Carboxylic acids from alkynes

Three highly useful synthetic transformations are presented in this section the synthesis of isoflavones from chalcones, the synthesis of a-arylalkanones from arylalkenes, and the synthesis of a-arylalkanoic acids from aryl ketones. Two others are potentially useful methods, but are not as yet widely used the preparation of a-branched carboxylic acids from alkynes, and the ring expansion and ring contraction of cyclic alkenes and ketones. 

Using stoichiometric amounts of an alkylzinc reagent and catalytic amounts of Ni(0)/DBU, Mori was able to prepare a number of p-aUcylated or arylated a,-P-unsaturated carboxylic acids from alkynes and CO2 (Scheme 5.12) [56, 57]. Through a frans-metalation reaction with the oxanickelacyclopentenone intermediate, the alkyl zinc reagent effected the reductive elimination of the product from the nickel center with concomitant regeneration of the active zerovalent catalyst. 

Alkynes, like alkenes, can be cleaved by reaction with powerful oxidizing agents such as ozone or KMnC, although the reaction is of little value and we mention it only for completeness. A triple bond is generally less reactive than a double bond and yields of cleavage products are sometimes low. The products obtained from cleavage of an internal alkyne are carboxylic acids from a terminal alkyne, CO2 is formed as one product. 

Examples of alkylation, dealkylation, homologation, isomerization, and transposition are found in Sections 1,17,33, and so on, lying close to a diagonal of the index. These sections correspond to such topics as the preparation of alkynes from alkynes carboxylic acids from carboxylic acids and... 

Alkenes and Alkynes. A series of metal carbonyl cations, such as [Au(CO)n]+,287,288 [c-Pd( i-CO)2]2+,289 [Rh(CO)4]+,290 and [(Pt(CO)3)2]2+,291 was found to induce the formation of carboxylic acids from alkenes and CO in the presence of H2SO4 under mild conditions. A novel water-soluble Pd catalyst292 and Pd complexes of calixarene-based phosphine ligands293 showed high activity in the regioselective carboxylation of vinyl arenes to yield 2-arylpropionic acids or... 

Show how to synthesize carboxylic acids from oxidation of alcohols and aldehydes. Problems 20-36, 39, and 44 carboxylation of Grignard reagents, oxidative cleavage of alkenes and alkynes, hydrolysis of nitriles, and oxidation of alkylbenzenes. 

Hydrocarhoxylation and chlorocarboxylation. Pd/C catalyzes the formation of carboxylic acids from conjugated dienes and alkynes. The reaction system also contains CO, HCOOH (or oxalic acid), PhsP, and l,4-bis(diphenylphosphino)butane. For chlorocarboxylation, anhydrous HCl is used as a coreagent. ... 

The electrophilic activation of terminal alkynes by arene-ruthenium(II) catalysts has provided selective access to enol esters. Enol esters are much more reactive than alkyl esters and have been used in a variety of reactions. In the past decade, Dixneuf and co-workers have developed selective approaches to the Markovnikov and antz-Markovnikov addition of carboxylic acids across alkynes by employing different arene-ruthenium(II) catalysts [48,53,54]. Of special interest is the synthesis of AT-Boc-protected 1-alanine isopropenyl ester 110 from N-Boc-l-alanine 108 and propyne 109 mediated by (Ty -cymene)RuCl2(PPh3) complex 107 (Scheme 30) [53]. Addition of the amino acid 108 to the propyne 109 proceeded exclusively in the Markovnikov sense and without accompanying racemization of the substrate. 

Lautens and Hulcoop developed a Pd-catalyzed annula-tion of 3-aryl substituted pyrroles to yield indoles, following retro-Diels-Alder loss of cyclopentadiene (Scheme 2, equations 1 and 2) [4]. Miura, Satoh, and coworkers found that indoles were formed from Af-methylpyrrole-2 carboxylic acid and alkynes as catalyzed by palladium (equation 3) [5, 6]. The indoles themselves undergo this oxidative coupling with alkynes to form octa-substituted carbazoles, e.g.4[6]. 

J-unsaturated ester is formed from a terminal alkyne by the reaction of alkyl formate and oxalate. The linear a, /J-unsaturated ester 5 is obtained from the terminal alkyne using dppb as a ligand by the reaction of alkyl formate under CO pressure. On the other hand, a branehed ester, t-butyl atropate (6), is obtained exclusively by the carbonylation of phenylacetylene in t-BuOH even by using dppb[10]. Reaction of alkynes and oxalate under CO pressure also gives linear a, /J-unsaturated esters 7 and dialkynes. The use of dppb is essen-tial[l 1]. Carbonylation of 1-octyne in the presence of oxalic acid or formic acid using PhiP-dppb (2 I) and Pd on carbon affords the branched q, /J-unsatu-rated acid 8 as the main product. Formic acid is regarded as a source of H and OH in the carboxylic acids[l2]. 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

How to Use the Book to Locate Examples of the Preparation of Protection of Monofunctional Compounds. Examples of the preparation of one functional group from another are found in the monofunctional index on p. x, which lists the corresponding section and page. Sections that contain examples of the reactions of a functional group are found in the horizontal rows of this index. Section 1 gives examples of the reactions of alkynes that form new alkynes Section 16 gives reactions of alkynes that form carboxylic acids and Section 31 gives reactions of alkynes that form alcohols. 

The degradation of alkynes has been the subject of sporadic interest during many years, and the pathway has been clearly delineated. It is quite distinct from those used for alkanes and alkenes, and is a reflection of the enhanced nucleophilic character of the alkyne C C bond. The initial step is hydration of the triple bond followed by ketonization of the initially formed enol. This reaction operates during the degradation of acetylene itself (de Bont and Peck 1980), acetylene carboxylic acids (Yamada and Jakoby 1959), and more complex alkynes (Figure 7.18) (Van den Tweel and de Bont 1985). It is also appropriate to note that the degradation of acetylene by anaerobic bacteria proceeds by the same pathway (Schink 1985b). 

Arndtsen and coworkers [154] described the first Pd-catalyzed synthesis of miinchnones 6/1-318 from an imine 6/1-316, a carboxylic acid chloride 6/1-317 and CO. The formed 1,3-dipol 6/1-318 can react with an alkyne 6/1-319 present in the reaction mixture to give pyrroles 6/1-321 via 6/1-320, in good yields. The best results in this four-component domino process were obtained with the preformed catalyst 6/1-322 (Scheme 6/1.83). 

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