Ketenes Ketones

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

The alkylphenylacetyi chloride 843 and benzoyl chloride undergo decarbo-nylative cross-condensation to give the enone 845 in the presence of EtiNf723]. The reaction is e.xplained by the insertion of the ketene 844 into the Pd-aryl bond and, 3-elimination. To support this mechanism, o, d-unsaturuted ketones are obtained by the reaction of ketenes with aroyl chlorides[724]. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Ketone Synthesis. In the Friedel-Crafts ketone synthesis, an acyl group is iatroduced iato the aromatic nucleus by an acylating agent such as an acyl haUde, acid anhydride, ester, or the acid itself. Ketenes, amides, and nittiles also may be used aluminum chloride and boron ttitiuotide are the most common catalysts (see Ketones). 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Ketones with labile hydrogen atoms undergo enol acetylation on reaction with ketene. Strong acid catalysis is required. If acetone is used, isoptopenyl acetate [108-22-5] (10) is formed (82—85). Isopropenyl acetate is the starting material for the production of 2,4-pentanedione (acetylacetone) [123-54-6] (11). 

Ketene can also be added to trihalosubstituted aldehydes or ketones (12) to form 4-trihalomethyloxetanones. If this addition is performed in the presence of optically active bases such as quinine [130-95-0] chiral lactones are obtained (41,42). 

Thermal Stability. The saturated C —C 2 ketones are thermally stable up to pyrolysis temperatures (500—700°C). At these high temperatures, decomposition can be controlled to produce useful ketene derivatives. Ketene itself is produced commercially by pyrolysis of acetone at temperatures just below 550°C (see Ketenes, ketene dil rs, and related substances). 

O-Acylation of 2-nitropropane occurs on reaction with either ketene or acetic anhydride (61) in the presence of dry sodium acetate at 70—80°C. Ketovinylation of 2-nitropropane at the 1-position occurs on treatment of sodium 2-propanenitronate with a chlorovinyl ketone (62). 

Carbonyl Compounds. Cychc ketals and acetals (dioxolanes) are produced from reaction of propylene oxide with ketones and aldehydes, respectively. Suitable catalysts iaclude stannic chloride, quaternary ammonium salts, glycol sulphites, and molybdenum acetyl acetonate or naphthenate (89—91). Lactones come from Ph4Sbl-cataly2ed reaction with ketenes (92). 

The reaction of ketene itself with tettaalkyl titanates followed by a ketone R R C=0 gives P-hydroxy-esters, R R C0HCH2C02R. Polyinsertion of ketene and aldehyde into the Ti—O bond leads to di-, tri-, and tetraesters, eg, H0CR R CH2C02CR R CH2C02R (200). 

The aromatic primary and secondary stibines are readily oxidized by air, but they are considerably more stable than their aHphatic counterparts. Diphenylstibine is a powerful reducing agent, reacting with many acids to Hberate hydrogen (79). It has also been used for the selective reduction of aldehydes and ketones to the corresponding alcohols (80). At low temperatures, diphenylstibine undergoes an addition reaction with ketene (81) ... 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

More definitive evidence for the formation of an oxirene intermediate or transition state was presented recently by Cormier 80TL2021), in an extension of his earlier work on diazo ketones 77TL2231). This approach was based on the realization that, in principle, the oxirene (87) could be generated from the diazo ketones (88) or (89) via the oxocarbenes 90 or 91) or from the alkyne (92 Scheme 91). If the carbenes (90) (from 88) and (91) (from 89) equilibrate through the oxirene (87), and if (87) is also the initial product of epoxidation of (92), then essentially the same mixture of products (hexenones and ketene-derived products) should be formed on decomposition of the diazo ketones and on oxidation of the alkyne this was the case. 

The first /3 -lactam was produced by addition of a ketene to an imine and there are now many examples of this type of approach. The ketenes are most frequently generated in situ from acid chlorides by dehydrohalogenation, but have also been produced from diazo ketones, by heating of alkoxyacetylenes and in the case of certain cyanoketenes by thermolysis of the cyclic precursors (162) and (163). 

The most efficient intramolecular secondary processes competing with the acyl-alkyl diradical recombination in five-membered and larger cyclic ketones are hydrogen shifts resulting in the disproportionation of the diradical to either ketenes or unsaturated aldehydes [cf. (5) (4) (6)]. 

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