Esters from cyclic ketones

Figure 3.62 Iron (II) activation of hydrogen peroxide to produce ring-opened methyl esters from cyclic ketones.

Hydroxycarboxylic acid esters from cyclic ketones... 

The Baeyer—Villiger oxidation is also widely used for synthesizing lactones (cyclic esters) from cyclic ketones. A common reagent used to carry out the Baeyer—Villiger oxidation is wt fer-chloroperoxybenzoic acid (wCPB A). Certain other peroxycarboxylic acids can be used as well. The following is a mechanism for Baeyer—Villiger oxidation. 

Nitrosyl chloride Nitrosolysis of ketones co-Oximinocarhoxylic acid esters from cyclic ketones... 

Ketocarboxylic acid esters from cyclic ketones s. 17, 194 Nitric acid... 

The enamines derived from cyclic ketones give the normal alkylated products, although there is some evidence that unstable cycloadducts are initially formed (55b). Thus the enamine (28) derived from cyclohexanone and pyrrolidine on reaction with acrylonitrile, acrylate esters, or phenyl vinyl sulfone gave the 2-alkylated cyclohexanones (63) on hydrolysis of the intermediates (31,32,55,56). These additions are sensitive to the polarity of the solvent. Thus (28) in benzene or dioxane gave an 80% yield of the... 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

Homer-Wadsworth-Emmons reactions of ketones and aldehydes with phosphono-acetate esters, (R20)2P(=0)CH2C02R1, produce E/Z mixtures of a, /Tunsaturated esters. Use of the conventional reagent, sodium hydride, gives some selectivity. The combination of tin(II) triflate and A -cthylpipcndine enhances—and sometimes also reverses—the selectivity in most cases studied.71 Six-membered oxo-coordinated tin intermediates are proposed to control the selectivities observed. A similarly selective synthesis of trisubstituted exocyclic alkenes from cyclic ketones has been reported.72... 

Keto esters react with arylenediamines when heated in neutral solvents to give benz-imidazolinones in a reaction which is capable of extension to the jS-keto esters derived from cyclic ketones. Under acidic conditions, o-phenylenediamine gives a 78% yield of... 

The Baeyer-Wlliger oxidation of ketones affords esters (from open-chain ketones) and lactones (from cyclic ketones), respectively. It is typically carried out using nucleophilic oxidants, such as peracids or dihydrogen peroxide in the presence of bases (29). Nucleophilic oxidants are required because the first step of the reaction mechanism is the addition of the peroxidic oxidant to the ketone s carbonyl function, affording the so-called Criegee-intermediate (Scheme 10). The subsequent cleavage of the 0 0 bond in the latter, and the concerted shift of yield the ester (lactone) product. In enzymatic Baeyer-Vlliger oxidations, flavin hydroperoxides such as 26 act as the nucleophilic oxidant (30). 

Esters can also be formed upon oxidation of ketones with a peroxyacid oxidizing agent (such as mCPBA or CF3CO3H). This Baeyer-Villiger oxidation is especially useful in the preparation of cyclic esters (called lactones) from cyclic ketones. 

The lithiated oxathiolan dioxide (19) has been used as a carbonyl anion equivalent to give high yields of aldehydes from alkyl halides and acyloins from cyclic ketones.The /8-acyl anion equivalent (20 X = Li), which can be prepared from the stannylated diene (20 X = SnRs) by metal exchange, reacts with a variety of electrophiles (E ) to give dienes (20 X = E) in good to excellent yields.The thiophosphate (21) gives a,/3-unsaturated esters in 48—68% yield... 

A two-carbon ring expansion of cyclic ketones was achieved by the addition of acetylenic esters and diesters to the enamine derivatives of the ketones, and reported almost simultaneously from several laboratories (337-343). The intermediate bicyclic adduct could be isolated in some cases. 

The reaction described is of general synthetic utility for the preparation of a variety of cyclic /3-keto esters from the corresponding ketones. Using this procedure the 2-carbethoxy-cycloalkanones have been prepared from cyclononanone, cyclo-decanone, and cyclododecanone in yields of 85%, 95%, and 90%, respectively. The procedure is simpler and gives much higher yields than other synthetic routes to these systems. 

The molecular ion can be very small or nonexistent. Esters where R is greater than methyl form a protonated acid that aids in the interpretation (e.g., m/z 47, formates m/z 61, acetates m/z 75. propionates m/z 89, butyrates etc.). Interpreting the mass spectra of ethyl esters may be confusing without accurate mass measurement because the loss of C2H4 can be confused with the loss of CO from a cyclic ketone. 

Bisulfite addition products are formed from aldehydes, methyl ketones, cyclic ketones (generally seven-membered and smaller rings), a-keto esters, and isocyanates, upon treatment with sodium bisulfite. Most other ketones do not undergo the reaction, probably for steric reasons. The reaction is reversible (by treatment of the addition product with either acid or base ) and is useful for the purification of the starting compounds, since the addition products are soluble in water and many of the impurities are not. ... 

Hydride-promoted reactions are also well known, such as the acrylic and vinylacrylic syntheses (examples 7-10, Table VII). Some less-known compounds, which form in the presence of halide ions added to tetracar-bonylnickel, have been described by Foa and Cassar (example 11, Table VII). Reaction of allene to form methacrylates, and of propargyl chloride to give itaconic acid (via butadienoic acid), have been reported (examples 13 and 14, Table VII). 1,5-Hexadiene has been shown to be a very good substrate to obtain cyclic ketones in the presence of hydrogen chloride and tetracarbonylnickel (example 15, Table VII). The latter has also been used to form esters from olefins (example 16, Table VII). In the presence of an organic acid branched esters form regioselectivity (193). 

Alkyl-3-cyano-4-hydroxythiophenes 625 were obtained from the reaction of 2,3-allenenitriles 610 with mercaptoacetates 622. The presence of the ester group leads to the formation of cyclic ketones 623, which undergo migration of the C=C and C=0 bonds to form thiophenes 625 [276]. 

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