Enamides stereochemistry

Stereochemistry can be interpreted in terms of conformation effects in the 1,4-biradical intermediates.199 Vinyl enol ethers and enamides add to aromatic ketones to give 3-substituted oxetanes, usually with the cis isomer preferred.200... 

The asymmetric reduction of enamides using hydrogenation conditions is a well documented reaction with a number of groups reporting excellent results [14]. Syn delivery of hydrogen from the same face of the molecule ensures that the enamide geometry defines the relative stereochemistry obtained, and a range of chiral catalysts have been developed to control the absolute stereochemistry. However, a... 

In recent years, cross-coupling methodology has emerged as a viable tool for enamide synthesis, and, indeed, there are a number of published protocols which employ palladium- or copper-catalyzed stereospecific amidations of vinyl halides [17]. For example, Buchwald and coworkers had recently shown that a copper-catalyzed cross-coupling of vinyl bromides or iodides proceeded with retention of stereochemistry (Scheme 9.16), though the only example using a tetrasubstituted vinyl halide, 23, lacked the need for any stereochemical control in the halide portion [18]. Based on this it seemed feasible that the desired enamide 22 could potentially be assembled via a comparable coupling between amide 24 and a stere-odefined vinyl halide such as 25. 

Given the disappointing result obtained with the C-4 o-anisyl derivative 134, it was evident that this method for setting up the C-3/C-4 cis stereochemistry would be very much dependent on the nature of the C-4 substituent in a manner that would not be readily predictable. A more general method for reduction of the enamides 89, 92, 94, and 96 was therefore still required. 

The first step required was the stereoselective reduction of enamide 184 to give the necessary C-3/C-4 cis stereochemistry. To enable the use of the hydroxyl group directed hydrogenation described in the section on Hydroxyl-Group-Directed Enamide Reduction, enamide 184 was... 

The stereochemistry and photocyclization of the corresponding 1 -ethyli-deneenamide 136 has also been studied (24,109). Acylation of the 1-ethyl-isoquinoline with benzoyl chloride afforded a mixture of two enamides of geometrical isomers, the unstable E (136) and stable Z isomers (137), which were easily assigned from the nuclear Overhauser effect data in their NMR spectra (24). 

The anodic dimethoxylation of simple cyclic olefins, such as cyclohexenes, results in the predominant formation of ra/w-dimethoxycyclohexanes [303,305]. However, Barba and CO workers [306] reported that the stereochemistry of l,2-dimethoxy-l,2-dihydroace-naphthene derived from acenaphthene is drastically influenced by the anode material. Palasz and Utley [307] have reported that jV-acetylpiperidines are methoxylated via the enamide intermediate species formed by the oxidation. 1,3-Dienes are also 1,4-dimethoxylated in low stereoselectivity [293]. The anodic methoxylation of or-pinene proceeds similarly to the acetoxylation, resulting in the formation of two sets of stereoisomeric products [308]. 

In the n.m.r. spectra of the macrocyclic alkaloids (10) there are a number of points of interest which depend on stereochemistry. The chemical shift of the two protons H-1 and H-2 of the enamide group is very dependent upon pH. In deuteriochloroform both are near <5 6.4, but in acetic acid H-1 appears 6.8... 

When 348 was treated with acetic anhydride in the presence of a trace of sulfuric acid, a product (C20H22N2O3) was formed. The PMR spectrum lacked both the hydroxyl absorption and the methyl singlet. The loss of 60 mass units compared to 348 indicated the enamide structure 349 as the most likely. Attempts to reduce 349 failed, but alkaline hydrolysis and diborane reduction afforded a mixture, the major component of which was identified as TV-deacetyl-20-deethylaspidospermine (350). The stereochemistry at C-21 and C-20 were not determined, but the three minor products were isomers of the major product showing a base peak in the mass spectrum at m/e 96 (351). 

The structure of the uridyl peptide antibiotics was elucidated through extensive NMR studies. These studies assigned the cis geometry of the exocyclic enamide double bond based on an NOE (nuclear Overhauser effect) signal between the vinylic proton and the methylene protons of the amino sugar [271, 272], Boojamra et al. established the absolute stereochemistry of 2,3-diaminobutyric acid as (25,35) [273], while Bugg and coworkers demonstrated the remarkable stability of the enamide present in the uridyl peptide antibiotics [274],... 

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. 

In a study of the mechanism and stereochemistry of the enamide photo-cyclization, Lenz has demonstrated that ethylidene and benzylidene isoquinoline enamides cyclize stereospecifically from the Z-isomer to yield 13-substituted oxoberberines in which the 13-substituent is quasi-axial and the C-13 and C-14 hydrogens are in a cis relationship. ... 

The rhodium-catalyzed asymmetric hydrogenation of prochiral enamides was investigated by Feldgus and Landis [691, 692]. They demonstrated that computational methods reproduce the ot-substituent effect in enamide hydrogenation catalysis and probe how the interaction of the enamide C=C bond and the catalyst varies with the structure of the substrate. The picture that emerges emphasizes the complex interaction of both electronic (i.e. those effects that do not depend on the size of the model system) and steric effects in controlling the stereochemistry of enamide hydrogenation reactions [691, 692]. 

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