Aniline reaction with 1,3-dicarbonyls

Methylthiopyrimidine-4,5-dicarbonyl chloride 242, obtained by hydrolysis of the diester followed by reaction with oxalyl chloride, serves as a suitable starting material for the formation of 243 (Equation 87). The corresponding aniline and benzylamine were employed in the synthesis of 243a and 243b <2000MI19>. 

Carbanions from hydrocarbons, nitriles, ketones, esters, TV./V-dialkyl acetamides and thioamides, and mono and dianions from (3-dicarbonyl compounds are some of the most common nucleophiles through which a new C-C bond can be formed. This C-C bond formation is also achieved by reaction with aromatic alkoxides. Among the nitrogen nucleophiles known to react are amide ions to form anilines however, the anions from aromatic amines, pyrroles, diazoles and triazoles, react with aromatic substrates to afford C-arylation. 

Aminomethylene derivatives of ketones and 1,3-dicarbonyls are used in order to incorporate a formyl group into CH-acidic heterocycles via initial reaction with ethyl orthoformate and aniline followed by hydrolytic cleavage, as is shown e.g. with barbituric acid301 (equation 224). 

Ni(II)(OAc)2bpy and Co(II)(OAc)2bpy catalyze the Michael addition of nitro-methane, malononitrile, and aniline to a,j8-unsaturated ketones, methyl acrylate, and acrylonitrile in DMF under neutral conditions [116]. FeCls 6H2O is a highly efficient catalyst of Michael reaction of 1,3-dicarbonyl compounds with a,/3-unsaturated ketones under mild and neutral conditions (Sch. 24) [117]. There is literature precedent for this reaction with dual catalysis Ni(II) immobilized on a clay support and FeCl3 to activate the enone [118]. The mechanism proposed for the single-center catalysis involves coordination of the enone to a diketonato complex [119]. The chemo-... 

Indole-3-carboxylate esters and 3-acetylindoles can be prepared by palladium-catalyzed cycli-zation of enamines (14). These can be prepared from the corresponding anilines by condensation with j8-dicarbonyl compounds or by palladium-catalyzed substitution reactions with ethyl acrylate or methyl vinyl ketone <86BCJ927, 90S215>. Overall yields for the two-step process are 60-80% (Scheme 33). 

SCHEME 2.26 Proposed mechanism for the cyclization reaction a,P-unsaturated aldehydes 75 and aniline 51 with 1,3-dicarbonyl compounds 91 under chiral Brpnsted acid catalysis. 

More recently, a catalyst-free aqueous version of this strategy was proposed with simple acyclic 1,3-dicarbonyls, formaldehyde, and styrene or anilines derivatives (Scheme 40) [131], In the first case (Scheme 40), the very reactive 2-methylene-1,3-dicarbonyl intermediate reacts smoothly at 80°C with a variety of substituted styrenes to give the corresponding dihydropyrans in moderate to good yields. Remarkably, when styrenes were replaced by A-ethylaniline, a novel five-component reaction involving twofold excess of both formaldehyde and 1,3-dicarbonyl selectively occurred (Scheme 41). The result is the formation of complex fused pyranoquinolines following a Friedel-Craft alkylation - dehydration sequence to furnish the quinoline nucleus, which suffers the Hetero-Diels-Alder cyclization in synthetically useful yields. 

Solid-solid reactions 2.00 mmol of the 1,3-dicarbonyl compound 1 or 4 and 2.00 mmol of the solid aniline derivative 2 were ball-milled at room temperature for 30 min. After drying of the solid hydrates at 0.01 bar at 80 °C the pure enam-ine ketones 3 or 5 were obtained with quantitative yield. 

If cyclopentadienyliron dicarbonyl halides are allowed to react with themselves in the presence of Lewis acids, cations are formed in which the new substituent is the cyclopentadienyliron dicarbonyl halide itself, for example, [CjH6Fe(CO)i-X-(CO)2-FeC8H8]+ (X = Cl, Br, I). All three cations can be prepared best by treatment of the corresponding halides with boron trifluoride diethyl etherate all are isolated as tetrafluoro-borates.18 The bromine complex can also be obtained by a more complicated procedure by the reaction between C8H8Fe-(CO)2Br and AlBr3 in liquid sulfur dioxide 16 the iodine cation can be isolated from a melt of cyclopentadienyliron dicarbonyl iodide and aluminum chloride.17 In the latter two cases the hexafluorophosphate salts can be obtained. These binuclear cations are of special interest, because they are cleaved by electron donors,16-17 e.g., aniline, pyridine, benzonitrile, acetonitrile, acrylonitrile, with the formation of the corresponding [C8H8Fe(CO)2L]+ cations and the parent halide. Equations for preparation of the tetrafluoroborate are ... 

A more conventional reaction of ylides from /i-dicarbonyl precursors with some aniline tosylates furnished jV-arylated j3-dicarbonyl compounds [40],... 

---