Enone derivatives amination reactions

Tertiary amines have also been employed in electron transfer reactions with a variety of different acceptors, including enones, aromatic hydrocarbons, cyanoaro-matics, and stilbene derivatives. These reactions also provide convincing evidence for the intermediacy of aminoalkyl radicals. For example, the photoinduced electron transfer reactions of aromatic hydrocarbons, viz. naphthalene, with tertiary amines result in the reduction of the hydrocarbon as well as reductive coupling [183, 184]. Vinyl-dialkylamines can be envisaged as the complementary dehydrogenation products their formation was confirmed by CIDNP experiments [185]. 

Aziridinations of enones using Cinchona-hased phase-transfer conditions are so far rare and have not been as successful and generally applicable as is the case for epoxidation reactions. In contrast, iminium catalysis using primaiy Cinchona-derived amines again provided excellent solutions for enone aziridination. 

It has been shown that addition of catalytic amounts of TBAF (0.02 equiv.) to A-(trimethylsilyl)imidazole promotes the quantitative silylation of alcohols in complex polyhydroxy compounds under milder conditions. The reaction proved to be highly chemos-elective, with other functional groups like ketones, enones, epoxides, amines or carboxylic acids being unreactive under these conditions. The silylation of a complex derivative that could not be achieved without TBAF was effected in 1 h (eq 1 ) ... 

In the second reaction, a Michael-Michael cascade between an unsaturated oxin-doles 17 and enones 22 was shown to be catalyzed by a primary amine-derived catalyst (II) (Scheme 10.3). The reaction afforded the spirooxindoles 23 in excellent yields and diastereo and enantioselectivities. Wang used a similar approach in the reaction of isatylidene malononitriles and enones [12]. The reaction was catalyzed by the dual combination of cinchona-based chiral primary amine and BINOL phosphoric acids to afford the spirocycles in excellent yields (88-99%), diastereo (up to 99 1 dr), and enantioselectivities (95-99% ee). 

Since heterocycles containing a trifluoromethyl group are representatives of a major structure type in agricultural and medicinal chemistry, Shibata et al. have developed a novel enantioselective synthesis of trifluoromethyl-substituted 2-isoxazoHnes 46 on the basis of a domino oxa-Michael—intramolecular hemi-aminalization-dehydration reaction of hydroxylamine with a range of (B)-trifluoromethylated enone derivatives 47 [81]. This process, which employed N-3,5-bis(trifluoromethyl)benzyl-quinidinium bromide 48 as a chiral phase-transfer catalyst combined with CsOH as a base provided a series of trifluoromethyl-substituted 2-isoxazolines 46 in high yields and enantioselectivities of up to 94% ee (Scheme 37.8). 

The amine-catalyzed Diels-Alder dimerization reaction of a, 3-unsaturated ketones in water was developed by Barbas et al. to form cyclohexanone derivatives (Eq. 12.12). They believe that the reaction proceeds via the in situ formation of 2-amino-1,3-butadiene and iminium-activated enone, as the diene and dienophile, respectively. 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

The reaction of potassium dienoxy borates with A-fluorobis(phenylsulfonyl)amine (la) gives y-fluoro enones in good yield. The potassium dienoxy borates are prepared by treating potassium enolates derived from unsaturated ketones with 2-phenyl-1,3,2-benzodioxaborole. This methodology offers a convenient alternative to the traditional fluorination of dienol acetates, ethers, or enamines.145 An example is given by the formation of 13.145... 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

Another concise route to 107 featured the facile construction of the cyclohexanone derivative 109 via the Michael addition of triply deprotonated methyl dioxohexanoate to the nitrostyrene (108 (Scheme 9) (115). Ketalization of 109 followed by hydrogenation of the nitro function and then cyclization of the resulting amino ester by thermolysis in refluxing xylene furnished the lactam 110, which was reduced LiAlH4 to the amine 111. All attempts to cyclize 111 via a Pictet-Spengler reaction led to complex mixtures of products. However, when the unstable enone 112, which was obtained by acid-catalyzed hydrolysis of 111,... 

