With aldehydes

In 2006, Lectka and coworkers reported an asymmetric inverse electron demand hetero-Diels-Alder reaction (HDAR) of acyl chlorides (Bekele et al. 2006 Wolfer et al. 2006) and o-benzoquinone diimides to deliver chiral quinoxalinones (Abraham et al. 2006). In spite of perfect ee values observed by the catalysis of Lewis bases derived from cinchona alkaloids, the reaction conditions were somewhat harsh and metal triflates had to be used as co-catalysts to activate the electrophilic o-benzoquinone diimides (Abraham et al. 2006 Pauli et al. 2(X)8). 

Since the required o-benzoquinone diimide was easily accessible by benzoyla-tion of commercially available 1,2-DAB derivative and subsequent oxidation, it appears possible that a search for more appropriate methods of carrying out HDAR to synthesize chiral quinoxaline derivatives would be fruitful. 

When the HADR was carried out as in the previously established conditions (Han et al. 2008) o-benzoquinone diimide 268 (1.0 equiv), butanal 253e (2.0 equiv), benzoic acid (10 mol%), and the catalyst a,a-diphenylprolinol 0-TMS ether 269 (10 mol%) in a mixture of MeCN and H2O (10 1) at room temperature, the reaction proceeded smoothly and the desired hemiaminal 270 was isolated as a 

In the context of the discussion above, it should be noted that the oxidative transformation of 1,2-DAB 155a with air as an oxidant in the presence of catalytic amounts of laccase from Agaricus bisporus delivers exclusively 

4- addition to yield a tetrahydrophenazine 274. The last step is the oxidation of this intermediate to afford the fully aromatic 2,3-diaminophenazine 272. On an 

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Brady s reagent A solution of 2,4-dinitro-phenylhydrazine sulphate in methanol. Gives characteristic crystalline yellow to deep red 2,4-dinitrophenylhydrazone products with aldehydes and ketones. 

Greenish-yellow needles or prisms, m.p. 148-149 C, sparingly soluble in cold water. Gives crystalline condensation products with aldehydes. 

Girard s reagents Quaternary ammonium salts of the type Me3NCH2CONHNH2 X which form water-soluble compounds with aldehydes and ketones, and are therefore separable from other neutral compounds the aldehyde or ketone may be subsequently regenerated after separation. 

Resins formed from the reaction of poly(vinyl alcohol) with aldehydes. The formal derivative (from methanal) is used in wire coatings and adhesives and the bulyral (from butanal) is used in metal paints, wood-sealers, adhesives and in safety glass interlayers. 

NH2-C0-NH NH2,CH5N30. Colourless crystalline substance m.p. 96" C. Prepared by the electrolytic reduction of nitrourea in 20% sulphuric acid at 10 "C. Forms crystalline salts with acids. Reacts with aldehydes and ketones to give semicarbazones. Used for the isolation and identification of aldehydes and ketones. 

Sodium hydrogensulphite, when freshly prepared, reacts with aldehydes to form crystalline addition compounds, for example... 

Phenyl hydrazine condenses readily with aldehydes and ketones to give phenylhydrazonesy which, being usually crystalline compounds of sharp... 

Reagent B is valuable for use with aldehydes or ketones which are insoluble in water, and therefore unsuitable for treatment with Reagent A cf. benzaldehyde, p, 342 benzophenone, p. 346). It is much more concentrated than A, and consequently can be more readily used for the isolation and purification of the required hydra2one. 

Dimedone derivatives. Dimedone or 6 6-dimethylci/cZohexane-1 3 dioiie j- in saturated aqueous solution J or in 10 per cent. alcohoUc solution gives crystalline derivatives (I) with aldehydes, but not with ketones. The reaction is ... 

Examples of the Knoevenagel reaction with aldehydes are given under crotonic acid (111,145), P-n-hexylacrylic acid (111,144), sorbic acid (111,145) and furylacryUc acid (V,10). 

If an unknown compound gives a positive test with the 2 4-dinitrophenylhydrazine reagent, it then becomes necessary to decide whether it is an aldehyde or a ketone. Although the dimedone reagent (Section 111,70,2) reacts only with aldehydes, it is hardly satisfactory for routine use in class reactions. It is much simpler to make use of three other reagents given below, the preparation and properties of which have already been described (Section 111,70). 

Lewis acid promoted condensation of silyl ketene acetals (ester enolate equiv.) with aldehydes proceeds via "open" transition state to give anti aldols starting from either E- or Z- enolates. 

Ene reaction with aldehydes is catalyzed by Lewis Acids (Et2AlCl)... 

Trimethylsilylation with trimethylchlorosilane affords the corresponding allene derivative, hydroxyalkylation with aldehydes and ketones gives mixtures of comparable amounts of acetylenic and allenic carbinols. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

The Q. j-unsaturated ester and amide 942 is prepared by the Pd-catalyzed Wittig-type reaction of the bromoacetate or bromoacetamide 941 with aldehydes and BU(Asf785],... 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

In 1884, Nencki (70), studying the properties of rhodaninic acid, confirmed the formula proposed by Libermann and Lange (39) and noted its ability to condense with aldehydes. 

In 1886, Ginsburg and Bondzynski (71) and Berlinerblau (72) developed the reaction of rhodanine with aldehydes, but proposed a chain formula for the condensation product. 

During a relatively long period, the condensation of rhodanines with aldehydes was developed, especially by Andreasch s group (78-87). Finally, Holmberg (88, 89) described the best method to obtain rhodanines the condensation of ammonium dithiocarbamate with a sodium or potassium salt of an a-chloro acid. 

The 2-metalated thiazoles react with a variety of electrophilic substrates in a standard way, leading to addition products with aldehydes, ketones, carbon dioxide, epoxides, nitriles, Schiff bases, and to substitution products with alkyl iodides (12, 13, 437, 440). 

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