Retro-Michael elimination

Crosslinking of amine- or hydroxy-terminated PAMAM dendrimers using cyclic anhydride - amine or cyclic anhydride - hydroxy addition reactions was employed for preparation of crosslinked thin films of very low permeability [73], Polyanhydrides, such as maleic anhydride-methyl vinyl ether copolymers, were used as crosslinking components. In the case of amine-terminated PAMAM, crosslinking and chemical stability were further increased by imidization of the maleamic acid groups retro-Michael eliminations were followed by Michael additions to further crosslink the film. 

Simple double aza-Michael reaction of divinyl ketones with primary amines was utilized to generate TV-substituted 3-phenyl-4-piperidones in good yields <07EJO4376>. In a somewhat similar mode, the diastereoselective synthesis of cyclic (3-amino esters by an Sn2 substitution-cyclization of an iodo-a,(3-unsaturated ester with (.Sj-u-mcthy 1 benzylamine was described <07OBC3614>. A combination intramolecular Michael-type addition followed by retro-Michael elimination was exploited in the generation of a phosphoryl dihydropyridone intermediate in the synthesis of /m .v-2,6-disubstitutcd 1,2,5,6-tetrahydropyridines <07JOC2046>. 

The yield of the cyclization step under the influence of a metal template can be increased when the corresponding dialdehyde 19 of the tetrapyrrole 16 is used. The reaction sequence is initiated by insertion of palladium(II) or nickel(II) into the tetrapyrrole to give 20 followed by Michael addition of one acrylaldehyde side chain to the other yielding the macrotetracycle 21 from which in a retro-Michael reaction acetaldehyde is eliminated to give 22. 

The combination of the carbonyl group and a / -hydroxyl group allows also the sugar to (a) dissociate in two smaller aldehydes, via the retro-Aldol reaction, or (b) eliminate the OH, via a retro-Michael reaction. 

Phenoxypropanoic acid, 3-(phenylthio)propanoic acid, 4-phenylbutanoic acid and the corresponding ethyl and methyl esters have been pyrolysed between 520 and 682 K.10 Analysis of the pyrolysates showed the elimination products to be acrylic acid and the corresponding arene. The thermal gas-phase elimination kinetics and product analysis have been found compatible with a thermal retro-Michael reaction pathway involving a four-membered cyclic transition state. 

Addition reactions. At low temperatures a,P-unsaturated acids behave as Michael acceptors toward RLi. The addition of benzenesulfonylmethyllithium to nitrones containing a vinyl group can lead to pyrrolidine Al-oxides after workup, due to a retro-Cope elimination which occurs at room temperature. ... 

Another aspect to Rogers s work on the synthesis of unsymmetrical hydroxylamines (Section 4.2.5.1) is that the elimination step is base catalyzed (occurring at room temperature).16 Salts of amine oxides derived from P-aminopropionic esters 45 or nitriles 46 undergo the reaction, which involves a retro-Michael addition, facilitated by the formal positive charge on nitrogen. 

The aza-Morita-Baylis-HiUman reaction is known to be a useful and atom-economical C-C bond-forming reaction of electron-deficient alkenes with imines usually catalyzed by Lewis bases [202]. It formally involves a sequence of reactions including a Michael addition, a Mannich reaction, a proton transfer, and a retro-Michael reaction ( -elimination). Although there are many reports in the field of the enantioselective aza-Morita-Baylis-Hilhnan reaction, only rare examples of asymmetric domino reactions initiated by this reaction have been reported. In 2010, Sasai et al. [203] developed the first organocatalyzed asymmetric domino aza-Morita-Baylis-Hillman/aza-Michael reaction of a,p-unsaturated carbonyl compounds with N-tosylimines, allowing an easy access to chiral cis-1,3-disubstituted isoindolines as single diastereomers. The process was induced by a Hg-BINOL-derived catalyst and provided these products in high yields and enantioselectivities, as shown in Scheme 10.18. 

The steps in the formation of 5-hydroxymethyl furfural (HMF) from 1,2-enediol is shown in Formula 4.37. HMF is also used as an indicator for the heating of carbohydrate containing food, e. g., honey. The (retro-Michael addition) water elimination at C-3 and subsequently at C-4 leads to a 1,2-diulose (3,4-dideoxyosone), which after cyclization to a hemiacetal, a dihy-drofuran, releases another molecule of water, producing HMF. In the same way, e. g., furfural can be made from pentoses and 5-methylfurfural from the 6-methylpentose rhamnose. 2-Hydroxyacetylfuran, which is preferentially formed from fructose, can be obtained starting from the corresponding 2,3-enediol by water elimination at C-4, followed by C-5 (Formula 4.38). 

Like the corresponding 2,3-enediol, the 2,3-eneaminol has two different P-elimination options. Formula 4.56 shows the elimination of the amino acid by a retro-Michael reaction with... 

It should be noted that cleavage of the C -Cp bond of the alkyl cyanide 110 to the nitrile 111 has been reported (Scheme 6.25) [81]. This transformation is a formal retro-Michael-type fragmentation, but proceeds under neutral conditions. Oxidative addition of an a-C-H bond followed by P-carbon elimination is suggested. 

Because aldolase antibodies operate by an enamine mechanism, they also catalyze other reactions that proceed by a similar mechanism. For example, as described in the section on prodrug activation reactions, antibodies 38C2 and 33F12 catalyze / -elimination (retro-Michael) reactions (Section 6.3.6). These antibodies also catalyze decarboxylation of j5-keto acids (Scheme 6.12)... 

The reaction of 11 with ordinary alkenes with a Cu(OTf)2 catalyst gave 1,2-dihydronaphthalenes. However, reaction with p-methoxystyrene 8 afforded the naphthalene derivative 12 in 83% yield. Probably, retro-Michael addition occurred and the methoxy group was eliminated as methanol [24], This protocol can be applied to the formation of benzo-fused heteroaromatic compounds such as indols 35 and benzofuranes (Scheme 15.13) [25]. 

These amines gave, with methyl propiolate, products of Michael mono- and bis-addition. Adducts underwent further reaction leading to triazolo[4,5-/]quinolones 181, after retro Diels-Alder reaction and acetylene elimination to its methoxycar-... 

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