actate methyl-derived carbons. Similar spin-spin couplings were not observed when [l- C]acetate was fed under the same condition. 

At low temperatures cyclopropenones and enamines or ketene acetals were shown to yield 2-azonia-bicyclo(3,l, 0)hex-3-enolates-3 (371, X=0), which can be isomerized thermally to penta-2,4-diene amides(372, X=0). At elevated temperatures the amides were found to be the principal products arising from C-N-insertion 237) (insertion of the cyclopropenone three-carbon unit into the C-N bond of the enamine). These were accompanied in some cases by 3-aminoenones 373 arising from C-C-insertion 237) (insertion of the cyclopropenone into the C-C double bond of the enamine) and a-amino cyclopentenones 375 formed by Stevens rearrangement of the ylide 369 and cyclopentenones 374 ( condensation 237)). 

Flavan-3-ols orflavanols have a saturated three-carbon chain with a hydroxyl group in the C3 position. In foods they are present as monomers or as proanthocyanidins, which are polymeric flavanols (4 to 11 units) known also as condensed tannins. In foods they are never glycosylated. 

Flavonoids are the largest class of phenylpropanoids in plants. The basic flavonoid structure is two aromatic rings (one from phenylalanine and the other from the condensation of three malonic acids) linked by three carbons (Fig. 3.6). Chalcone is converted to naringenin by the enzyme chalcone isomerase, which is a key enzyme in flavonoid synthesis. This enzyme, like PAL and chalcone synthase (CHS), is under precise control and is inducible by both internal and external signals. Naringenin is the... 

Arylbenzoxazoles were prepared by Pd-catalyzed three-component condensation of aryl halides with o-aminophenols and carbon monoxide followed by dehydrative cyclization [24], A variant of such methodology using o-fluorophenylamines in place of o-aminophenols was used to synthesize arylbenzoxazoles [25]. 

Electron-spin resonance (e.s.r.) spectra with characteristic hyperfine structure have been recorded during the initial stages of the Maillard reaction between various sugar and amino compounds. The products responsible for the spectra appear to be IV, Af -disubstituted pyrazine radical cations. The pyrazine derivatives are assumed to be formed by the bimolecular condensation of two- and three-carbon enaminol compo-... 

The aromatic 7r-electron system of thienothiophenes and related compounds containing two condensed rings comprises electrons from three carbon-carbon double bonds and unshared electron pairs from two heteroatoms, and thus is similar to that of naphthalene. 

The azomethine ylides applied in synthesis can be divided into two groups. The traditional azomethine ylide 2 is one that consists of a central nitrogen atom with three carbon substituents (Scheme 12.5). This type of azomethine ylide is most frequently formed by the condensation of an aldehyde with a secondary amine 1. The second type are the so-called stabilized azomethine ylides 4. They consist of a central nitrogen atom with two carbon substituents and the nitrogen atom also... 

The acid portion of 1 was assembled by enantio-and diastereocontrolled addition of Z-crotyl borane to the aldehyde 8, following the Brown protocol. Hydroboration and oxidation led to 9, which was condensed with the allenyl silane 10 to give 11 with high diastereocontrol. Conversion of the alcohol to the iodide followed by three-carbon homologation by the Myers procedure then led to 1, which was cyclized with > 10 1 regio- and diasterocontrol to give 12. Ozonolysis and methylenation of the less hindered ketone then delivered 3. 

A three-carbon unit can be introduced on ketosugars under Reformatsky conditions, as recently demonstrated by several groups [33,34], The analogous Dreiding-Schmidt procedure has also been applied in this case with successful double stereodifferentiation [35]. This is exemplified on ketone 18 which yields lactone 20 as a single isomer (see Scheme 10). The condensation on ketosugars of trimethylsilylacetate [36] or acrylate [33], in the presence of fluoride ion, has also been used with success for the synthesis of P-hydroxy acids or ra-methylene-y-lactones, respectively. 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

The six carbons of the benzene ring of the aromatic amino acids are derived from the four carbons of erythrose 4-phosphate and two of the three carbons of phosphoenolpyruvate (PEP). The initial step in the pathway (Fig. 25-1, step a) is the condensation of erythrose 4-P with PEP and is catalyzed by 3-deoxy-D-arafrmo-heptulosonate-7-phosphate (DAHP) synthase. Closely analogous to an aldol condensation, the mechanism provides a surprise.10 When PEP containing lsO in the oxygen bridge to the phospho group reacts, the lsO is retained in the eliminated phosphate biochemical intuition would suggest that it should stay in the... 

Dehydration of 3-dehydroquinate (step c), the first step in Eq. 25-3, is the first of three elimination reactions needed to generate the benzene ring of the end products. This dehydration is facilitated by the presence of the carbonyl group. After reduction of the product to shikimate (step d)19 a phosphorylation reaction (step e)20,21 sets the stage for the future elimination of Pj. In step/, condensation with PEP adds three carbon atoms that will become the a, P, and... 

---