Oximes and oxime ethers

Sodium cyanoborohydride is the most commonly used reagent for reduction of oximes and oxime ethers. Although this reaction is highly versatile, and does not interfere with a majority of functional groups, careful control of reaction conditions is necessary. A considerable problem in the reduction, especially for aldoximes 80 (equation 57), is the reaction of initially formed A-alkylhydroxylamine 81 with the starting oxime 80. The obtained nitrone 82 is subsequently reduced to A,A-dialkylhydroxylamine 83, which was found to be a major reaction product at pH = 4 and above. This side reaction can be avoided by adjusting the pH of the reaction mixture to 3 or below. 

Organolithium and Grignard reagents are capable of addition to the C=N bond of oximes and oxime ethers. Oxime ethers can react directly while addition to oximes requires two equivalents of an organometallic reagent. The majority of experimental... 

Free radical addition to oximes and oxime ethers emerged as a useful alternative to addition of organometallic reagents, particularly for intramolecular reactions. The most important advantage of free radical V5. organometallic addition is its tolerance for almost any functional group (with the exception of thiocarbonyl and iodoalkyl functions). 

Oximes of certain sterols were examined as inhibitors of cholesterol biosynthesis, by suppressing two enzymes that are involved in the biochemical pathway of cholesterol biosynthesis. This dual activity indicates a promising series of biologically reactive oximes (and oxime ethers) capable of reducing cholesterol levels . 

In contrast to alkylations of oximes and oxime ethers, geminal dialkylation can be achieved with the cyclic analogs15, e.g., preparation of the 4,4-dimethyl derivative 3. 

Nucleophilic Addition to Imines and Mine Derivatives 1.12.8 ORGANOMETALLIC ADDITIONS TO OXIMES AND OXIME ETHERS... 

Oximes and oxime ethers exist as a mixture of E and Z isomers with a relatively low difference of AG° and a moderate energy barrier to isomerization (<10 kcal mol-1) [28]. They show some similarities with imines and may interconvert at room temperature, spontaneously, by an acid- or base-catalyzed isomerization involving a nitronium ion, and photochemically [29,30]. Oxime ethers have been employed as amide surrogates in peptides where they display a marked Z-E isomerism which is mainly controlled by the formation of H-bonds, which stabilize a given isomer. As an example, the structure of pseudopeptide 6 was investigated by Fourier transform infrared spectroscopy (FTIR) and NMR spectroscopy which both showed that Z-6 is folded in a /Mike conformation by a strong bifurcate hydrogen bond whereas the E isomer adopts an extended conformation (Fig. 13.5) [31]. 

Yamamoto and coworkers have studied the reactions of crotyl-9-BBN (47) and achiral aldimines (Scheme 15). These reactions occur at much lower temperature than those involving crotylboronates because of the greater reactivity of (47). No clear stereochemical pattern, however, is apparent in the data. Assuming that (47) reacts preferentially as the ( )-crotyl isomer, one would expect anti dia-stereomer (93) to be the major product via transition state (95a Scheme 16) by analogy to Hoffmann s results with oximes and oxime ethers (Schemes 8 and 14). Only in entries 1, 6, 7 and 8 of Scheme 15, however, is this stereochemical result realized. Yamamoto argues that syn diastereomer (92), the major... 

Figure 11.20 Chiral ligands/reagents used for the enantioselective reduction of oximes and oxime ethers...

Isonitrile 19 was detected in ultraviolet (UV) and infrared (IR) studies at low temperatures. They speculated that azirine intermediate 21 may precede the formation of 19 and, indeed, LFP studies on 18 performed by Richard and co-workers allowed observation of an intermediate which was assigned to 21 on the basis of the similarity of its UV absorption spectra to that of the cyclohexadienone chro-mophore. The reaction was not quenchable by piperylene and is presumed to occur via the singlet manifold. The authors did not put forward a mechanism for the formation of 21, although it may be formed by initial ESIPT from the phenol to the cyano group to give tautomer 22, which can then rearrange to give 21. Similar products (substituted benzoxazoles) were observed via presumed initial ESIPT in structurally related o-hydroxy substituted aromatic oximes and oxime ethers. ... 

Haley, M. E and Yates, K., The photochemistry of carbon-nitrogen multiple bonds in aqueous solution. 2. o-Hydroxy-substituted aromatic oximes and oxime ethers, /. Org. Chem., 52, 1825, 1987. 

Oximes and Oxime Ethers Nitrones a,p Unsaturated Oximes P,y Unsaturated Oximes y,8-Unsaturated Oximes Hydrazones... 

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