Enamines carbon

Enamines having a hydrogen on the enamine carbon also undergo cycloaddition to give cyclobutane derivatives. The latter are less stable, so that the reaction must be carried out under milder conditions in order to obtain... 

The reaction has been applied to more complex enamines 13) and to dienamines 19). The reduction may be rationalized by initial protonation at the enamine carbon and subsequent decarboxylation of formate ion and addition of the hydride ion to the iminium cation. This mechanism has been given support by the reaction of the enamine (205) with deuterated formic acid 143) to give the corresponding amines. The formation of 206 on reaction with DCOOH clearly indicates that protonation at the enamine carbon is the initial step. 

On the other hand, intramolecular carbon—nitrogen bond formation leading to N-substituted-3-acylpyrroles 5 smoothly occurs in 79-96% yield by heating a solution of azadiene 2 having a propargyl appendage at the enamine carbon atom (R3 = CH2—-C C—R5) in toluene or ethanol/... 

Diphenylpyrrolidine (77) catalyses the enantioselective cy-chlorination of aldehydes.299 Mechanistic and computational studies suggest that - in contrast to pre- viously proposed mechanisms involving direct formation of the carbon-electrophile bond - iV-chlorination occurs first, followed by a 1,3-sigmatropic shift of chlorine to the enamine carbon. The product iminium ion is then hydrolysed in the ratedetermining step. 

The face-selectivity originating from a steric shielding is outlined to the right in Figure 2.5. The chiral substituent in e.g. the 2-position of the pyrrolidine ring shields the Re-face of the enamine carbon atom forcing an approach of the electrophile from the opposite site (Si-face approach) of the chiral substituent. 

Extensive use has been made of the enamino ester 494 it reacts with various doubly electrophilic species at the enamine -carbon, and nitrogen, to produce bicyclic products, such as 495 using propiolic acid imidazolide, Scheme 107... 

Potassium permanganate oxidizes a heterocyclic compound, acetoneberberine, containing an enamine-type subunit61 (Scheme 44). Different products were obtained, however, when the enamine / -carbon had a methyl group. 

The number of incorporated D atoms and their positions led to the conclusion that the proton of formic acid attacks the enamine / -carbon by a reversible process (which would explain incorporation of more than 1 D per molecule). Then the hydride derived from the formate becomes attached to the iminium carbon to give the saturated amine. 

The TSs ean be readily understood by viewing them via the Newman projection down the forming C-C bond. The TSs involving the awft -enamine (53a, 53b, 55a, 55b) are lower in energy than those with the 5y -enamine. The aldehyde substituent preferentially occupies the site anti to the enamine carbon. Therefore, the lowest... 

The preference for the amine-catalyzed aldol reaction to go through a TS having the features of 53a or 55a is now called the Houk-List model. This type of TS has three major characteristics (1) proton transfer from the carboxylic acid to the incipient alcohol concomitant with the formation of the C-C bond (TS D of Scheme 6.8) (2) the enamine is in the anti orientation and (3) the aldehyde substituent is anti to the enamine carbon. 

The pyrido(2,3-d)pyrimidinediones (244a, b)34 are formed from 6-amino-l,3-dimethyluracil (243)9 which contains a stable enamine moiety with a free amino group. If in (243) the condensation with vinamidinium salts (7) takes place exclusively at the amino group or at the j3-enamine carbon also may be questionable. 

The first reports of radical addition to enamines were those of the reaction of perhaloalkanes with enamines. Carbon tetrachloride was reported to undergo photochemical and thermal reactions with enamines giving a-dichloromethylene ketones or aldehydes but no precise mechanism was proposed. Cantacuzene and Wakselman found that pyrrolidine enamines react readily with perhaloalkanes such as or... 

The nucleophilic reactivity of 17 can be increased by N-deprotonation and the best results were obtained with the in situ generated lithium salts. The latter react with acrylates by Michael addition and ring closure to give a single product. The problem of regioselectivity arises because the enamine anion 47 is delocalized and can react both at the nitrogen anion and/or at the enamine carbon. Both cases are known in the literature with similar substrates (ref. 49). These two pathways should lead to the isomeric dihydro a- or y-pyridones (Scheme 53). 

These enzymes catalyze preequilibrium proton exchange at the nucleophilic carbon center at a rate consistent with the intermediate involvement of the conjugate base in the condensation reaction (6). The reaction is formally electrophilic substitution of a carbonyl carbon for a proton at the a-carbon atom of the enamine. Stereochemical studies have shown that the proton and carbonyl bind to the same face of the enamine carbon (carbanionic center) (Scheme 7) (7). 

The reaction of 3-imino-N,l,3-triphenylprop-l-enamine (14) with dimethyl acetylenedicarboxylate (DMAD) gives the pyridone (15). If the enamine is /8-disubstituted, as in compound (16), then initial attack occurs on the imine nitrogen rather than the enamine carbon. Electrocyclization followed by loss of aniline then yields the pyridine (17) (Scheme 8). ... 

The second exanple is a new synthetic approach to the synthesis of nakadomarin A 202 rscheme 20.. 38T To this end, Wnkler and coworkers developed a tandem Pummerer-Michael process.The generation of the activated thionium ion was performed by the elimination of ethanethiol from thioacetal 198. The intermediate 199 showed double reactivity, that is, a nucleophilic position on the furan to perform the Michael addition and the usual electrophilic thionium, which was in fact trapped by the enamine carbon generating tetracyclic product 200. Winkler presented the s)mthesis of a tetracyclic model system and suggested that this reaction sequence can also be applied to the synthesis of the natural product. 

The preparation of seven-membered heterocycles was accomplished by starting from azadienes 2 with no substituents at both and C -enamine carbon atoms (R = = H) (Scheme 29). Sequential treatment of those... 

The dienamines derived from enals undergo hydroboration with 9-BBN, with high regio- and chemoselectivity at the enamine carbon-carbon double bond and place the boron atom on a carbon having higher electron density. The high selectivity is confirmed by the hydroboration of a 1 1 mixture of 1-hexene and 1-morpholino-l-octene with 1 equiv of 9-BBN. The reaction mixture affords, after the addition of methanol, a 1 1 mixture of 1-hexene and 1-octene, and no 1-hexanol is detected. Consequently, this process is used to convert unsaturated aldehydes to dienes. Thus, enamine of citronellal on hydroboration-elimination affords a chiral non-conjugated diene, p-citronellene (Scheme 24.5) [1]. 

Section 17-9 showed that the reaction of secondary amines such as azacyclopentane (pyrrolidine) with aldehydes or ketones produces enamines. As the following resonance forms indicate, the nitrogen substituent renders the enamine carbon-carbon donble bond electron rich. Furthermore, the dipolar resonance contribution gives rise to significant nucleophilicity at the remote carbon, even though the enamine is neutral. As a result, electrophiles may attack at this position. Let us see how this attack may be used to synthesize alkylated aldehydes and ketones. 

In the reaction pathway, the imininm ion formed from corresponding a,P-unsaturated aldehyde with the chiral amine is subject to nucleophilic attack by the peroxide, leading to an enamine intermediate (Schane 1.64). Formation of the epoxide then takes place by attack of the nucleophilic enamine carbon atom on the electrophilic peroxygen atom. 

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