Enamide product, formation

Chiral benzo[t/ thiepine fused to pyrrole ring 163 was obtained via a tandem dehydrogenation/intramolecular arylation <2001TL573>. Treatment of ct-hydroxylactam 160 with trifluoroacetic acid (TFA) at 25 °C gave a separable mixture of 163 and 165 in 64% and 22% yields, respectively (Scheme 18). Formation of the minor product 165 was a consequence of deprotonation of /V-acyliminium ion 161, followed by isomerization of unstable enamide 164. Formation of benzo[t/ thiepine 163 can be explained by a 71-aromatic intramolecular arylation of... 

Aza-annulation of 324, the six-membered ring analog of 296, with acryloyl chloride or ethyl acrylate led to the formation of a mixture of isomeric enamide products 325a and 326a (eq. 63).85 The corresponding crotyl derivatives (b) were also successfully employed in these aza-annulation... 

The observed stereochemistry of this reaction outcome prompted a detailed mechanistic investigation by Stahl within a stricdy intermolecular aminoacetoxyla-tion variant, as shown for one example in Eq. (4.19) [30]. This work clarified stereochemical aspects on the basis of extensive mechanistic investigation, including the induced formation of enamide product D under Wacker-type conditions, the authors concluded an overall sequence of syn-aminopalladation and antUC—0 bond formation to explain the product stereochemistry. This final result agrees well for both the intra- and the inter-molecular case. 

The transmetallation with organoboron reagent precedes the carbometallative addition of the arylrhodium intermediates 394 to the unsaturated substrate, and the intermediate alkenylrhodium species 395 then undergo hydrolysis to close the catalytic cycle with regeneration of the catalytically active species 393 and formation of the observed enamide products. An intermolecular carborhodation event was proposed to occur in a three-component coupling of arylboronic acids with disubstituted alkynes in the presence of methyl acrylate (Scheme 10.135) [113]. 

When an appropriate chiral phosphine ligand and proper reaction conditions are chosen, high enantioselectivity is achieved. If a diphosphine ligand of C2 symmetry is used, two diastereomers of the enamide coordination complex can be produced because the olefin can interact with either the re face or the si face. This interaction leads to enantiomeric phenylalanine products via diastereomeric Rh(III) complexes. The initial substrate-Rh complex formation is reversible, but interconversion of the diastereomeric olefin complexes may occur by an intramolecular mechanism involving an olefin-dissociated, oxygen-coordinated species (18h). Under ordinary conditions, this step has higher activation enthalpies than the subsequent oxidative addition of H2, which is the first... 

A tandem RCM-alkene isomerization sequence to form 5-, 6-, and 7-membered enol ethers was reported by Snapper and co-workers <02JA13390> (Scheme 36). In this process the RCM reaction is run under an atmosphere of 95 5 N2.TI2 to convert the intermediate ruthenium alkylidene into an olefin-isomerization catalyst. Note that alkene migration can convert isomeric metathesis products into the same 2,3-enol ether. A single example of the formation of a 6-membered tosyl enamide was reported in this manuscript. 

A completely different product outcome is observed with enamides derived from a-ketoesters12. Benzoylation of the product obtained by condensation of methyl pyruvate with benzyl amine led to the formation of enamide 21 (Scheme 6). Irradiation of 21 in methanol produced only a 10% yield of the expected cyclization product 22,... 

When the normal enamide photocyclization is disfavored, other reaction pathways can be observed13. For example, irradiation of enamide 27 leads to the formation of the expected cyclization product 28 (equation 8). 

Consequently, the acid-catalyzed reaction between ketones and nitriles via intermediate formation of Af-acyliminium ions and enamides provides various modes to connect the reactants as well as different ways of assembling end products, depending on the conditions and the structure of the substrate. The reaction is therefore very promising as a synthetic tool for making polyfunctional and heterocyclic compounds. 

Therefore, the formation of a dehydrolactam by irradiation of enamides under nonoxidative or unrestrictive conditions can be assumed to proceed via the route involving a 1,5-hydrogen shift of the Hb proton from the cyclic intermediate A to afford a thermally very unstable lactam 10 with a dihydrobenzene structure. This compound (10) would then undergo facile dehydrogenation even at room temperature to afford the dehydrolactam (9) as the final product, although the actual role of the oxidizing agent remains to be clarified. 

In continuation of the nauclefine synthesis, Sainsbury and Uttley (123) unsuccessfully investigated the regioselectivity of the photocyclization of the enamide 201 and the bromoenamide 203 though a regioselective formation of the nauclefine-type product (Scheme 79). 

Ketones and secondary amines furnish enamines in the presence of TiCl4 [580,581]. The preparation of a functionalized enamine shown in Eq. (251), in which the acetal moiety is retained in the product, illustrates the applicability of this reaction [582]. Enamines prepared by this method are summarized in Table 24. Application to an intramolecular reaction is also found in Table 24. If formation of the enamine is thermodynamically preferred to formation of the isomeric imine, the former becomes the product even in the reaction of a ketone, a primary amine, and TiCl4, as shown in Eq. (252) [583], in which the resulting enamine was, after acetylation, isolated as the enamide. 

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