Shi and Xu reported that the chiral amine catalyst 142 also performs quite efficiently in the related addition of N-tosyl aryl imines to methyl vinyl ketone (MVK), to methyl acrylate, and to acrylonitrile (Scheme 6.61) [155]. As shown in Scheme 6.61, enantiomeric excesses > 95% were achieved for several />-N-tosylamino enones 147 obtained by addition of aryl imines (146) to MVK, > 80% for addition to methyl acrylate, and 55% ee (max.) for addition to acrylonitrile (not shown in Scheme 6.61). Reaction times were typically 1-3 days. N-Sulfonylimines derived from aliphatic aldehydes gave rise to complex product mixtures. Under the reaction conditions shown in Scheme 6.61 addition of p-nitrobenzaldehyde to MVK proceeded with only 20% ee. 

Another approach involves the use of an electron-poor olefin acting both as an absorbing electron acceptor and as a radical trap. In this case, a PET reaction between a cyclohexenone derivative and a silylated amine led to a radical ion pair. Desilylation of the silyl amine radical cation intermediate in polar protic solvent (e.g., MeOH) and subsequent aminoalkyl radical attack onto the enone radical anion yielded the alkylated cyclohexanones [23]. 

By using the substrates involving both formyl and enone moieties, a tandem reaction of reductive amination Michael addition gives isoindoline derivatives (Equation (26)). 

The nucleophilic capture of the trichlorocyclopropenium ion is not restricted to aromatics. In fact treatment of tetrachlorocyclopropene with secondary amines and thiols results in tris-amino- and thio- cyclopropenium ions, e.g. 76. One advantage of such species is in their reaction with nucleophiles, e.g. HO", which deliver the corresponding sp -hybridized derivative, e.g. enone 77, by an addition-elimination sequence The transammination reaction, initially performed in good-to-excellent yields with secondary amines, often employs a trimethylsilylamine which has allowed for the synthesis of the tris-(mono-organylamino)cyclopropenium salt (76a) in almost quantitative yield. 

Tosylmethyl isocyanide (TosMIC) (75 R = H), a versatile reagent in synthesis, can also be used as an acyl anion equivalent. For instance symmetrical and unsymmetrical diketones were prepared by using this TosMIC synthon (equation 40). Ketones are homologated to enones by alkylating the condensation product derived from TosMIC, followed by acid hydrolysis (Scheme 46). 1-Isocyano-l-tosyl-l-alkenes (76), formed by the reaction of TosMIC with an aldehyde or ketone, react with a primary amine or ammonia to give 1,5-disubstituted (or 5-monosubstituted) imidazoles in high yield (Scheme 47). ... 

The aza-ene reaction recently found application in the synthesis of imidazo[1,2-a]pyridine and imidazo[1,2,3- y][1,8]naphthyridine derivatives in the laboratory of Z.-T. Huang.The reaction of heterocyclic ketene aminals with enones such as MVK proceeded via an aza-ene addition, followed by intramolecular cyclization to afford the products. The aroyl-substituted heterocyclic ketene aminals (Ar=Ph, 2-furyl, 2-thienyl) underwent two subsequent aza-ene reactions when excess MVK was used. 

Boron or tin (II) Z-enolates are generated by reaction with the corresponding triflates with a carbonyl compound in the presence of tertiary amines like r-P NEt or. M-ethylpiperidine (except when using dicyclopentylboron triflate [407]). E-Enolates are prepared by using dicyclohexyl- or other cyclic chloroboranes in the presence of Et3N or Me NEt [407, 685, 686, 1246, 1247, 1248], Because enolization does not take place under such conditions with esters or aliphatic tertiary amides, thiophenyl esters RGH COSPh have been used as ester/amide substitutes. Furthermore, Z-boron enolates of ketones can be prepared by conjugate addition of acid derivatives of dialkylboranes to a-enones [687],... 

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