Alkylation propanoates from

The alkoxide pathway occurs by initial insertion of CO into a palladium alkoxide, followed by insertion of the alkene into the bond between the metal and the alkoxycarbonyl group to form a paUadium-alkyl complex (Scheme 17.18). Protonation of this metal alkyl by alcohol would form the free organic product and regenerate the paUadium alkoxide. This mechanism has now been ruled out for the reactions of ethylene to form methyl propanoate. Although each of these steps has precedent, the absence of reduction products from the alkoxide argues against this pathway. Moreover, the alkyl generated from insertion of ethylene into the palladium-alkoxycarbonyl complex (Scheme 17.18) is chelated to the metal, and metha-nolysis of this species is slower than the steps of the alternative hydride mechanism. ... 

Kolbe noted also the formation of traces of methyl acetate and butyl valerate from electrolysis of acetate and valerate respectively. Careful analysis of reaction products by Petersen (1900) identified compounds which are today formulated as being derived from carbocations formed by loss of one electron from the alkyl radical [50]. Propanoic acid gives mostly ethene while butanoic acid and 2-methyl-propanoic acid give mostly propene. Acetate and long chain alkylcarboxylates give mostly the Kolbe type dimer hydrocarbon on electrolysis of their potassium salts in concentrated solution at a platinum electrode, using high current density and low temperatures [51]. 

Menthyl isocyanopropanoate (5) has been alkylated by means of sodium hydride in tetrahydrofuran and subsequent addition of 3,4-dimethoxybenzyl bromide to give the product 6 in high yield115. The latter was transformed into a-methyl-(3,4-dimethoxy)benzylalanine hydrochloride (7, 85% overall yield from the propanoate) [a] 0 —0.8° (c = 7.5, CH3OH) mp 162-165 °C (decomp). The optically pure form has [a]p7 —8.8° (c = 0.84, CH3OH) and mp 169-171 °C (decomp). 

Enolate dianions from 3-benzoyl-2-fc-rt-butylT-methyl-5-oxo-4-imidazolidineacetic and -propanoic acids 4, obtained from aspartic and glutamic acid, have also been used in diastcreose-lective alkylation reactions (see Table 4)7. 

The names of esters consist of two words that reflect their formation from an alcohol and a carboxylic acid. According to the 1UPAC rule. Ihe alkyl or aryl group of the alcohol is cited first followed by the carboxylate group of the acid with the ending -ate replacing the -ic of the acid. For example. CHiCHiCOOCH, the methyl ester of propanoic acid, is called methyl propanoate (or methyl propionate, if the trivial name, propionic acid, is used for the carboxylic acid). 

Simple alkylation of the chiral chelate complex leads to formation of chiral dialkylacetic acids (Scheme 109).3S5 388 Simpler chiral enamines can also be used. The formation of chiral propanoic acids results from a resolution of racemic alkyl halides by the interaction of a chiral lithiooxazoline, which recognizes and reacts with one enantiomer at the expense of the other (Scheme 110).389 The above aspects of the asymmetric carbon—carbon bond formation from chiral oxazolines have been reviewed by Meyers.390... 

Henke et al78 reported the resolution of 2(4-isobutylphenyl)propanoic acid 59 (ibuprofen) by transesterification of its corresponding vinylester 61 using lipase from Candida antarctica. Depending on the nucleophile, the vinylester 61 was recovered with 8-99% ee while the alkyl ester 62 or the free acid 59 is recovered with 16-75 % ee. 

Figure 10.10 The synthesis of 2R-methylbutanoic acid, illustrating the use of a chiral auxiliary. The chiral auxiliary is 2S-hydroxymethyltetrahydropyrrole, which is readily prepared from the naturally occurring amino acid proline. The chiral auxiliary is reacted with propanoic acid anhydride to form the corresponding amide. Treatment of the amide with lithium diisopropyla-mide (LDA) forms the corresponding enolate (I). The reaction almost exclusively forms the Z-isomer of the enolate, in which the OLi units are well separated and possibly have the configuration shown. The approach of the ethyl iodide is sterically hindered from the top (by the OLi units or Hs) and so alkylation from the lower side of the molecule is preferred. Electrophilic addition to the appropriate enolate is a widely used method for producing the enantiomers of a-alkyl substituted carboxylic acids...

Let s try a synthesis. Suppose the target is ethyl 2-methyl-3-oxo-2-propylpentanoate. The presence of the /3-ketoester functionality suggests employing an alkylation reaction and/or an ester condensation. In one potential pathway, the propyl group can be attached by alkylation of a simpler /3-ketoester. Further retrosynthetic analysis suggests that the new target (ethyl 2-methyl-3-oxopentanoate) can be prepared from ethyl propanoate by a Claisen ester condensation. 

In the aliphatic series there has been little work performed with fluoroalkylamine reagents (FAR). They do not seem to work well, since, for example, methyl 2-hydroxy-2-melhyl-propanoate and the Yarovenko reagent, 2-chloro-/V,/V-diethyl-l,1.2-trinuoroethylamine (1), give the desired methyl 2-fluoro-2-mclhylpropanoate in only 10% yield elimination is the main reaction. Good yields of fluorinated products are obtained from 2-aryl-2-hydroxy-acetates, where elimination cannot occur (sec Table 9). When alkyl substituents arc present in the a-position, elimination products arc again found. 

Enolates derived from 2-phenylselanyl esters react with various electrophiles such as alkyl halides and benzeneselenenyl halides [45]. The Michael addition of the enolate, formed from ferf-butyl 2-phenylselanyl propanoate, to (R)-5-n-octyl(5ff)furan-2-one and subsequent iodination afforded a key intermediate for the total synthesis of (-)-Avenaciolide [46] (Scheme 37). 

The alkylation of the enolate derived from ethyl 2-fluoro-2-phenylselanyl propanoate, followed by an oxidative deselenenylation, allowed the stereoselective synthesis of ( )-a-fluoro-a, -unsaturated esters [47] (Scheme 38). 

Anhydrous hydrogen fluoride is much more effective and cleaves all three groups at room temperature in an autoclave. Alternatively, trialkylboranes are readily protonolyzed by carboxylic acids. Two alkyl groups are removed from many trialkylboranes by treatment with excess of an anhydrous carboxylic acid at room temperature, and the third is removed on heating. Typically, the trialkylborane is refluxed for 2-3 h with propanoic acid in diglyme to effect complete conversion (equation 55). The method is considered in greater detail in Section 3.10.7.2. Alternatively, 2,2-dimethylpropanoic acid can be used to catalyze the reaction with water or other protic species. 2 76... 

Alcohols and phenols are quite different from the hydrocarbons and alkyl halides we ve studied thus far. Not only is their chemistry much richer, their physical properties are different as well. Figure 17.1, which provide a comparison of the boiling points of some simple alcohols, alkanes, and chloroalkanes, shows that alcohols have much higher boiling points. For example, 1-propanol (MW = 60), butane (MW = 58), and chloroethane (MW = 65) have similar molecular weights, yet 1-propano) boils at 9TC, -0.5 C Ibr the alkane and 12.5°C for the chloroalkane. 

The enamines originating from Dieckmann-Ziegler cyclizations of ethyl 3-[alkyl(4-cyanopyri-dazin-3-yl)amino]propanoates on acidic hydrolysis give the corresponding enols, which are air sensitive and therefore are obtained as a mixture with their oxidation products20 (see Section 7.2.1.1.1.3.). 

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