Alkynes to carboxylic acids

For oxidation of terminal and internal alkynes to carboxylic acids by RuO / Oxone /Na(HC03)/aq. CHjCN-EtOAc (Table 3.4) a mechanism was proposed in which C3H. CCC3H., is oxidised by RuO to the dione via a Ru(Vl) diester (1), with the resulting dione (2) then undergoing Baeyer-Villiger oxidation by HSOj" to give an acid anhydride (3) which was hydrolysed to the acid (Fig. 1.9 R= C3H3) [377]. 

Terminal alkynes are prone to undergo facile oxidative cleavage to yield carboxylic acids with loss of the terminal carbon atom. In fact, most of the oxidizing agents that can be used in the selective oxidation of internal alkenes to 1,2-diketones [Ru04,711 PhIO with Ru catalysts,712 KMn04,713 T1(N03)3,716 0s04718] convert terminal alkynes to carboxylic acids. 

In conjunction with several ruthenium catalysts, C6HsIO oxidizes internal alkynes to a-diketones in 65-85% yield and terminal alkynes to carboxylic acids (70-80% yield).2... 

Although oxidation of l,l-bis(dialkylboryl) compounds with alkaline hydrogen peroxide proceeds with initid hydrolysis rather than oxidation (equation 16), oxidation with excess MCPBA yields carboxylic acids in good yields. The overall process is an excellent route from 1-alkynes to carboxylic acids (equation 39). ... 

Oxone, in conjunction with Ru02, cleaves alkynes to carboxylic acids. 4 Both internal and terminal alkynes are cleaved in short reacton times with high yields (eq 48). Intermediate 1,2-diketones... 

Internal alkynes are oxidized to acytoins by thalliuin(III) in acidic solution (A. McKil-lop, 1973 G.W. Rotermund, 1975) or to 1,2-diketones by permanganate or by in situ generated ruthenium tetroxide (D.G. Lee, 1969, 1973 H. Gopal, 1971). Terminal alkynes undergo oxidative degradation to carboxylic acids with loss of the terminal carbon atom with these oxidants. 

D (and by implication E and F) is para substituted. In addition, both branches must be identical, which means each has one degree of unsaturation (two alkenes and not one alkyne). The branches are -CH=CH2. Hydrogenation converts the branches to -CH2-CH3. Heating with chromic acid eliminates the carbon atom furthest from the ring and converts the remaining carbon atoms to carboxylic acid groups (-CO2H). 

This is one of the most important applications for RuO. Oxidative cleavage of alkenes and alkynes by a variety of reagents has been reviewed [30, 35, 50, 60, 68-71]. The gentler cleavage reactions of alkenes to aldehydes or ketones are considered first (Table 3.3), then the commoner cases of cleavage to carboxylic acids (Table 3.6). 

Oxidative cleavage of alkynes by a variety of reagents has been reviewed [35, 60, 70, 71]. In most cases the CC bond is broken, but in some cases a-diketones are formed instead of, or in addition to, carboxylic acids. Examples of both types of reaction are given in Tables 3.3 and 3.6. 

Ozonolysis of alkynes followed by hydrolysis gives similar products to those obtained from permanganate oxidation. This reaction does not require oxidative or reductive work-up. Unsubstituted carbon atoms are oxidized to CO2, and mono-substituted carbon atoms to carboxylic acids. For example, ozonolysis of 1-butyene followed by hydrolysis gives propionic acid and carbon dioxide. 

The two major characteristic oxidation processes of alkynes are their transformation to 1,2-dicarbonyl compounds and their cleavage reaction to carboxylic acids.710 The structure of the starting compounds has a decisive effect on the selectivity of oxidation. Since 1,2-dicarbonyl compounds proved to be intermediates in further oxidations, carefully controlled reaction conditions are often necessary to achieve selective synthesis. Certain oxidizing agents such as peroxyacids and ozone are nonselective oxidants. 

Alkyne r c=C-r CYP Oxidation to carboxylic acid Aniline —NH2 CYP, NAT, UGT, peroxidase, SULT... 

Halides are second only to carboxylic acids in their versatility in organic synthesis. Functional group transformations into alkenes, alkynes, amines, aldehydes, alcohols, ethers, hydrocarbons, ketones and other groups may be performed with ease in high yield. However, the major synthetic importance of halides arises from the ease by which compounds that contain this functionality may be used in carbon-carbon bond-forming reactions and in the preparation of heterocyclic compounds. 

Alkynes also undergo oxidative cleavage of the a bond and both n bonds of the triple bond. Internal alkynes are oxidized to carboxylic acids (RCOOH), whereas terminal alkynes afford carboxylic acids and CO2 from the sp hybridized C - H bond. 

With internal alkynes two carboxylic acids are formed as products. With terminal alkynes, the sp hybridized C—H bond is converted to CO2. 

Reaction with an amine, AIBN, CO and a tetraalkyltin catalyst also leads to an amide.Benzylic and allylic halides were converted to carboxylic acids electroca-talytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions.Allylic (9-phosphates were converted to allylic amides with CO and ClTi=NTMS, in the presence of a palladium catalyst. Terminal alkynes were converted to the alkynyl ester using CO, PdBr2, CuBr2 in methanol and sodium bicarbonate. ... 

The most important applications of peroxyacetic acid are the epoxi-dation [250, 251, 252, 254, 257, 258] and anti hydroxylation of double bonds [241, 252, the Dakin reaction of aldehydes [259, the Baeyer-Villiger reaction of ketones [148, 254, 258, 260, 261, 262] the oxidation of primary amines to nitroso [iJi] or nitrocompounds [253], of tertiary amines to amine oxides [i58, 263], of sulfides to sulfoxides and sulfones [264, 265], and of iodo compounds to iodoso or iodoxy compounds [266, 267] the degradation of alkynes [268] and diketones [269, 270, 271] to carboxylic acids and the oxidative opening of aromatic rings to aromatic dicarboxylic acids [256, 272, 271, 272,273, 274]. Occasionally, peroxyacetic acid is used for the dehydrogenation [275] and oxidation of aromatic compounds to quinones [249], of alcohols to ketones [276], of aldehyde acetals to carboxylic acids [277], and of lactams to imides [225,255]. The last two reactions are carried out in the presence of manganese salts. The oxidation of alcohols to ketones is catalyzed by chromium trioxide, and the role of peroxyacetic acid is to reoxidize the trivalent chromium [276]. 

The same reagents that oxidize alkenes also oxidize alkynes. Alkynes are oxidized to diketones by a basic solution of KMn04 at room temperature and are cleaved by ozonolysis to carboxylic acids. Ozonolysis requires neither oxidative nor reductive work-up—it is followed only by hydrolysis. Carbon dioxide is obtained from the CH group of a terminal alkyne. 

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