Carboxylic acids reaction with allylic halides

Michael addition reactions, 4, 302 reactions with allyl halides, 4, 301 Pyrrole-2-carboxylic acid, 1-methyl-conformation, 4, 194 esters... 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

Seebach and Naef1961 generated chiral enolates with asymmetric induction from a-heterosubstituted carboxylic acids. Reactions of these enolates with alkyl halides were found to be highly diastereoselective. Thus, the overall enantioselective a-alkyla-tion of chiral, non-racemic a-heterosubstituted carboxylic acids was realized. No external chiral auxiliary was necessary in order to produce the a-alkylated target molecules. Thus, (S)-proline was refluxed in a pentane solution of pivalaldehyde in the presence of an acid catalyst, with azeotropic removal of water. (197) was isolated as a single diastereomer by distillation. The enolate generated from (197) was allylated and produced (198) with ad.s. value >98 %. The substitution (197) ->(198) probably takes place with retention of configuration 196>. 

IV. Reactions of Metalated Carboxylic Acids - Metalated carboxylic acids react with most electrophiles It the dianlon is associated with alkali metal cations. However, Cu(i) dianions22 react readily only with activated allylic or benzylic halides. 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

The lithium tetraalkylalanates obtained in situ firom these reactions are easily involved in the subsequent transformations. Cross-coupling of lithium tetraalkylalanates with allyl halides in the presence of copper compounds (CuBr, Cul, CuCN, CuCl, Cu(OAc)2) furnishes olefins that differ firom the initial ones by three carbon atoms [23], and CuCl-catalyzed reaction with propargyl bromide produces terminal allenes in high yields [24]. Such cross-couplings were also performed with allene bromide [25], carboxylic acid halides [26], acrolein [27], and methyl vinyl ketone... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

Carboxylic acids can be alkylated in the a position by conversion of their salts to dianions [which actually have the enolate structures RCH=C(0")2 ] by treatment with a strong base such as LDA. The use of Li as the counterion is important, because it increases the solubility of the dianionic salt. The reaction has been applied to primary alkyl, allylic, and benzylic halides, and to carboxylic acids of the form RCH2COOH and RR"CHCOOH. This method, which is an example of the alkylation of a dianion at its more nucleophilic position (see p. 458),... 

Deprotonation of O-alkyl carbamates may be achieved in an enantioselective manner with s-BuLi-(-)-sparteine, and the most effective of these reactions employ the oxazolidinones 411. The related compounds 412 perform similarly, but have less neat NMR spectra. Enantioselective lithiation of 413, followed by carboxylation and methylation with diazomethane, generates the protected a-hydroxy acid 414 in >95% ee.176 Many other electrophiles perform well in the quench step, but not allylic or benzylic halides, which lead to partial racemisation.177 30... 

The mechanisms of two other reactions described in Sect. 2.2 involve slow proton transfer to unsaturated carbon. The general acid catalysed cleavage of vinyl mercuric halides [42, 50] for example, allyl mercuric iodide, CH2=CHCH2HgI (XXII), gives Bronsted exponents around 0.7. Linear Bronsted plots are obtained with carboxylic acid catalysts but, as observed in other A—SE 2 reactions, general acids of different structural types (for example, hydronium ion or bisulphate ion) show substantial deviations. Bronsted catalysis of the hydrolysis of diazo compounds (N2 =CR X) has been studied by the groups of Albery and Kreevoy. With... 

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