Rearrangements carbon chain branching

From a retrosynthetic point of view, the Meerwein-Eschenmoser-Claisen rearrangement shares the basic Claisen retron, a y,<5-unsaturated carbonyl compound, with other variants of the reaction. More specifically, its retron consists of a two-carbon chain branching off an allyhc stereocenter and terminating in an amide or a functional group derived thereof Such a motif can be readily identified in numerous natural products and other synthetic targets. 

The regioselectivity of this latter reaction pathway may be diminished owing to the tendency of carbocations to rearrange, particularly when branching of the carbon chain occurs in the -position. Hence the method is preparatively useful only with secondary alcohols (e.g. butan-2-ol) where one unique secondary carbocation is involved (see also Section 5.5.2, p. 560). 

Rearrangement of the carbon chain occurs easily when halogen (X) is substituted for OH in much-branched primary alcohols or secondary alcohols having a tertiary H atom in the -position tertiary halides are formed preferentially, e.g., ter t-pentyl bromide is the main product from neopentyl alcohol ... 

The synthetic design based on the molybdic acid catalyzed carbon-skeleton rearrangement of the branched chain aldose as applied above to prepare sedo-heptulose has also been exploited for the synthesis of D-glycero-D-ido-octu ose [63]. The necessary branched-chain aldose 45,2-C-(hydroxymethyl)-D-g/ycero-D-gw/o-heptose,was obtained by the potassium carbonate catalyzed aldolization of the D-glycero-D-gulo-heiptose derivative 43 [64], which has an anchored configuration at C-2,by 2,3-0-isopropylidenation with formaldehyde and by subsequent deprotection of the aldolization product 44. 

Homologation of a broad range of aliphatic acid structures and carbon numbers, with extensive rearrangement during the homologation of certain branched-chain acids. 

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

Aliphatic Acids The molecular ion peak of a straight-chain monocarboxylic acid is weak but usually discernible. The most characteristic (sometimes the base) peak is m/z 60 resulting from the McLafferty rearrangement. Branching at the a carbon enhances this cleavage. 

Branched carbon skeletons are formed by standard reaction types but sometimes with addition of rearrangement steps. Compare the biosynthetic routes to three different branched five-carbon units (Fig. 17-19) The first is the use of a propionyl group to initiate formation of a branched-chain fatty acid. Propionyl-CoA is carboxylated to methylmalonyl-CoA, whose acyl group is transferred to the acyl carrier protein before condensation. Decarboxylation and reduction yields an acyl-CoA derivative with a methyl group in the 3-position. 

The third type of carbon-branched unit is 2-oxoisovalerate, from which valine is formed by transamination. The starting units are two molecules of pyruvate which combine in a thiamin diphosphate-dependent a condensation with decarboxylation. The resulting a-acetolactate contains a branched chain but is quite unsuitable for formation of an a amino acid. A rearrangement moves the methyl group to the (3 position (Fig. 24-17), and elimination of water from the diol forms the enol of the desired a-oxo acid (Fig. 17-19). The precursor of isoleucine is formed in an analogous way by condensation, with decarboxylation of one molecule of pyruvate with one of 2-oxobutyrate. 

All aspects of the structure, reactivity and chemistry of fluorine-containing, carbon-based free radicals in solution are presented. The influence of fluorine substituents on the structure, the stability and the electronegativity of free radicals is discussed. The methods of generation of fluorinated radicals are summarized. A critical analysis of the reactivities of perfluoro-n-alkyl, branched chain perfluoroalkyl and partially-fluorinated free radicals towards alkene addition, H-atom abstraction, and towards intramolecular rearrangement reactions is presented. Lastly, a summary of the synthetically-useful chemistry of fluorinated radicals is presented. 

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