Enamines cyano

Bis(trifluoromethyl)-substituted pyrimidines are also available fromtrifluoro-acetonitrde on reaction with enamines and ynamines [d ] With dimethylami-nocrotonates, a cyclocondensation takes place to give 2-pyridones. 5-Cyano-6-trifluoromethyluracil is available via a similar route [95] (equation 18)... 

The pyrrolidine enamine of 2-tetralone (177) was converted to l-cyano-2-tetralone, which exists almost entirely in the enolic form (178), by reaction with cyanogen chloride (J23). Reaction of 177 with cyanogen bromide gave N-naphthylpyrrolidine (179), presumably via the unstable bromoenamine (180). The latter observation is in accord with the mode of reaction of the heterocyclic enamine (126) with cyanogen bromide, which resulted in the... 

Enolate anions react with 3-cyano-4-methylfurazan giving enamines (Scheme 50) (75JAP(K)50049271, 77H1985, 78BCJ3059, 82H221). 

It is believed (54IZV47 72JPR353) that in the first stage the intermediate 282 is formed due to the addition of the CH acid to the enamine moiety with subsequent elimination of amine. The enol form of the intermediate 282 undergoes cyclization in two fashions, depending on the nature of substituent X. In the case of the ester (X = OMe) the attack is directed to the cyano group to form substituted 3-methoxycarbonyl-I//-pyridin-2-one (283) or its tautomer (2-hydroxy-3-methoxycarbonylpyridine). With the amide (X = NH2) intramolecular condensation leads to 3-cyano-l//-pyridin-2-one and its hydroxy tautomer (284). 

Reaction of ethyl (V-(cyanoacetyl)urethane with trifluoroacetonitrile gave 5-cyano-6-trifluoromethyluracil (85JOC4642). Trifluoroacetonitrile reacted with benzyl cyanide (86JOU1408) and diethyl malonate (89JHC7) to yield 2,6-bis(trifluoromethyl)pyrimidines. Cycloaddition of trifluoroacetonitrile with enamines having a /3-H offered a general route to 2,4-bis(trifluoromethyl)pyrimidines (84LA991). 

Natrium-cyano-trihydrido-borat reduziert Enamine in Methanol oder Metha-nol/Tetrahydrofuran (1 4) beipH5 (15-30 Min., 20°) zu gesattigten Aminen. Die konju-gierten Carbonyl-Gruppen in vinylogen Carbonsaure-amiden setzen die Reaktionsge-schwindigkeit herab. 

The Lewis acid catalyzed thermal [2 + 2] cycloaddition between 1-cyano-cyclopentene (68) and l-(N,N-diethylamino)-l-propyne (69) afforded the enamine... 

Coupling of the more activated enamine 335, obtained in two steps from tabersonine, with 21-cyano-20-epipandoline (331) in the presence of AgBF4 in THF solution gave the dimer 334 in 20% yield. Its structure was based on spectral data, particularly CMR. Diagnostic were the chemical shifts for C-2 at 104.1 ppm (versus 103.4 ppm in ervafoline) and the upfield shift of C-6 at 35.3 ppm (ascribed to the -y effect). 

At temperatures between -33and 0°C, l-cyano-l,2-allenes 574 can react with primary or secondary amines to afford unconjugated enaminic nitriles 575, which can be converted to conjugated enamines 576 at 200 °C [264, 265], The corresponding reaction of ammonia is relatively slow and was conducted at 60-70 °C to afford 3-amino-4-ethyl-2-hexenenitrile 577 together with a small precentage of iminyl nitrile 578 [264, 265],... 

The condensation of aldehydes and ketones with aminoacetonitriles, although it requires more vigorous soliddiquid catalytic conditions to produce the cyano-enamines, is preferable in many respects to the traditional Wittig-Horner or Peterson procedures [45]. Hydroxyalkylphosphonates are obtained from the catalysed aldol condensation of nitromethane with acylphosphonates [46]. 

Guertler et al. (1996) described a wide range of cycloaddition reaction between 2-vinyl indoles acting as heterodienes and cyclic or acyclic enamines bearing acceptor groups in (3 positions. The reaction was induced by the formation of 2-vinylindole cation-radicals through anodic oxidation. The synthesis of 4a-carbomethoxy-6-cyano-5,7-dimethylindolo[l,2-a]-l,2,3,4,4a,12a-hexahydro-1,8-naphthyridine can serve as an example (Scheme 7.24). 

