Oxime ethers

A method for protecting ketones and aldehydes is the formation of oximes, but sometimes further protection of the oximes is required. For this purpose, the oximes can be protected as allyl ethers. The oxime ethers ean be eleaved with triethylammonium formate in boiling dioxane[444]. The allyl ether of oximes is eleaved under mild conditions without attaeking the aeetal group in 677. 

MILLER - SNYDER Aiyl Cyanide Synthesis Synthesis of benzonitnies from aldehydes via oxime ethers Formation of p-cyanophenol from p nrtrobenzaldoxime and p-nitiobenzonitnle (used as a sometimes recyclable chain carrier)... 

Dehydrofluormation of A/,0-bis(tnfluoromethyl)hydroxylamine with potassium fluoride gives an excellent yield of a perfluorinated oxime ether [25] with a carhon-nitrogen double bond (equation 23)... 

Compound 14 can be dismantled in a productive fashion by ret-rosynthetic cleavage of the indicated bonds (see Scheme 4). The intermolecular attack of the amino group in 15 upon the keto function in 16 would be expected to result in the formation of the desired oxime ether after loss of a water molecule. A few functional group manipulations would then complete the synthesis of intermediate 14. A valuable structural feature of 15 is the C-2 oxygen substituent. Although this oxygen atom is not expressed in the natural product, it would certainly play an important role in our... 

Jacobsen epoxidation 359 -, Katsuki epoxidation 361 -, Mukaiyama-aldol reaction 367 f. -, oxime ether reduction 363 -, Sharpless asymmetric dihydroxyla-tion 361... 

The synthesis of alkoxy amines 2 by addition of organometallic reagents to the C-N double bond of oxime ethers 1 is plagued by the propensity for proton abstraction a. to the C-N double bond, the lability of the N-O bond and the poor electrophilicity of the oxime ethers. Therefore, frequently no products, undesired products or complex mixtures are obtained. The result depends on the substrate, organometallic reagent, solvent, temperature and additives1 6. 

Acyclic Oxime Ethers 1.4.1.5.1.1. Auxiliary-Induced Diastereoselection Stereogenic Center at Carbon... 

Reaction of the enantiomerically pure alkoxyamines 3, prepared from L-ephedrine or norephedrine derivatives 1 with acetaldehyde, isobutyraldehyde or benzaldehyde using ethanol as the solvent, afford the corresponding oxime ethers 4 as mixtures of E/Z-stereoisomers11. 

Much better results are achieved in the addition of butyllithium to oxime ethers 4a, 4b and 4c activated by boron trifluoride-diethyl ether complex (BF3 OEt2) at — 78 °C (above a reaction temperature of — 30 °C complex mixtures of products are obtained) using toluene as the solvent. Furthermore, the stereoselectivity depends on the E/Z ratio of the starting oxime ethers. The reaction appears to be highly stereoselective, with the diastereoselectivity of the... 

Table 5. Addition of Organolithium Reagents R2Li to Oxime Ethers 4 and Reduction of the Resulting Alkoxyamines 5 to Amines 6"...

I.4.I.5.2. Cyclic Oxime Ethers 1.4.1.5.2.1. Substrate-Induced Diastereoselection... 

The (TMS)3Si radical addition to terminal alkenes or alkynes, followed by radical cyclization to oxime ethers, were also studied (Reaction 50). The radical reactions proceeded effectively by the use of triethylborane as a radical initiator to provide the functionalized pyrrolidines via a carbon-carbon bond-forming process. Yields of 79 and 63% are obtained for oxime ethers connected with an olefin or propargyl group, respectively. 

The radical alkylation of ketones is achieved by their conversion into the desired N-silyloxy enamines 81 (Scheme 13). The reaction of 81 with diethyl bromomalonate in the presence of EtsB (0.5 equiv) in benzene was performed in open air and stirred at room temperature for 3h. With nitro compounds it is achieved by their conversion into the desired ]V-bis(silyloxy)enamines (82) (Scheme 13). When the reaction is carried out with 82 and alkyl iodides with an electron-withdrawing substituent at the a-position, using V-70 as radical initiator (2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile)), it underwent a clean radical alkylation reaction to yield an oxime ether. Successful radical alkylation of... 

Oximes can be alkylated by alkyl halides or sulfates. N-Alkylation is a side reaction, yielding a nitrone. " The relative yield of oxime ether and nitrone depends on the nature of the reagents, including the configuration of the oxime, and on the reaction conditions. For example, anri-benzaldoximes give nitrones, while the syn isomers give oxime ethers. " ... 

Several functional groups containing carbon-nitrogen double bonds can participate in radical cyclizations. Among these are oxime ethers, imines, and hydrazones.337 Hydrazones and oximes are somewhat more reactive than imines, evidently because the adjacent substituents can stabilize the radical center at nitrogen.338 Cyclization at these functional groups leads to amino- substituted products. 

The reactivity of oxime ethers as radical acceptors is enhanced by Lewis acids, BF3 being the most effective.343... 

Addition to oxime ethers of glyoxylic acid generates A-benzyloxyamino acids. These reactions have been done in both organic solvents344 and aqueous mixtures.345 The reactions can be done with or without Bu3SnH as a chain carrier. 

Entries 20 to 23 involve additions to C=N double bonds in oxime ethers and hydrazones. These reactions result in installation of a nitrogen substituent on the newly formed rings. Entry 20 involves the addition of the triphenylstannyl radical to the terminal alkyne followed by cyclization of the resulting vinyl radical. The product can be proto-destannylated in good yield. The ring closure generates an anti relationship for the amino substituent, which is consistent with the TS shown below. 

Indium-mediated allylation reactions of a-keto imides derived from Oppolzer s sultam proceeded in aqueous THF in good yields and excellent diastereoselectivity (Eq. 11.43).74 The indium-mediated allylation of the Oppolzer camphorsultam derivatives of glyoxylic oxime ether... 

Reaction with Propargyl Halides. The indium-mediated coupling of propargyl bromide with a variety of imines and imine oxides afforded homo-propargylamine derivatives in aqueous media under mild conditions.78 Propargylation of glyoxylic oxime ether in the presence of a catalytic amount of palladium(O) complex and indium(I) iodide in aqueous media was also studied (Eq.11.47).79... 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

Finally, a rather early (but from a mechanistic viewpoint a very interesting) sequence of radical reactions has been described by Pattenden and coworkers, in which an acetylenic oxime ether 3-312 was converted into the bicyclic oxime 3-319 in 70% yield (Scheme 3.78) [126]. Hydrolysis of 3-319 led to the bicyclic enone 3-320, which in fact can also more easily be synthesized by a Robinson annulation. 

Scheme 3.78. Domino radical double ring expansion/cyclization process with oxime ethers.

Scheme 10.14. Domino radical addition-cyclization process of oxime ethers.

Domino radical transformations on solid support can also be used, as shown by Naito and coworkers [18]. Thus, immobilized oxime ether 10-55 (Wang resin) afforded the tetrahydrofuranones 10-57 after removal of the resin, when it was exposed to BEt3 in the presence of different alkyl iodides 10-56 (Scheme 10.14). 

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

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