Enamide reactions directive group

Many of these reactions occur with formation of V-acyliminium ions 2 as intermediates (equation 1), which give the enamides after elimination of the electrofuge E+ from / -carbon atom, or the V-acylimines by removal of R4 group from nitrogen atom. In that way, the V-acyliminium ions 2 appear not only as the intermediates in acid-catalyzed conversions of enamides3 but also as direct precursors of the latter. In other words, the chemistry of enamides and their V-acylimine tautomers is closely connected with V-acyliminium chemistry, a topic which has been reviewed comprehens-ively3,5-7,27-31. 

The formation of C—N bonds is an important transformation in organic synthesis, as the amine functionality is found in numerous natural products and plays a key role in many biologically active compounds [1]. Standard catalytic methods to produce C—N bonds involve functional group manipulations, such as reductive amination of carbonyl compounds [2], addition of nucleophiles to imines [3], hydrogenation of enamides [4—8], hydroamination of olefins [9] or a C—N coupling reaction [10, 11]. Recently, the direct and selective introduction of a nitrogen atom into a C—H bond via a metal nitrene intermediate has appeared as an attractive alternative approach for the formation of C—N bonds [12-24]. 

In contrast to the alkynylation of acidic C-H bonds which can also be achieved using alkynyliodonium salts, the direct C-H functionalization of aromatic compounds or olefins has never been realized with this class of reagents so far. However, after several unsuccessful attempts using palladium or copper catalysts and alkynyliodonium salts for the alkynylation of heterocycles, Waser and Brand reported in 2009 the first efficient alkynylation of indoles using TIPS-EBX 52 and AuCl as catalyst (Scheme 18) [117]. With indole, selective C3-aIkynylation was obtained. The reaction was tolerant to many functional groups such as bromides, acids, or alcohols. The method was already used in the synthesis of starting materials for Friedel-Crafts reactions of aminocyclopropanes [118] and for hydroamidation to access indole c -enamides [119]. In 2010, Nevado and de Haro demonstrated that alkynylation was also possible using directly terminal propiolic ester derivatives and (diacetoxyiodo)benzene as co-oxidant [120]. 

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