Carbonyl ketone dienes

In the past, this field has been dominated by ruthenium, rhodium and iridium catalysts with extraordinary activities and furthermore superior enantioselectivities however, some investigations were carried out with iron catalysts. Early efforts were reported on the successful use of hydridocarbonyliron complexes HFcm(CO) as reducing reagent for a, P-unsaturated carbonyl compounds, dienes and C=N double bonds, albeit complexes were used in stoichiometric amounts [7]. The first catalytic approach was presented by Marko et al. on the reduction of acetone in the presence of Fe3(CO)12 or Fe(CO)5 [8]. In this reaction, the hydrogen is delivered by water under more drastic reaction conditions (100 bar, 100 °C). Addition of NEt3 as co-catalyst was necessary to obtain reasonable yields. The authors assumed a reaction of Fe(CO)5 with hydroxide ions to yield H Fe(CO)4 with liberation of carbon dioxide since basic conditions are present and exclude the formation of molecular hydrogen via the water gas shift reaction. H Fe(CO)4 is believed to be the active catalyst, which transfers the hydride to the acceptor. The catalyst presented displayed activity in the reduction of several ketones and aldehydes (Scheme 4.1) [9]. 

Analogously to cyclization-carbonylation of dienes, it is possible to carry out synthetically attractive cyclization-carbonylation of a,o>-enones into the bu-tyrolactones 142 (Scheme 63). The reaction can be catalyzed either by the ti-tanocenes 113 or 119. Interestingly, the catalytic cyclization proceeded well only with allylaryl ketones (Table 29). In the case of alkyl ketones or aldehydes only the stoichiometric cyclization was successful [77]. 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

The results of the reductions of some steroidal a,)3-unsaturated ketones have been summarized by Brown. " The carbonyl group is usually reduced to the hydrocarbon, but the behavior of the double bond depends on the structure of the compound undergoing the reduction. Cholest-4-en-3-one gives chol-est-4-ene. Addition of aluminum chloride to a solution of a 4-ene-3,6-dione followed by treatment with LiAIH4 gives the 4-ene-6-one. Steroid 4,6-dien-3-ones yield mixtures of dienes. When the ketone and double bond are in different rings the results become even more complex dienes as well as mono-enes are obtained. 

Thioketals are readily formed by acid-catalyzed reaction with ethane-dithiol. Selective thioketal formation is achieved at C-3 in the presence of a 6-ketone by carrying out the boron trifluoride catalyzed reaction in diluted medium. Selective protection of the 3-carbonyl group as a thioketal has been effected in high yield with A" -3,17-diketones, A" -3,20-diketones and A" -3,l 1,17-triones in acetic acid at room temperature in the presence of p-toluenesulfonic acid. In the case of thioketals the double bond remains in the 4,5-position. This result is attributed to the greater nucleophilicity of sulfur as compared to oxygen, which promotes closure of intermediate (66) to the protonated cyclic mercaptal (67) rather than elimination to the 3,5-diene [cf. ketal (70) via intermediates (68) and (69)]." " ... 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

The absolute configuration of the cycloaddition product obtained by the reaction of ketones with activated dienes catalyzed by (S)-t-Bu-BOX-Cu(II) (S)-21b points also to an intermediate in which the geometry around the central copper atom is square-planar similar to 26 above, and that the diene approaches the carbonyl functionality in an endo fashion. 

Dehydration of cortisone (198) affords the diene 199. This is then converted to ketal 200. The selectivity is due to hindrance about both the 11- and 20-carbonyl groups. The shift of the double bond to the 5,6-position is characteristic of that particular enone. Treatment of protected diene 200 with osmium tetroxide results in selective oxidation of the conjugated double bond at C-16,17 to afford the cis-diol (201). Reduction of the ketone at C-ll (202) followed by hydrolysis of the ketal function gives the intermediate 203. Selenium dioxide has been... 

Trapping reactions of benzoylmethyleneoxophosphorane 39 a with carbonyl compounds dispel any remaining doubts as to the existence of acylated phosphenes. Unlike the diphenylmethyleneoxophosphorane 9, whose P/C double bond participates in cycloadditions, compound 39 a acts as a hetero-1,3-diene and undergoes [4 + 2]-cycloaddition with aldehydes and ketones 10 I7,35> it may again be assumed that the reaction is a two-step process involving 55 as intermediate. 

Examples of the use of heterodienophiles under the action of microwave irradiation are not common. Soufiaoui [84] and Garrigues [37] used carbonyl compounds as die-nophiles. The first example employed solvent-free conditions the second is an example of the use of graphite as a susceptor. Cycloaddition of a carbonyl compound provided a 5,6-dihydro-2H-pyran derivative. These types of reaction proceed poorly with aliphatic and aromatic aldehydes and ketones unless highly reactive dienes and/or Lewis acid catalysts are used. Reaction of 2,3-dimethyl-l,3-butadiene (31) with ethyl glyoxylate (112) occurred in 75% yield in 20 min under the action of microwave irradiation. When conventional heating is used it is necessary to heat the mixture at 150 °C for 4 h in a sealed tube to obtain a satisfactory yield (Scheme 9.33). 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

The benzotriazolyl derivative of acrolein acetal, compound 882, is lithiated, treated with chlorodiphenylphosphine, and the obtained intermediate is oxidized with hydrogen peroxide to phosphine oxide 883 (Scheme 145). The relatively acidic proton in derivative 883 is easily removed by a base, and the obtained anion adds to a carbonyl group of aldehyde or ketone. Subsequent rearrangement and elimination of the phosphorane group generates diene 884. For the derivatives of aldehydes (884, R2 = H), (E)-(E) stereoselectivity of the elimination is observed. Acidic alcoholysis of dienes 884 affords esters of P,y-unsaturated carboxylic acids 885 < 1997JOC4131>. 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

The Peterson olefination reaction involves the addition of an a-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (awP -elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ,/l-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179. 

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