Enamine products

Unsaturated sulfoncs (314,315) and nitroolcfins (303,315-317) also give alkylation products with enamines. In the latter reactions the formation of nitroethyl or cyclobutane derivatives has been found (316) to depend on the reaction medium as well as steric and electronic parameters which determine the fate of zwitterionic intermediates. Thus no enamine products could... 

In the reactions of benzyne with enamines, arylated enamines or amino-benzocyclobutenes can be obtained, depending on reaction conditions and the structure of the enamine. Thus the presence of a proton source such as a secondary amine will favor the enamine product through capture of the zwitterionic intermediate, whereas in the absence of protons one sees... 

Loss of a proton from the alpha carbon atom yields the enamine product and regenerates the acid catalyst. 

The r] a-amino-organolithium species shown in Scheme 66 react with several different electrophiles at the y-position relative to the nitrogen atom. With benzyl bromide, electrophilic substitution is invertive, but with enones and ketones, it is retentive (Scheme 67). Reversal of steric course between CO2 (Sg2inv) and ClC02Me (Sg2ret) is also observed in this system (compare Scheme 64). Hydrolysis of the enamine products affords /3-substituted aldehydes that can be further elaborated. " ... 

It is possible to arrest the workup to provide the enamine product ... 

The overall reaction is best viewed as intramolecular oxidative addition of the C(l)—H bond to the Rh(I) center, causing cyclometalation (25), followed by reductive elimination of an enamine from the Rh(III) intermediate accompanied by allylic transposition. Notably, the allylamine ligand in the initial Rh(I) complex as well as the Rh(III) intermediate has an s-trans conformation with respect to the N—C(l) and C(2)—C(3) bonds, allowing the overall suprafacial 1,3-hydrogen shift to produce the is-configured enamine product. 

There are rather few reactions that can be described as fully atom economical , i.e. when there are no co-products and all the atoms in the starting material(s) appear in the product(s). However, all isomerisation reactions necessarily fall into this category. The use of a transition metal to catalyse such a process with an appropriate substrate brings the possibility of effecting asymmetric isomerisation, a very efficient method to generate enantiomerically enriched products. Indeed, the asymmetric Rh-catalysed isomerisation of an allylamine to an enamine, which proceeds in over 96% ee, was scaled up a number of years ago for industrial production. The enamine product forms a multi-tonne feedstock for menthol and perfumery synthesis. In contrast, the cyclo-isomerisation of dienes, an equally atom-economical process that generates synthetically useful cyclic products, has seen relatively little development despite the reaction having been known for some 30 years. 

The reaction with 1-azabutadiene is also unfavorable for other reasons. To begin with, the 4 + 2 cyclization is inherently less exothermic than with 2-azabutadiene (see Exercise 20, p. 123). Furthermore, the enamine product will rapidly undergo side-reactions with adventitious electrophiles. An imine-enamine tautomerism which transforms R-N=CH-CH=CH-CH3 into RNH-CH=CH-CH=CH2 also contributes to lowering the yield. Finally, electron-poor dienophiles may undergo a competing reaction with the nitrogen lone pair. 

MacMillan s catalysts 56a and 61 allowed also the combination of the domino 1,4-hydride addition followed by intramolecular Michael addition [44]. The reaction is chemoselective, as the hydride addition takes place first on the iminium-activated enal. The enamine-product of the reaction is trapped in a rapid intramolecular reaction by the enone, as depicted in Scheme 2.54. The intramolecular trapping is efficient, as no formation of the saturated aldehyde can be observed. The best results were obtained with MacMillan s imidazolidinium salt 61 and Hantzsch ester 62 as hydride source. As was the case in the cyclization reaction, the reaction affords the thermodynamic trans product in high selectivity. This transformation sequence is particularly important in demonstrating that the same catalyst may trigger different reactions via different mechanistic pathways, in the same reaction mixture. 

We have also examined the use of cyclodextrin-derived artificial enzymes in promoting bimolecular aldol reactions, specifically those of m-nitrobenzaldehyde (57) and ofp-t-butylbenzaldehyde (58) with acetone [141]. Here, we examined a group of mono-substituted cyclodextrins as catalysts (e.g. 59), as well as two disubstituted (3-cyclodextrins (e.g. 60) (10 catalysts in all). They all bound the aldehyde components in the cyclodextrin cavity and used amino groups of the substituents to convert the acetone into its enamine. An intracomplex reaction with 58 and hydrolysis of the enamine product then afforded hydroxyketone 61 (cf. 62). These catalysts imitate natural enzymes classified as Class I aldolases. 

