Enamines compounds

Scheme 64 to afford enamine compounds. The latter are isolated as the perchlorate salts by treating the reaction mixture with lithium perchlorate and water (69CB3176). 

Photoinduced [l,3]-acyl shift has also been found for Af-acylated isoquinolines and other enamine compounds ". ... 

The first stage produces the usual pyridoxal imine/enamine compound and decarboxylation gives a compound that can cyclize and give the cyclic iminiiim salt by loss of pyridoxamine. 

Enamines, compounds with a C=C tt bond adjacent to a C—bond, are formed through reaction of an aldehyde or a ketone with a secondary amine, most commonly pyrrolidine or morpholine. 

One extra disconnection is all we need to cope with misaturated heterocycles. If a nitrogen atom is joined to a double bond in a ring, we have a cyclic enamine. This is made from an amine and a carbonyl compound in the same way as ordinary enamines ... 

Another similar example concerns the alkylation of enamines. This reaction works well with reactive a-halocarbonyl compounds (frames 175ff) but simple alkyl hahdes often react on nitrogen ... 

A completely different, important type of synthesis, which was developed more recently, takes advantage of the electrophilicity of nitrogen-containing 1,3-dipolar compounds rather than the nucleophilicity of amines or enamines. Such compounds add to multiple bonds, e.g. C—C, C C, C—O, in a [2 + 3 -cycioaddition to form five-membered heterocycles. 

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

Typical nucleophiles known to react with coordinated alkenes are water, alcohols, carboxylic acids, ammonia, amines, enamines, and active methylene compounds 11.12]. The intramolecular version is particularly useful for syntheses of various heterocyclic compounds[l 3,14]. CO and aromatics also react with alkenes. The oxidation reactions of alkenes can be classified further based on these attacking species. Under certain conditions, especially in the presence of bases, the rr-alkene complex 4 is converted into the 7r-allylic complex 5. Various stoichiometric reactions of alkenes via 7r-allylic complex 5 are treated in Section 4. 

Application of 7r-allylpalladium chemistry to organic synthesis has made remarkable progress[l]. As deseribed in Chapter 3, Seetion 3, Tt-allylpalladium complexes react with soft carbon nucleophiles such as maionates, /3-keto esters, and enamines in DMSO to form earbon-carbon bonds[2, 3], The characteristie feature of this reaction is that whereas organometallic reagents are eonsidered to be nucleophilic and react with electrophiles, typieally earbonyl eompounds, Tt-allylpalladium complexes are electrophilie and reaet with nucleophiles such as active methylene compounds, and Pd(0) is formed after the reaction. 

Diacetates of 1,4-butenediol derivatives are useful for double allylation to give cyclic compounds. l,4-Diacetoxy-2-butene (126) reacts with the cyclohexanone enamine 125 to give bicyclo[4.3.1]decenone (127) and vinylbicy-clo[3.2.1]octanone (128)[85,86]. The reaction of the 3-ketoglutarate 130 with cij-cyclopentene-3,5-diacetate (129) affords the furan derivative 131 [87]. The C- and 0-allylations of ambident lithium [(phenylsulfonyl)methylene]nitronate (132) with 129 give isoxazoline-2-oxide 133, which is converted into c -3-hydroxy-4-cyanocyclopentene (134)[S8]. Similarly, chiral m-3-amino-4-hyd-roxycyclopentene was prepared by the cyclization of yV-tosylcarbamate[89]. 

Again, it is noteworthy that 4-substituted 5-hydrdxythiazoles (24) react like 5-hydroxy-THISs with alkynes to give pyrroles and sometimes with alkenes to give exo-cycloadducts (Scheme 22). In the latter case other processes compete with the cycloaddition, becoming dominant when 24 is treated with azo-compounds, enamines, or heterocumulenes (31). 

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

Cycloadditions of diazaquinones with unsaturated compounds yield diazacyc-lobutanes, from which N-substituted 3-hydroxypyridazin-6(l/f)-ones are formed after addition of water, t-butanol or acetic acid (Scheme 56). The same types of compound are also obtained from enamines. 

These compounds typically react with electrophiles on carbon and in this respect they resemble enamines, enol ethers and enol thioethers. For example, both pyrrole and 1-pyrrolidinocyclohexene can be C-acetylated (Scheme 4). 

The addition of 1,3-dicarbonyl compounds to /3-chloroazoalkenes is the basis of a pyrrole synthesis (Scheme 70a) 81TL1059). Pyrroles are also obtained by the reaction of enamines with azoalkenes (Scheme 70b) (79TL2969,81TL1475), and the copper(II) chloride catalyzed addition of 1,3-dicarbonyl compounds to arylazoalkenes (Scheme 70c) (82JOC684). 

Cationic rings are readily reduced by complex hydrides under relatively mild conditions. Thus isoxazolium salts with sodium borohydride give the 2,5-dihydro derivatives (217) in ethanol, but yield the 2,3-dihydro compound (218) in MeCN/H20 (74CPB70). Pyrazolyl anions are reduced by borohydride to pyrazolines and pyrazolidines. Thiazolyl ions are reduced to 1,2-dihydrothiazoles by lithium aluminum hydride and to tetrahydrothiazoles by sodium borohydride. The tetrahydro compound is probably formed via (219), which results from proton addition to the dihydro derivative (220) containing an enamine function. 1,3-Dithiolylium salts easily add hydride ion from sodium borohydride (Scheme 20) (80AHC(27)151). 

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Diazoalkanes add to the carbon-carbon double bonds of 2,3-diphenylthiirene 1-oxide and 1,1-dioxide. The adducts lose SO or SO2 to give pyrazoles and related compounds (Scheme 103) (80CB1632). Mesoionic oxazolones (75CLH53), 4-methyl-5-phenyl-l,2-dithiolene-3-thione (80JOU395) and pyrylium betaines (72JOC3838) react similarly via intermediate adducts (Scheme 104). Enamines (Scheme 96) and ynamines add to the double bond of 2,3-diarylthiirene 1,1-dioxides to give acyclic and cyclic sulfones by a thermal. 

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

Amino substituents on a carbon-carbon double bond enhance the nucleophilicity of the p carbon to an even greater extent flian the hydroxyl group in enols. This is because of the greater electron-donating power of nitrogen. Such compounds are called enamines. ... 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

A solution of 10 g of this compound in 80 ml of tetrahydrofuran is added, with cooling, during 5 min, to a solution of 4.8 g of lithium aluminum hydride in 60 ml of tetrahydrofuran, and the mixture refluxed for 2.25 hr then cooled in an ice bath and treated with 60 ml of acetone, followed by 200 ml of ether and 72 ml of 2 A sodium hydroxide. The mixture is filtered, the cake washed with 50 ml of acetone, and the combined filtrate washed with water, dried over sodium sulfate and evaporated under reduced pressure. The residue is crystallized from acetone to give 6.05 g (68 %) of the enamine. 

Tnalkylindoles undergoFnedel-Crafts reactions at position 6, however, in tnfluoroacetic anhydride the a-methyl group of 1,2,3-trimethylindole is acylated through an intermediate enamine [41, 42] (equation 27) Similarly, tnfluoroacetic anhydnde acylates the double bond of the a-methylene compound shown [42] (equation 28)... 

Enamines of an entirely different reactivity can be obtained by reacting compounds having co-hydroperfluoroalkyI chains with lithium diethylamide These... 

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