Carbonylation enamides

Although from the synthetic viewpoint the more important reaction of enamides is the photocyclization, cleavage of the carbonyl C-nitrogen bond can also occur 219). The reaction product is an enaminoketone as shown in... 

BINAP (40a) was first reported as a ligand in an enantioselective hydrogenation in 1980 [172], and provides good selectivity for the reductions of dehydroamino acid derivatives [173], enamides, allylic alcohols and amines, and a,p-unsaturated acids [4, 9, 11, 12, 174, 175]. The fame of the ligand system really came with the reduction of carbonyl groups with ruthenium as the metal [11, 176]. The Rh-BINAP systems is best known for the enantioselective isomerizations... 

In the other approach, again harmalane (150) was treated with methyl 2-(di-ethylphosphono)acrylate (174), resulting in iminophosphonate 175. By its sodium borohydride reduction and subsequent lactonization, the amidophospho-nate 176 has been obtained, Wittig-Homer reaction of 176 with acetaldehyde followed by selective reduction of the carbonyl group of the enamide function supplied ( )-deplancheine in good yield (116). 

The reaction of but-l-en-3-yl diethyl phosphate with diethylamine produces N,N-diethylpent-3-enamide (86%), indicating that a Ji-allyl complex is involved in the carbonylation reaction. No isomerism to the a,p-unsaturated amides was observed. 

Anodic amide oxidations have also proven useful for selectively converting amides into enamides that have in turn been used to functionalize the carbon beta to nitrogen. For example, the four-electron oxidation of carbamates was used to introduce a carbonyl beta to a nitrogen (Scheme 21) [50]. In this example, the starting carbamate was oxidized at a carbon... 

In this section we consider peptide analogues containing the amide surrogates 1 to 11 (Scheme 1). These can be isosteric with the amide group in the sense that consecutive a-carbons are separated by three bonds, as in link 1, the (nitrono) peptides, and link 2, the [methyleneamino(hydroxy)] or (TV-hydroxy reduced amide) peptides. They also can be an N-modified amide, as in link 3, the (TV-hydroxy amide) peptides, and link 4, the (V-aminoamide) peptides. Elongation of the peptide unit by one covalent bond has been realized by the introduction of a heteroatom or a methylene into the backbone, as in link 5, the (hydrazide) peptides, link 6, the (amidoxy) peptides, link 7, the (oxomethyleneamino) peptides, link 8, the [(hydroxy)ethyleneamino] peptides, link 9, the (ethyleneamino) peptides, and link 10 the (oxime) peptides. Finally, insertion of an ethylenic bond (two covalent bonds) between the a-carbon and the carbonyl gives rise to link 11, the (but-2-enamide) or (vinylogous amide) peptides. 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

Condensation of an amino acid-derived anilide and a /3-ketoamide afforded l,4-benzodiazepin-2-ones in which the initially formed imine tautomerizes to an exocyclic enamide (Scheme SO) <2001TL3227>. Only the (Z)-isomer of the enamide was isolated, assigned based on NOE data, and presumably reflecting stabilization by an intramolecular H-bond between the ring NH and exocyclic amide carbonyl. 

Cyclization of alkyl radicals derived from acryl enamides gives piperidin-2-ones (Equation (10)).51 Radical carbonyla-tions have become a promising tool for the introduction of carbon monoxide into organic molecules. Macrocyclic compounds are prepared by intramolecular cyclization via radical carbonylation (Equation (1l)).53... 

An amine in the ortho position leads to the opposite regiochemical outcome in the photocyclization reaction, a consequence of a hydrogen bond between the amine and the enamide carbonyl group (equation 6)3fl. 

A case is reported164 (Scheme 115) in which a cyclic enamide was reduced at the carbonyl group by LiAlH4 as it was for lactams and amides, leaving untouched the enamine function. 

The same reaction attempted on similar non-cyclic enamides gave no results. The mechanism would involve a transition state in which Mg2 + is simultaneously linked to the NADH model and the substrate, through their respective carbonyl groups. Within this ternary complex an electron migrates from the NADH model to the substrate and this migration is successively followed by a proton transfer from the NADH model radical cation to the radical anion. 

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