Unsaturated acids, alkylation

Amides in general are stable to elevated processing temperatures, ak oxidation, and dilute acids and bases. StabiUty is reduced in amides containing unsaturated alkyl chains unsaturation offers reactive sites for many reactions. 

Addition of water (36) or alcohols (37—39) direcdy to butadiene at 40—100°C produces the corresponding unsaturated alcohols or ethers. Acidic ion exchangers have been used to catalyze these reactions. The yields for these latter reactions are generally very low because of unfavorable thermodynamics. At 50°C addition of acetic acid to butadiene produces the expected butenyl acetate with 60—100% selectivity at butadiene conversions of 50%. The catalysts are ion-exchange resins modified with quaternary ammonium, quaternary phosphonium, and ammonium substituted ferrocenyl ions (40). Addition of amines yields unsaturated alkyl amines. The reaction can be catalyzed by homogeneous catalysts such as Rh[P(C(5H5)3]3Q (41) or heterogeneous catalysts such as MgO and other solid bases (42). 

The technique for the introduction of lipidic groups into compounds that is favored by the authors is the use of lipoamino acids (Laas) (Fig, 1). These are a-amino acids with alkyl sidechains that can be varied in length, substitution, and degree of unsaturation simply by altering the bromoalkane used in the synthesis (6). The benefits of Laas include the ability to couple them using standard peptide coupling procedures, making them ideal for use in solid phase syntheses. Their bifunctional nature means they can be introduced into a peptide at any point in the sequence and the number of Laas introduced is easily varied. 

The Potassium complex of I8-Crown-6 or Potassium Naph-thalenide effects ring-opening to give acetates or their alkylated derivatives in good yield (eq 3). Treatment of the reaction mixture obtained from p-methyl-p-propiolactone and potassium-18-crown-6 with hydrochloric acid or alkyl halides gives the acetate (S) or its alkylated derivative (6), respectively. The a,3-unsaturated carboxylic acid (7) or its ester (8) is formed by the action of the potassium naphthalenide-18-crown-6 complex. ... 

Fatty acids in biological systems usually contain an even number of carbon atoms, typically between 14 and 24 (Table 12.1). The 16- and 18-carbon fatty acids are most common. The hydrocarbon chain is almost invariably unbranched in animal fatty acids. The alkyl chain may be saturated or it may contain one or more double bonds. The configuration of the double bonds in most unsaturated fatty acids is cis. The double bonds in polyunsaturated fatty acids are separated by at least one methylene group. 

The total unsaturation from Equation (7) can be apportioned into contributions from alicyclic structural moieties such as furanose and pyra-nose rings, aromatic structural moieties such as benzene rings, and carbonyl-containing moieties such as carboxylic acids, esters, amides, aldehydes, and ketones. Olefinic moieties such as the unsaturated alkyl chains of some lipids are thought to be of only minor importance. Equation (7) can thus be rewritten as... 

The carbonium ion abstracts a tertiary hydrogen from the isoparaffin, yielding a hexyl ion which then abstracts a hydride ion from the unrearranged isoparaffin, saturates itself, and starts a new cycle. Carbonium ions are formed when unsaturated compounds are dissolved in proton acids or, in general, if the compound is sufficiently basic relative to the acid, i.e., alcohols, ethers, esters, acid anhydrides, alkyl-substituted aromatic compounds will form carbonium ions in sulfuric, hydrofluoric, and other acid solvents. 

Mixed bimetallic reagents possess two carbon-metal bonds of different reactivity, and a selective and sequential reaction with two different electrophiles should be possible. Thus, the treatment of the l,l-bimetailic compound 15 with iodine, at — 78"C, affords an intermediate zinc carbenoid 16 that, after hydrolysis, furnishes an unsaturated alkyl iodide in 61% yield [Eq. (15) 8]. The reverse addition sequence [AcOH (1 equiv), —80 to — 40 C iodine (1 equiv)] leads to the desired product, with equally high yield [8]. A range of electrophile couples can be added, and the stannylation of 15 is an especially efficient process [Eq. (16) 8]. A smooth oxidation of the bimetallic functionality by using methyl disulfide, followed by an acidic hydrolysis, produces the aldehyde 17 (53%), whereas the treatment with methyl disulfide, followed by the addition of allyl bromide, furnishes a dienic thioether in 76% yield [Eq. (17) 8]. The addition of allylzinc bromide to 1-octenyllithium produces the lithium-zinc bimetallic reagent 18, which can be treated with an excess of methyl iodide, leading to only the monomethylated product 19. The carbon zinc bond is unreactive toward methyl iodide and, after hydrolysis, the alkene 19... 

Alkylative esterification of carboxylic acids with alkyl halides are effected by action with TMG (1) [65]. An ester is given by the TMG (1) mediated reaction of y-hydroxy-a,p-unsaturated carboxylic acid with methyl iodide without lactone formation after isomerization [65a]. Barton s base effectively works in the alkylation of sterically hindered carboxylic acid [3]. Ethanolysis of the acetate of tertiary alcohol occurred easily in 86% yield in the presence of BTMG (2) [66] (Scheme 4.24). 

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