Ketones Michael acceptors

Buten-2-one (Methyl vinyl ketone) (Michael acceptor)... 

Methyl vinyl ketone 2 tends to polymerize, especially in the presence of a strong base the yield of annulation product is therefore often low. A methyl vinyl ketone precursor, e.g. 6, is often employed, from which the Michael acceptor 2 is generated in situ, upon treatment with a base. The quaternary ammonium salt 6 can be obtained by reaction of the tertiary amine 5, which in turn is prepared from acetone, formaldehyde and diethylamine in a Mannich reaction. 

Besides a polymerization of the Michael acceptor, a double alkylation of the starting ketone, by reaction with a second Michael acceptor molecule, may take place as a side reaction, and thus further reduce the yield. The polymerization of the enone 2 as well as the double alkylation of the starting ketone can be avoided by application of a modern procedure for the Robinson annulation that uses an organotin triflate as catalyst." ... 

Since most often the selective formation of just one stereoisomer is desired, it is of great importance to develop highly selective methods. For example the second step, the aldol reaction, can be carried out in the presence of a chiral auxiliary—e.g. a chiral base—to yield a product with high enantiomeric excess. This has been demonstrated for example for the reaction of 2-methylcyclopenta-1,3-dione with methyl vinyl ketone in the presence of a chiral amine or a-amino acid. By using either enantiomer of the amino acid proline—i.e. (S)-(-)-proline or (/ )-(+)-proline—as chiral auxiliary, either enantiomer of the annulation product 7a-methyl-5,6,7,7a-tetrahydroindan-l,5-dione could be obtained with high enantiomeric excess. a-Substituted ketones, e.g. 2-methylcyclohexanone 9, usually add with the higher substituted a-carbon to the Michael acceptor ... 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

Keywords Facial selection. Orbital phase, Secondary orbital interaction. Orbital unsymmetrization. Ketones, Olefins, Diels-Alder dienophiles, Diels-Alder dienes, Michael acceptor. Amine nitrogen atom... 

OS 52[ [OS 53[ [OS 54[ [OS 55[ [R 4b[ [P 38[ In a two-micro-mixing tee chip reactor, substrates with diketone moieties of known different reactivity, such as 2,4-pentanedione, benzoylacetone and diethyl malonate, were processed, each with the same acceptor ethyl propiolate [8]. Also, a reaction with the less alkynic Michael acceptor methyl vinyl ketone was carried out. 

Among Michael acceptors that have been shown to react with ketone and ester enolates under kinetic conditions are methyl a-trimethylsilylvinyl ketone,295 methyl a-methylthioacrylate,296 methyl methylthiovinyl sulfoxide,297 and ethyl a-cyanoacrylate.298 Each of these acceptors benefits from a second anion-stabilizing substituent. The latter class of acceptors has been found to be capable of generating contiguous quaternary carbon centers. 

Michael reaction of enamines of u-alkyl- -keto esters. The chiral lithioen-amine (1), prepared from (S)-valine /-butyl ester, does not react with methyl vinyl ketone or ethyl acrylate unless these Michael acceptors are activated by ClSi(CH3)3... 

Due to the strong electron-withdrawing ability of the carbonyl group, a 1,2-allenyl ketone is a very good Michael acceptor. Hence it can undergo 1,4-addition with all kinds of nucleophiles. 

Using methyl vinyl ketone as Michael acceptor, it was found (42) that a variety of donors gave optically active products when quinine was used as the chiral catalyst. Figure 7 lists the donors. Unfortunately in none of these cases... 

Reactions involving ketones are generally controlled by the thermodynamic stability of the enolate anion. However, 2-phenylcyclohexanone reacts with bulky Michael acceptors to form the 2,6-regioisomer preferentially [17], indicating that the reaction is mainly kinetically controlled with the approach of the Michael acceptor to the substituted 2-position being sterically hindered. 

Also known as Morita-Baylis-Hillman reaction, and occasionally known as Rauhut-Currier reaction. It is a carbon—carbon bond-forming transformation of an electron-poor alkene with a carbon electrophile. Electron-poor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. On the other hand, carbon electrophiles may be aldehydes, a-alkoxycarbonyl ketones, aldimines, and Michael acceptors. 

The product of a Michael addition depends on the number of acidic protons present in the nitroalkane substrate. Nitroform, which has one acidic proton, can only react with one equivalent of Michael acceptor. Nitroform is a strong acid and sufficiently dissociated in solution so that it can be used in addition reactions without a base catalyst. The reaction of nitroform with unsaturated ketones has been investigated by Gilligan and Graff and used to synthesize a number of trinitromethyl-based explosives. 

Aliphatic compounds containing terminal gem-dinitro functionality form adducts with Michael acceptors.Of particular interest is the reaction of a,a,o),a)-tetranitroalkanes with Michael acceptors. ° Most a, o, y, y-tetranitroalkanes will react with two equivalents of Michael acceptor to form bis-adducts, like in the case of 1,1,4,4-tetranitrobutane, which reacts with two equivalents of methyl vinyl ketone, methyl acrylate, acrylonitrile etc. ° The influence of steric effects becomes apparent with a,a,y,Y-tetranitroalkanes, like 1,1,3,3-tetranitropropane, which can form either mono-adducts or bis-adducts depending on the Michael acceptor used 1,1,3,3-tetranitropropane will only react with one equivalent of methyl acrylate and the sole product of this reaction is methyl 4,4,6,6-tetranitrohexanoate. °... 

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