Enamines and enamides

The formation of azine derivatives by condensation of enamines and enamides with 1,3-dielectrophiles has been known for almost a century, and there are a number of reactions (e.g. the Hantzsch pyridine synthesis) which proceed by intermediate formation of such compounds. Examples are shown in equations (117)—(119). The transformations outlined in equations (120) and (121) are mechanistically related processes. 

The use of enolates and ends has not been investigated in such great detail systematically, but 2-pyrones can be made by processes which, formally at least, are related to the above reactions of enamines and enamides (equations 122 and 123). In many 2-pyrone-producing reactions ambiguity exists as to the origin of the ring oxygen atom equation (122) appears... 

Fluorocylation of enamines and enamides has been intensively studied by different groups [78, 79, 80 81] The effectiveness of this particular electrophilic substitution reaction becomes obvious when the nitrogen atom ot the enamine moiety is engaged in an aromatic system [82 831 or when the olefimc system is part of an aromatic nucleus [84] (equations 37 and 38) A further extension of this reaction is demonstrated by the trifluoracetylation of aldehyde dialkyl hydrazones [85 86] (equation 39)... 

Related preparations of 2-pyridones involve condensation of enamines and enamides with 1,3-bielectrophiles, e.g., Scheme 121. 

Alkenes with Heteroatom Substituents Enamines and Enamides. The electron-donating nitrogen atom in en-amines and to a lesser extent in enamides makes for considerable reactivity... 

Enamines and enamides such as 170 mainly give the iso aldehyde, which leads to the 1,2-diamines 171 by forming and then redncing intermediate enamines [102]. 

The same catalytic system mediates also the hydroaminomethylation of olefins (Scheme 1.39) [44]. Besides piperidine, several other cyclic and linear primary and secondary amines could be utilized. Terminal and internal olefins were equally suitable for the reaction. With enamines and enamides, respectively, 1,3-diamines were formed in moderate to good yields. 

Quinolines and Related Compounds.— The Erythrina alkaloids have an interesting molecular architecture, and new routes to the skeleton and to the alkaloids themselves have been described recently. One approach requires the synthesis of the dibenzazonine system, which is now readily available by nickel-promoted coupling of a bis(iodophenyl)ethylamine (Scheme 90). An attempt to utilize an intramolecular [4 + 2] cycloaddition of enamines and enamides for the construction of the Erythrina carbon skeleton failed, but nevertheless provided an interesting synthesis of bridged bicyclotetrahydroisoquinolines (Scheme 91). ... 

With a few examples from the field of enamines and enamides, we want to close the section on nitrogen compounds. 

Enamines and enamides are valuable compounds since they are convenient precursors for a myriad of nitrogen-containing compounds. As a result, a significant number of synthetic routes are known for the preparation of these compounds. The following sections will highlight practical routes to these compounds with special attention devoted to reactions that are atom efficient, operationally simple, and have broad substrate scope. 

The copper-promoted coupling of vinylboronic acids with amines and amides bearing reactive N-H groups has been achieved (Scheme 3.118) [125]. Using the combination of copper acetate and pyridine along with air as an oxidant, a number of enamines and enamides were prepared in moderate to excellent yield. One practical advantage to this chemistry was the observation that it could be carried out in air. 

Abstract During the last decades a powerful set of protocols featuring C(sp )-N bond formation have emerged as convenient alternatives for the assembly of enamine and enamides. Those methods consist of mostly palladium-catalyzed oxidative amidations of alkenes and both palladium- and copper-catalyzed cross-couplings between generally vinyl halides or pseudohalides and amines or amides. In this review recent advances in both types of processes will be disclosed. Additionally, the synthetic value of the title processes will be illustrated by describing relevant total syntheses of natural products involving vinylation process as the key step. 

Metal-catalyzed oxidative addition of nitrogen nucleophiles such as amines and amides to olefins represents a straightforward atom economical approach for the preparation of enamines and enamides, respectively. These aminatimi processes may proceed with Markovnikov or anti-Markovnikov regioselectivity and in the latter case such products can be obtained as either or Z isomers (Scheme 1). Therefore, the ability of the catalyst to control that regiochemistry and stereoselectivity constitutes a chaUenging issue for synthetic chemists. 

Owing to the prevalence of C(sp )-N bonds as enamine and enamide moieties in numerous valuable natural products, the construction of such functionahties poses a challenging target for organic chemists and has hence stimulated the development of a vast array of methodologies. In this respect, palladium-catalyzed oxidative... 

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