Amidations hydroamidation

Buchwald et al. reported a Cu(I)-catalyzed domino amidation/hydroamidation procedure of l-halobut-l-en-3-ynes 28 with ferf-butyl carbamate to form substituted W-Boc-protected pyrroles 29 (Scheme 9) [55]. 

A mechanistic study of the ruthenium-catalysed hydroamidation of terminal alkynes HC=CR with amides R CONHR, which included deuterium labelling and the in situ infrared (IR), NMR, and ESI-MS experiments, suggests that the reaction proceeds via an oxidative addition of the amide, followed by insertion of the tt-coordinated alkyne into a ruthenium-hydride bond to produce fra 5-R CON(R )-Ru(L )-CH=CHR, rearrangement to the vinylidene species... 

One of the best-characterized examples of intramolecular hydroamidation of an alkene with the tethered activated nitrogen of amide and carbamate groups is shown in Equations 16.66a and 16.66b. This reaction is catalyzed by a dicationic palladium complex ligated by a PNP pincer ligand. Like the rhodium-catalyzed hydroamination, this process occurs to form five- and six-membered rings with or without substituents to bias the system toward cyclization.. 

Nitrous oxide is reduced by CO in the presence of [Rh(C0)2C1]2 and base to N2 and C02 21 The mechanism of the reduction of aromatic nitro compounds by CO to give isocyanates has been studied by IR the catalyst is trans-PdCl2(pyridine)2.212 PeiCOg, Ru3(C0)x2 Rh6(C0)xg convert ortho-nitrostyrenes and CO into indoles in up to 75 selectivity (eq.21).213 Nil2(PPh3)2 under CO pressure catalyses the conversion of nitrobenzene and aniline to diphenylurea and CO2 the amine is used as the solvent.214 Ru3(C0)i2 catalyses the carbonylation of amines to formamides and the hydroamidation of olefins to carboxylic amides.215... 

Mechanistic studies on the Ru-catalyzed hydroamidation of terminal alkynes support the involvement of ruthenium hydride and ruthenium vinylidene species as the key intermediates [120]. The proposed pathway starts with the initial oxidative addition of the amide N-H bond to the ruthenium complex to afford ruthenium-hydride I followed by 1,2-insertion of a Jt-coordinated alkyne to vinyl-ruthenium species II. Rearrangement to the vinylidene species HI followed by nucleophilic attack of the amide and subsequent reductive elimination would give rise to the product (Scheme 20). 

As shown by reaction 5.7.1, hydroamination is the addition of an N-H bond across a C=C bond. Intramolecular hydroamination involving ring closures as illustrated by reaction 5.7.2 is also known. In recent years the addition of amides to C=C bonds has also been reported, and these are called hydroamidation reactions. 

Interestingly, a related copper catalyst system was recently utilized by Evano and co-workers for the synthesis of N,N-acetals when coupling 1,1-dibromoalkenes with certain amides [107]. Unexpectedly, this particular transformation did not proceed through two consecutive copper-catalyzed C-N bond formations and experiments conducted on ynamides under the same experimental conditions supported the plausible role of the latter species as active intermediates in the amidation process (Scheme 28). The mechanism pathway proposed by the authors consists of a first C-N cross-coupling of the alkene with the amide, followed by dehydrobromination of the coupling product and subsequent hydroamidation of the... 

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