Enamine mechanism/route

In a study of organocatalytic asymmetric conjugate addition (ACA) of nitroalkenes to aldehydes, ESI-MS has been used to identify intermediates and the stereoselective step. Starting with quasi-enantiomeric reaction products, MS is used for back-reaction 0 screening and supports the enamine mechanism (over the enol route). 0... 

Many reactions have also been carried out in water. The mechanisms of the reactions of acetone and 1,3-dihydroxyacetone using zinc-proline and related catalysts have been probed kinetically.98 The former exhibits an enamine route, whereas the latter involves rate-limiting deprotonation of the -carbon and formation of an enolate. An umbelliferyl ether of dihydroxyacetone (37) has been used as a fluorogenic probe for enolization, which may prove useful in screening of aldolases in water. 

The most efficient rectal absorption enhancers, which have been studied, include surfactants, bile acids, sodium salicylate (NaSA), medium-chain glycerides (MCG), NaCIO, enamine derivatives, EDTA, and others [45 17]. Transport from the rectal epithelium primarily involves two routes, i.e., the paracellular route and the transcellular route. The paracellular transport mechanism implies that drugs diffuse through a space between epithelial cells. On the other hand, an uptake mechanism which depends on lipophilicity involves a typical transcellular transport route, and active transport for amino acids, carrier-mediated transport for (3-lactam antibiotics and dipeptides, and endocytosis are also involved in the transcellular transport system, but these transporters are unlikely to express in rectum (Figure 8.7). Table 8.3 summarizes the typical absorption enhancers in rectal routes. 

Asymmetric hydrogenation offers a useful synthetic route to chiral amines. Although the mechanism is unknown, only the (7%/V-acetyl-1 -arvlalkylamine 21 with 95% ee was obtained by the hydrogenation of a mixture of ( )- and (Z)-enamides 20a and 20b using Rh-Me-DuPHOS (XI). The A-acetvl enamines 20a,b are prepared by the reduction of oximes with Fe powder in acetic anhydride [21]. Also the acetamide 23 was obtained from 22 [22]. 

The review starts with a discussion of the mechanism of keto-enol tautomerisation and with kinetic data. Included in this section are results on stereochemical aspects of enolisation (or enolate formation) and on regioselec-tivity when two enolisation sites are in competition. The next section is devoted to thermodynamic data (keto-enol equilibrium constants and acidity constants of the two tautomeric forms) which have greatly improved in quality over the last decade. The last two sections concern two processes closely related to enolisation, namely the formation of enol ethers in alcohols and that of enamines in the presence of primary and secondary amines. Indeed, over the last fifteen years, data have shown that enol-ether formation and enamine formation are two competitive and often more favourable routes for reactions which usually occur via enol or enolate. 

Isomerisation studies indicate that the iminium ion formed initially prior to isomerisation as the amount of ( ) product increased over time. Only the (Z) isomer was observed after 10 min. Notably, nonenolisable aldehydes i.e. acrylaldehyde and cinnamaldehyde) were unreactive, indicative of an enamine-type mechanism as opposed to a typical aza-MBH route. Several procedures for the asymmetric, proline-catalysed MBH reaction between methyl vinyl ketone (MVK) and aromatic aldehydes have been developed to date. ... 

A plausible mechanism for the formations of 164,165, and 167 is shown in Scheme 22 [40]. Following the route a, an initially attempted reaction pathway, the tosylation of 52 occiu s. Subsequent nucleophiUc attack of the enamine (166) on the resultant tosylate (170) at the 3-position can afford 164 through 171 after work-up. Compoimd (165) is the product of [3,7] sigmat-ropic rearrangement of 170. 

In continuation of our efforts in the development of new synthetic routes for the synthesis of heterocyclic compounds using nanocatalysts, we have recently reported a novel synthesis of 3,4,5-trisubstituted furan-2(5H)-one derivatives by the one-pot three-component condensation of aldehydes, amines, and dimethyl acetylenedicar-boxylate (DMAD) by nsing nanoparticulate ZnO as a catalyst in Et0H H20 (1 1) at 90°C (Scheme 9.30) (Tekale et al. 2013). Almost all the employed aldehydes and amines reacted smoothly to afford excellent yields of the prodncts, irrespective of the natnre of the snbstitnent present on the aldehyde or amine. The plausible mechanism for the synthesis of furan-2(5 f)-ones using nano-ZnO is depicted in Figure 9.3. The catalyst promotes the formation of enamines (99) from amines (97) and DMAD (96). ZnO polarizes the carbonyl group of aldehydes to form a polarized adduct (100) which reacts with the enamines, followed by cyclization with the elimination of methanol molecules to afford the corresponding trisubstituted furanone derivatives (98). 

Alternatively, aliphatic alcohols may be converted directly to the respective dimethyl alkylamines by catalytic amination in the presence of dimethylamine and low-pressure hydrogen over copper catalyst. The mechanism is believed to involve catalytic dehydrogenation of the alcohol to an aldehyde, addition of DMA with concomitant water elimination to form the enamine, and then subsequent reduction to the alkyldimethylamine. This route is particularly favored with longer-chain alcohols, which are derived through hydrogenation of tallow, or palm fatty acids, or methyl esters... 

Three potential synthetic pathways starting horn an enamine intermediate for the formation of the quinoxahnes were presented (Scheme 53). The authors postulate that route a is the most likely pathway. Further studies into the mechanism of this reaction are in progress. 

Heterocyclic ketene aminals have been found to be good aza-ene compounds which can undergo hetero-ene reactions readily with activated carbonyl compounds and enones " to provide novel and efficient synthetic routes to y-lactam-fused diaza-heterocycles and fused di- and tri-heterocycles, respectively. Such aminals bearing a secondary enamine moiety have been found to undergo an efficient aza-ene reaction with 4-phenyl-l,2,4-triazoline-3,5-dione under very mild conditions. The regio- and diastero-selectivity of the ene reaction of 4-phenyl-l,2,4-triazoline-3,5-dione with chiral allylic alcohols and their derivatives have been studied, " while Singleton and Hang have proposed a new mechanism for the ene reactions of triazolinediones which involves an open biradical as the key intermediate. This biradical is assumed either to form the ene product or to form reversibly an intermediate aziridinium imide which would be a shunt off the main ene mechanistic pathway. 

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