Diketones, acid catalyzed addition

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). ... 

The course of the acid catalyzed dehydration of 1,4-diketones to furans, known as the Paal-Knorr method (1884CB2756), entails the formal addition of the enol of one carbonyl group to the other carbonyl. Examples which illustrate some of the routes used to make the necessary 1,4-diketones are shown in Scheme 13. Few examples are known of the preparation of the other heterocycles by this general approach using isolated intermediates, although some of the ring closures discussed in Section 3.03.3.1.1 are mechanistically equivalent. One example of the preparation of a hydroxypyrrole is included in Scheme 13 <59AC(R)2075). 

The alternative to this 0,0-acetal formation is the sequence of addition and El reaction. As a matter of fact, this is familiar from the transformation of alcohols with carbonyl compounds, but only occurs in some (very rare) cases. This is illustrated by Figure 9.31 using acid-catalyzed transformations of ethanol with two /3-diketones as an example. Here, enol ethers, namely 3-ethoxy-2-cyclopentene-l-one and 3-ethoxy-2-cyclohexene-l-one, respectively, are... 

The Lewis acid promoted addition of allylsilane (48) to nitroalkene (47) gave the unsaturated ketone (49) after hydrolysis of the nitro group. The palladium-catalyzed oxidation affords the 1,4-diketone (50 Scheme 13). °... 

Biphenyl and alicyclic derivatives. Phosphoric acids (117) catalyzed addition of j8-diketones, jS-ketoesters, and vinylogous amides to a,j8-unsaturated aldehydes to give substituted chromenones, pyranones, and tetrahydroquinolinones in good yields, under mild reaction conditions, via a formal [3 -h 3] cycloaddition (Scheme 28). ... 

The first iodine-catalyzed synthesis of 2-alkyl substituted oxazoles 130 by a decarboxylative domino reaction was reported. Aryl methyl ketones 128 were transformed in situ into a-iodo ketones and then, by the Kornblum oxidation, into 1,2-diketones. After the addition of the a-amino acid 129, an l2-mediated cyclization/decarboxylation gave oxazoles 130. The reaction proceeds better if the Ar has electron-donating substituents and if the R group is a branched alkyl chain or phenyl residue. The reaction used oxone to regenerate iodine (13JOC6065). 

The Michael reaction is of central importance here. This reaction is a vinylogous aldol addition, and most facts, which have been discussed in section 1.10, also apply here the reaction is catalyzed by acids and by bases, and it may be made regioselective by the choice of appropriate enol derivatives. Stereoselectivity is also observed in reactions with cyclic educts. An important difference to the aldol addition is, that the Michael addition is usually less prone to sterical hindrance. This is evidenced by the two examples given below, in which cyclic 1,3-diketones add to o, -unsaturated carbonyl compounds (K. Hiroi, 1975 H, Smith, 1964). 

The base-catalyzed Michael addition of oxazolin-5-ones to alkynic ketones produces 4-(3-oxopropenyl) derivatives (405) (79CB3221). The latter compounds are cleaved on warming with oxalic acid dihydrate in acetic acid to y-diketones (406). The mechanism of this transformation corresponds to a vinylogous Dakin-West reaction (Scheme 90). 

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