Enamines tautomerism with imines

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

We shall consider the sequence as firstly imine formation (an abbreviated form of this mechanism is shown), followed by imine-enamine tautomerism. This provides a nucleophilic centre and allows a subsequent aldol-type reaction with enamine plus ketone. The pyrrole ring is produced by proton loss and a dehydration. 

C NMR data indicated the presence of a mobile formyl-enamine and enol-imine tautomeric mixture with the predominance of the former at 6-formyl-l,2,3,4,5,7,8,9-octahydro-ll//-pyrido[2,l-b]quinazolin-ll-ones (87JHC1045). 

The tertiary enamines, in contrast to the secondary derivatives, cannot exhibit enamine-imine tautomerism. As the free bases, they exist only in the vinylamino form. Their physico-chemical properties are in agreement with this structure, especially the spectral properties. The bands due to the stretching frequency of the carbon-carbon double bond in their infrared spectra1-25-27 (situated at 1630-1660 cm-1 according to the nature of the substituents) occur at somewhat lower frequencies, but their intensities are greatly increased in comparison to those of simple olefins because of conjugation with the free electron pair on the nitrogen atom. Indications of cis-trans isomerism... 

Diethoxy-2,5-dihydropyrimidine (27) has a flat ring in the crystalline solid phase, and the molecule is not involved in enamine-imine tautomerism in solution <86JOC4623>. The 4,6-diphenyl analogue (28), however, is in equilibrium with its 1,2-dihydro tautomer (29) in solution (Equation... 

The imine tautomerizes to the correspondent enamine. This tautomerization is facilitated by the conjugation of the enamine alkene with the ester. 

The Bode group disclosed NHC-catalyzed highly enantioselective annulations of a,P,P -trisubstituted enals with cyclic sulfonylimines. Mechanistically, it is proposed that the combination of enal and free NHC leads to the formation of the Breslow intermediate, which is oxidized to form the key a,p-unsaturated acyl azolium. Tautomerization between the imine and the enamine occurs readily in the presence of base, and the enamine is intercepted by the key a,p-unsaturated acyl azolium to form a hemiaminal which further engages in a Stork-Hickmott-Stille-type annulation via a tight-ion-pair/aza-Claisen type transition state. Lactam formation follows the protonation of enolate and brings about catalyst turnover to complete the catalytic cycle (Scheme 7.113). 

The proposed biosynthesis of piperazate residue of kutznerides, in analogy with monamycin and polyoxypeptin biosynthesis [213, 214], starts from the precursors glutamic acid and glutamine. The N—bond formation is achieved by the initial A-hydroxylation catalyzed by Ktzl, followed by the intramolecular displacement of the hydroxyl group by 5-amine as a nucleophile. The y,5-deidropiperazate is the common intermediate for all four piperazate moieties in kutznerides. Tautomerization of enamine to imine forms the -N unsaturated dehydropiperazate. Reduction of hydrazone leads to piperazate. The biosynthesis of y-chloro-substituted piperazate... 

A computational study unravelled two key factors that account for the efficiency of the gold(I)-catalysed hydroamination of alkynes with ammonia, using MeC=CMe as the model system (i) the excess nucleophile, NH3, which assists the proton transfer, and (ii) an unexpected [Au] migration, which allows a feasible enamine-imine tautomerization. ... 

Imines (like carbonyl compounds that form enols) are in equilibrium with their tautomeric forms, enamines (Section 17-9). If we write this form for our oxime, we arrive at an aminocarbonyl compound that is poised to undergo fast intramolecular formation of another hemiaminal. Dehydration produces a new cyclic enamine, which, upon inspection, is nothing but a hydrated pyridine. Finally, the driving force of aromaticity facilitates the rapid loss of water and generation of the pyridine product. 

Recently, the methodology was successfully employed for the enantioselective reduction of indoles 137 into indolines 138 using catalysts 113c and 118b (Scheme 15.28) [98gj. To faciUtate the enamine/imine tautomeric equiUbrium, the required Br0nsted acid was generated by a controlled hydrolysis of excess trichlorosilane with water. 

List and coworkers developed an excellent application of this method to a dynamic kinetic resolution approach (Scheme 11.12) [23]. In the presence of phosphoric acid catalyst la and 39, the reductive amination of racemic a,a-disubstituted aldehydes 46andpara-anisidine (17) proceeded through a tautomerization between enamine 48 and imine 49. The essential point of this protocol is that the hydrogenation of (R)-49 proceeded more rapidly than that of (S)-49 to give P-branched amine 47 in 87% yield with 96% ee. 

Analogous compounds with a secondary amino group (a,j8-unsaturated secondary amines) can, in principle, exist in either the form of imines (6) or the tautomeric form of enamines (7). As they practically occur and react in the former structure, it is more convenient to use the group designation imines. ... 

A mechanism has been formulated, starting with a condensation to give the imine 4, that can tautomerize to the corresponding enamine 5. The latter can be isolated in some cases, thus supporting the formulated mechanism. A cyclization and subsequent dehydration leads to the imine 6, which tautomerizes to yield the aromatic pyrrole 3 ... 

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

In 1992, Bergman et al. reported that zirconium bisamides Cp2Zr(NHR)2 catalyze the intermolecular hydroamination of alkynes with sterically hindered primary amines to give enamines or their tautomeric imines (e.g., Eq. 4.77) [126]. 

In marked contrast to the other hetero atom multiple bond functions cited in this section the >C=N- imine bond was not found to undergo hydrometalation. Imines with neighboring C-H bonds as in PhCH=NMe do react with 1 via imine/enamine tautomerism, but not by hydrozirconation [197]. 

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