In 2006, our research group reported a novel MCR based on the reactivity of a-acidic isocyano esters (1) toward 1-azadienes (84) generated by the 3CR between phosphonates, nitriles, and aldehydes [169]. Remarkably, the dihydropyridone products (85) for this 4CR contained the intact isonitrile function at C3. The exceptional formation of the 3-isocyano dihydropyridone scaffold can be explained by the Michael-attack of the a-deprotonated isonitrile (1) to the (protonated) 1-azadiene (84), followed by lactamization via attack of the ester function by the intermediate enamine. Although in principle the isocyano functionality is not required for the formation of the dihydropyridone (85) scaffold, all attempts using differently functionalized esters (e.g., malonates, ot-nitro, and a-cyano esters) gave lower yields of the dihydropyridone analogs [170] (Fig. 26). 

The reaction of or//io-substituted anilines containing substituent groups, e.g., phenyl, cyano, and nitro, gives rise to simple enamine fumarates these in turn can be cyclized to the corresponding 4-quinolones. " Aromatic diamines such as o-phenylenediamine and 2,3-diaminonaphthalene, however, react with DMAD to give tetra-hydroquinoxaline derivatives (7) [Eq. (2)]. ° It has been suggested that these tetrahydroquinoxalines exist in tautomeric equilibrium between the imine and enamine forms and that the enamine form (7) is more favored in inert organic solvents. On the other hand, an iso-... 

Enamines or imines can form pyridines by cyclization to a nitrile group, as shown in the production of compound (48). Alternatively, the nitrogen atpm of the nitrile can be made more nucleophilic by attack on the carbon atom by an external nucleophile. Ammonia causes cyclization of the dienamines (53) (77JHC1077) and (54) (78JAP(K)786878l) in both cases, elimination of the amine introduces the extra double bond. Dimethylamine or piperidine cause cyclization of l-cyano-2,5,5-trimethylhex-l-en-3-yne to the f-butyl-pyridine (55). There are a few other examples of the synthesis of bicyclic compounds from... 

The chiral a-cyano allylamines prepared from ( )-3-phenylpropenal, potassium cyanide and (L)-ephcdrinc [(17 ,2S )-2-methylamino-l-phenylpropanol] hydrochloride as a mixture (1 1) of C-l epimers, were deprotonated using 2 equivalents of LDA in THF to give the dilithio compound37. Alkylation at C-3 afforded regioselectively a mixture of (E)- and (Z)-enamines in variable amounts depending on reaction conditions. Diastereoselectivity varied from moderate to excellent. Addition of HMPA and especially lithium iodide improved the diastereoselectivity. De-aggregation is proposed to be the reason for the effect of these additives. 

The rearrangement of the 5-cyano-4,5-dihydro-l//-azepine (93) to furo[2,3-6]pyridine (95 Scheme 9) with sodium nitrate in glacial acetic acid or with silver nitrate in aqueous ethanol proceeds by initial protonation at either C-3 or C-6 followed by hydrolysis to the cyanooctanedione ester (94). By carrying out the rearrangement with an acid ion exchange resin it is now possible to isolate the dione ester (77CJC4061). Likewise, the hydrolysis of the tetrahydro-2-benzazepine (96) to an 0 -(anilinoalkyl)benzophenone is an example of proton attack at the /3 -carbon of the enamine system (77JA5045). 

Macrocyclic 2-pyrones (113) and (114) are prepared from enamine (115) and ketene (75HCA2409). Reduction of cyano ketone (116) with LAH affords an amino ketone which spontaneously cyclizes to generate a tetrahydropyridine (117) dehydrogenation by palladium on charcoal produces the aromatized phane (118) (71TL671). 

Enamines can be prepared from ot-cyano tertiary amines by treatment with KOH or f-BuOK in boiling benzene or toluene, or in f-butyl methyl ether at room temperature.262... 

An entire series of heterocyclizations is based on a-cyano-/3,/3-bis(acetyl)enamines (84JOC4696). When treated with weak bases, compounds 28 give amidine intermediates (29), which undergo cyclization yielding five-membered ring derivatives (30). The subsequent hydrolysis of 30 affords high yields of pyrrolinones (31). 

Numerous papers have been devoted to the synthesis of various derivatives of 2-pyridone, 4-pyridone, and aminopyridines based on enamines, di-enamines, dienediamines, and related compounds. For example, enamin-odiketones (153) can react with cyanoacetamide in tetrahydrofuran in the presence of sodium hydride with the formation of a substituted 3-cyano-2-... 

Enamine 204 reacts with cyanogen bromide with an unexpected result an aminocyanopyrimidine derivative 206 is the product. The reaction proceeds by the addition to the primary amino group with formation of compound 205 followed by cyclization and replacement of the trichloromethyl group by cyano group [85JCS(P1)1499],... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

---