Benzyliden-1,3 -dicarbonyl compounds

The ds-selechvity of the Diels-Alder reachon using aromahc aldehydes is demonstrated in the reachon of aldehydes such as 2-746, which contain a dienophile moiety. Treatment with N, N-dimethylbarbituric acid (2-747) in the presence of ethylene diammonium diacetate at 20 °C led to the ris-fused product 2-749 exclusively in 95% yield (Scheme 2.164) [377]. As an intermediate, the benzylidene-1,3-dicarbonyl compound ( )-2-748 is formed, which can be identified using online NMR-... 

The alkylidene- or benzylidene-1,3-dicarbonyl compounds formed in the Knoevena-gel condensation of aldehydes or ketones with 1,3-dicarbonyls, can act not only as a... 

Aromatic aldehydes react very easily with tetramic acid under acidic conditions to give 3-benzylidene compounds (41). The yields are moderate, because often there are subsequent reactions. As a,/3-unsaturated carbonyl compounds, (41) react in a Michael addition with excess tetramic acid to form (67), but it can also react with other acyclic and cyclic 1,3-dicarbonyl compounds. In these reactions the aryl substituents may vary over a wide range. Thus, (67) and (68) can be cyclized with ammonium acetate to afford pharmacologically interesting compounds (70) and (71) (90TH1). The latter are dihydropyridines. Curiously, (69) does not cyclize under these conditions. (See Fig. 32.)... 

The importance of fluorinated organic componnds both in medicinal chemistry and biochemistry has resulted in much recent attention towards efficient carbon fluorine bond formation [30]. The reactions developed include a very successful electrophilic asymmetric mono-fluormation of 1,3-dicarbonyl compounds [31]. A nucleophilic variant was also investigated. In this context, the groups of Togni and Mezzetti have established that ruthenium Lewis acids could efficiently catalyze fluorination reactions [32]. In the presence of [Ru(l,2-bis(diphenylphosphino)ethane)2Cl][PF6] (8) (10 mol%), fert-butyl iodide reacted at room temperature with TIF (1.1 equiv.) to yield fert-butyl fluoride (84% yield). This reaction was extended successfully to a range of organic halides (Entries 1-3, Scheme 10.19). The use of the chiral complex [Ru((lS,2S)-N,N bis[2-diphenylphos-phino)benzylidene]diaminocydohexane))Cl][PF6] (9) showed modest chiral induction at the outset of the reaction (Entry 4, Scheme 10.17). The near-racemic mixture obtained at completion points to an SNl-type process in this nucleophilic halide... 

Reactions of Enols and Enolate Anions.—Several methods are described for transposition of an oxo-function to the adjacent site. They involve formation of a suitable a-substituted derivative (hydroxymethylene ° or benzylidene ) and subsequent steps which transform the substituent into an isolated oxo-group. Condensations leading to both the 2-hydroxymethylene- and the 2-arylidene-3-oxo-steroids are described for 3-ketones of the 5jS-series, and also of the 5j8,9j5,10a-( retro ) series.Condensations of aromatic aldehydes at C-2 in the 5 -series are unusually slow enolisation towards C-4 is preferred, but steric compression between C-4 and C-6 in 5/3-compounds severely hinders the condensation reaction at C-4, allowing reaction at C-2 via the 2-enol. Reduction of a 21-hydroxymethylene-pregnan-20-one (337) with sodium borohydride afforded the homopregnanediol (338), although reduction of enolised P-dicarbonyl compounds frequently proceeds via elimination to give enones, and thence allylic alcohols. 

An example for a change of mechanism in a chemoselective reaction by applying high pressure is the transformation of the benzylidene-l,3-dicarbonyl compound... 

In modifications of the Hantzsch synthesis [65], P-enaminones replace one molecule of the P-dicarbonyl compound, and enones undergo cyclocondensation with P-enaminones or 1,5-dicarbonyl compounds with NH3. Thus, for instance, as an alternative to the classical synthesis (2 mol acetoacetate, benzaldehyde and NH3), the l,4-dihydropyridine-3,5-dicarboxylate 171 is obtained from acetoacetate, benzaldehyde and p-aminocrotonate (1 1 1), as well as from benzylidene acetoacetate and aminocrotonate (1 1). 

A strategy has been reported to control the product distribution of the reaction of O -benzylidene-/S-dicarbonyl compounds and diazoacetate for the selective synthesis of either dihydrofurans or dihydrobenzoxepines from identical starting materials (Scheme 72) ... 

Amino-2-deoxy-D-gluconic acid and its, 6-0 -benzylidenated ethyl ester gave enamines, e.g.,(69).on reaction with 3-dicarbonyl compounds these could be lactonized and dehydrated to a,B-unsaturated lactones,e.g.,(70).and thence converted into pyranones e.g.,(71).(Scheme 15). °... 

A study of the Michael addition of ester enolates R CH=C(OLi)OR to a-benzylidene and a-alkylidene -dicarbonyl compounds, for example, R CH=C(C02Me)2, has demonstrated that the diastereoselectivity depends on the substitution pattern of the Michael acceptor and the geometry of the enolate, which in turn can be controlled by the method of their generation (i.e. EDA in THF vs EDA and HMPA in THF). Thus, (E)-enolates exhibit iyn-diastereoselectivity, whereas (Z)-enolates afford the anti-diastereoisomers. Eow stereocontrol was observed with unsaturated nitriles and Meldrum s acid derivatives. A stereochemical model has been proposed to accounts for all experimental results. ... 

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