Allyl and benzyl bromides react with a,/ -unsaturated nitriles in the presence of indium(i) iodide under sonication to produce the corresponding allylated and benzylated imines, involving exclusive addition of the allyl/benzyl group to the nitrile moiety (Equation (63)).273 The reaction of allylindium reagents with methyl cyanoacetates affords the corresponding allylation-enamination products (Equation (64)).27 l-Acyl-l,2-dihydropyridines are prepared by indium-mediated allylation of 1-acylpyridinium salts (Equation (65)).275 Quinoline and isoquinoline activated by... 

A. l-(Cyclooctylidenemethyl)piperidine. Cyclooctanecarboxalde-hyde (12.5 g, 0.089 mol) (Note 1) and piperidine (8.35 g, 0.098 mol) are dissolved in 115 mL of toluene and placed in a 250-mL, one-necked flask equipped with a magnetic stirring bar and Dean-Stark water separator on top of which is a condenser fitted with a nitrogen inlet tube. The reaction mixture is placed under a nitrogen atmosphere, then brought to and maintained at reflux with stirring for 6 hr, at which time the theoretical amount of water (1.75 mL) has been collected. The reaction mixture is cooled and fractionally distilled under reduced pressure (Note 2) toluene and excess piperidine are removed at 40°C (0.5 mm), and the enamine product is distilled as a colorless liquid to yield 17.30 g (0.084 mol, 93.6%) of l-(cyclooctylidenemethyl)piperidine, bp 81-83°C (0.5 mm). 

Kuehne and Foley117 have shown that nitroethene reacts exothermically with 1-N-morpholinocyclohexene in acetonitrile to give the less substituted alkylated enamine (54), whereas the cyclobutane (53) is produced in hydrocarbon solvent. This is attributed to the increased lifetime and selectivity of the intermediate zwitterion in polar solvents, which is expressed in the proton transfer, via a six-membered transition state, to the enamine product (54, Scheme 38). 

The enamine product of decarboxylation reacts with lipoamide, displacing sulfur and opening the lipoamide ring. 

In Problem 3.14.a, we saw that the reaction of an amine with a carbonyl compound in the presence of an acid catalyst can be driven toward the enamine product by removing water from the reaction mbcture as it is formed. The reverse of this reaction is an example of the acid hydrolysis of an enamine, a mechanism that is very similar to that of the orthoacetate hydrolysis shown in Example 4.18. 

For pyrrolidine N-oxides, one might a priori anticipate iminium ion formation to occur by a syn elimination process, since the N—O and adjacent Co—bonds cannot become antiperiplanar to each other. However, the N-oxide (29a) of the steroid alkaloid conanine reacts with acetic and trifluoroacetic anhydride exclusively by the anti pathway to give the exocyclic enamine (30 Scheme 6). Release of steric strain between the C-16 methylene and the ring methyl substituent is undoubtedly a major driving force in this reaction. More revealing is the reaction of N-oxide (29b), which would give the same enamine product if a syn pathway is favored. The observed formation of compounds (31) and (32) argues in favor of the anti elimination. 

Enamines can be obtained as the products of the Polonovski reaction of amine oxides and, in particular, by reaction of piperidine A -oxides with acetic anhydride. This is primarily due to the fact that when acetate is the counterion the intermediate iminium ions are labile and readily tautomerize. The formation of enamines during the Polonovski reaction is also favored by the presence of a base. In fact, enamines are often obtained in high yield from the reaction of an IV-oxide with trifluoroacetic anhydride in the presence of triethylamine or pyridine. Conversion of intermediate iminium ions, generated under modi-fred Polonovski conditions, to enamine products can also occur during hydrolytic work-up. 

The rare-earth metal-catalyzed cyclization of aminoalkenes, aminoalkynes and aminodienes generally produces exclusively the exocyclic hydroamination products. The only exception was found in the cyclization of homopropargylamines leading to the formation of the endocyclic enamine product via a 5-endo-dig hydroamination/cyclization (32) [142], most likely due to steric strain in a potential four-membered ring exocyclic hydroamination product. Interestingly, the 5-endo-dig cyclization is still preferred even in the presence of an alkene group that would lead to a 6-exo hydroamination product [142]. 

The reaction of propargyl alcohols with an amide acetal affords enamine products ... 

PROBLEM 17.12 Write the structure of the carbinolamine intermediate and the enamine product formed in the reaction of each of the following ... 

Enamines derived from cyclohexane-1,2-dione react readily with azodicarboxylic esters but the enamine products are very resistant to hydrolysis.249... 

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