Imines enamine derivatives

The reduction of imines/enamines 10j-10n/36j-36n generated from p keto esters can be regarded as an interesting method for the preparation of p amino acids. This approach has been extended to the reduction ofthe imines/enamines derived from a substituted P keto esters 37 (Scheme 4.4). In this case, the fast enamine imine equilibration 38 39 is the key point since imines 39 are chiral but racemic, so that... 

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

The Michael additions of chiral cycloalkanone imines or enamines, derived from (FV l-l-phcnyl-ethanamine or (5)-2-(methoxymethyl)pyrrolidine, are highly diastereofacially selective reactions providing excellent routes to 2-substituted cycloalkanones. This is illustrated by the addition of the enamine of (S)-2-(methoxymethyl)pyrrolidine and cyclohexanone to 2-(aryl-methylene)-l,3-propanedioates to give, after hydrolysis, the (2 5,a.S )-oxodicstcrs in 35-76% yield with d.r. (2 S,aS)/(2 S,a/ ) 94 6- > 97 3 and 80-95% ee214. 

Primary and secondary halides do not perform well, mostly because N-alkylation becomes important, particularly with enamines derived from aldehydes. An alternative method, which gives good yields of alkylation with primary and secondary halides, is alkylation of enamine salts, which are prepared by treating an imine with ethylmagnesium bromide in THF ... 

The solid-state interaction of enamines (428, 333a) with trans-l,2-diben-zoylethene (87) provides quantitative yields of the pyrrole derivatives 445 or 446 [140]. These remarkable 5-cascades consist of initial vinylogous Michael addition, enol/keto tautomerism, imine/enamine tautomerism, cyclization, and elimination, all within the crystal without melting. A waste-free extraordinary atom economy is achieved that cannot nearly be obtained in solution. The milling times are unusually long here (3 h) but it s certainly worth the effort... 

The reaction of several a-amino acid esters with 0-lactones in chloroform solution gave hydroxyamide esters (equation 50), said to be useful fungicides (74JAP(K)74127918>. Enamines derived from cyclohexanone react smoothly with 0-propiolactone to give 3-(2-cyclo-hexanonyl)propionamides in reasonable yields (equation 51). No acylation of the enamine is observed. This reaction has been used as a key step in a new synthesis of 8-aza steroids (75JOC50). Cyclohexanone imines react in the same manner, except that the expected initial product cyclizes to give bicyclic lactams and enaminones (equation 52) (80T3047). 

C(R)=NR group with a nitrilium salt RCssNR .222 The acylation of the enamine can take place by the same mechanism as alkylation, but another mechanism is also possible, if the acyl halide has an a hydrogen and if a tertiary amine is present, as it often is (it is added to neutralize the HX given off). In this mechanism, the acyl halide is dehydrohalogenated by the tertiary amine, producing a ketene (7-14) which adds to the enamine to give a cyclobutanone (5-49). This compound can be cleaved in the solution to form the same acylated imine salt (27) that would form by the more direct mechanism, or it can be isolated (in the case of enamines derived from aldehydes), or it may cleave in other ways.223... 

To suppress enamine-derived side products, we explored addition of benzotriazole (BtH) to the reaction mixture. The premise behind these experiments was the ability of BtH to form stable adducts with imines,23,24 thereby blocking tautomerization of 19 to 20 through in situ formation of the benzotriazolyl derivative 21. It was hoped that subsequent hydride displacement of the Bt moiety would afford the desired mono alkylated products 23. Indeed, analytical high-performance liquid chromatography (HPLC) revealed a remarkable improvement in terms of product purity, especially for reactions carried out at room temperature, with the desired secondary anilines 23 being essentially the only products detected. In... 

At the pH of most foods and in moist systems MA exists as the enol tautomer and an enamine derivative would be the initial product while MGA would form, more slowly, the more highly colored imine derivative. 

It is evident that loss occurs to a greater extent with the di-rather than the keto-aldehyde. This is consistent with the previously mentioned theory that the enamine derivative forms more readily than the imine. 

Mechanistically it seems that the reactions follow an enamine mechanism, in which the enamine derived from the ketone and proline reacts with the imine formed in situ from the aldehyde and p-anisidine. 

The reaction of azirines with Grignard reagents is an anomalous reaction of imines. Normally an a-hydrogen is abstracted to give the enamine anion which is unreactive toward further attack of the Grignard reagent.64 The enamine derived from a 1-azirine is a 2-azirine (146) it is an unknown and probably unstable compound (Section I,A). 

Scheme 2.1 The enamine catalytic cycle. An enamine derived from an amine- or amino acid-catalyst can react with a variety of electrophiles. The aldehyde and ketone reactants that form enamines and act as nucleophiles are often described as donors . Aldehyde and imine reactants that serve as electrophiles are described as acceptors for aldol and Mannich reactions, respectively. Ketones also serve as acceptors for aldol reactions.

Diazadienes 370 and 371, formed in situ from the corresponding silyl imine and phenylisocyanate, readily undergo [4 + 2] cycloadditions with enamines derived from butyraldehyde and cyclohexanone leading, after deamination, to pyrimidone 372 and pyrimidothione 373, respectively224. 

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