Diketones, acid catalyzed reagents

The preparation of furans by acid catalyzed dehydration of 1,4-diketones followed by cyclization of the monoenol has been comprehensively reviewed (69RCR389). This method of furan preparation is useful for all 1,4-diketones which are not sterically hindered with the highly hindered l,4-bis(2,4,6-triisopropylphenyl)-l,4-butanedione no cyclization occurs (50JA5754). Although sulfuric acid is normally used for cyclization, hydrochloric acid was employed in the conversion of a 1,2-diacylethylene to a furylacrylic acid derivative (59MIP31200). Other reagents used for this purpose include polyphosphoric acid, phosphorus trichloride, zinc chloride and DMSO. Both DMSO and phosphoric esters provide neutral... 

Titanium trichloride fimctions as an excellent reductive Nef alternative reagent. This aqueous reagent is very acidic, so that acid sensitive groups such as ketals and esters do not survive unless an acetate buffer is used. Systems prcme to acid-catalyzed rearrangements may then successfully undeigo the reaction (equation 10).Some veiy sensitive multifunctional compounds have been obtained using this modified Nef procedure (equation 11). A related process is the formation of 1,4-diketones via in situ generation of a nitronatc anion by the Lewis acid catalyzed addition of an enol silyl ether to a nitroalkene (equation 12). ... 

Protection of 1,2-diols. These reagents are prepared from the diketones and HC(OMe)j in methanol containing a little sulfuric acid. By an acid-catalyzed exchange reaction, 2,3-dimethoxy-l,4-dioxane derivatives are formed in the reaction with 1,2-diols. Diequatorial diols are selectively protected. Actually, the protection can be performed directly by the reaction of a 1,2-diol with an a-diketone, trimethyl orthoformate, in methanol in the presence of camphorsulfonic acid. ... 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

In this synthesis of 1,5-dicaibonyl compounds, 3-butenyl halide is behaving as a madced 3-oxobutyl reagent, and can be used as an equivalent of metiiyl vinyl ketone. These reactirais offer new anellation methods. Also 1,4-addition of the allyl group to enones, followed by oxidatitm. offers a conveiuent synthetic method for 1,5-diketone preparation. Lewis acid promoted Nfichael addition of allylsilane (48) to a,p-unsaturated ketones, followed by the palladium-catalyzed oxidation, affods 1,5-diketones (Scheme 17). 3... 

A new synthetic method for steroids has been developed using a butadiene dimer (66) as a building block and the palladium-catalyzed oxidation as the key reaction.3-Acetoxy-l,7-octadiene (66), prepared by the palladium-catalyzed reaction of butadiene with acetic acid, is hydrolyzed and oxidized to l,7-octadien-3-one (67) in high yield. The enone (67) is a very useful reagent for bisanellation because its termiiud double bond can be regarded as a masked ketone which can be readily unmasked by the palladium catalyst to form the l,S-diketone (68) after Michael addition at the enone moiety of (67 Scheme 20). Thus, the enone (67) is the cheapest and most readily available bisanellation reagent, permitting a simple total synthesis of steroids. 

Methyl and methylene groups adjacent to carbonyl groups are easily oxidized to carbonyls to yield a-keto aldehydes or a-diketones. The reagent of choice is selenium dioxide or selenious acid. The reaction is catalyzed by acids and by acetate ion and proceeds through transition states involving enols of the carbonyl compounds [518]. The oxidation is carried out by refluxing the ketone with about 1.1 mol of selenium dioxide in water, dilute acetic acid, dioxane, or aqueous dioxane [517]. The byproduct, black selenium, is filtered off, but small amounts of red selenium sometimes remain in a colloidal form and cannot be removed even by distillation of the product. Shaking the product with mercury [523] or Raney nickel [524] takes care of the residual selenium. The a-dicarbonyl compounds are yellow oils that avidly react with water to form white crystalline hydrates (equations 407 and 408). 

Ireland and co-workers used a Wichterle sequence in their stereoselective syntheses of diterpenoid resin acids when annulations with methyl vinyl ketone resulted in polymeric tars. Stereoselective alkylation of cyclohexanone 34 with Wichterle s reagent afforded 35 as a single stereoisomer. Studies performed on this system determined that alkylation was favored cis to the C2 methyl group. After hydrolysis of the vinylic chloride 35 to the diketone 36, cyclization proved difficult due to the large amount of steric hindrance present in the molecule. Base-catalyzed cyclization resulted in only partial conversion to the desired octalone 37. It was found that a significant portion of the material was cleaved to the starting material for this sequence, monoketone 34, via facile reverse Michael addition when the side chain adopted an equatorial confirmation. 

Diels-Alder reactions are often very much accelerated by the presence of catalytic amounts of a Lewis acid, usually AlCl It was recently observed that some lanthanide tris-3 diketonates used as nmr shift reagents smoothly catalyze various Diels-Alder and hetero Diels-Alder reactions (eq. [38, 39j ). 

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