Aldehydes oxime synthesis

Depending on the nature of the substrates, selectivity could be completely reversed between the two isomeric products. For example, switching R1 group between Buc and Ph gave high yields of the first and second product structures, respectively. The authors noted that the reaction did not proceed if the imine contained an ortho-MeO group at R2 or if the imine was replaced with an aldehyde, oxime, or hydrazone. The catalytic cycle is initiated by C-H activation of the imine, that is, the formation of a five-membered metallocycle alkyne insertion affords the intermediate drawn in Scheme 69. It is noteworthy that this is the first report of catalytic synthesis of indene derivatives via a C-H insertion mechanism (C-H activation, insertion, intramolecular addition). 

An impressive application of an aldehyde-oxime coupling was reported by Nicolaou in their studies on the total synthesis of the complex natural product diazonamide A (see Chapter 7, Section 7.4).29,30 Naito31 and Skrydstrup32 have reported impressive applications of the heteropinacol cyclisation for the stereoselective synthesis of the azepine ring of the PKC-inhibitor balanol (see Chapter 7, Section 7.4). 

Several 3/3-(aryl)-2/3-(3-substituted isoxazol-5-yl)tropanes 375 were synthesized from methyl esters 374 by reaction with the dilithium salt of the appropriate ketone or aldehyde oxime (Scheme 90) <2004JME296>. The same procedure was applied to 7-ethoxycarbonyl-2-azabicyclo[2.2.1]heptanes for the synthesis of novel epibatidine analogues, such as 376 <2004JOC5328>. The reaction of a-bromoketone oximes with isocyanides and sodium carbonate led to 5-aminoisoxazole derivatives in good yields. Probably, isocyanides are involved in a [4-1-1] cycloaddition with nitrosoalkene intermediates <1997TL8027>. 

The total synthesis of spirotryprostatin B was accomplished by K. Fuji et al using an asymmetric nitroolefination to establish the quaternary stereocenter." The conversion of the nitroolefin to the corresponding aldehyde was carried out under reductive conditions using excess titanium(lll) chloride in aqueous solution. The initially formed aldehyde oxime was hydrolyzed in situ by the excess ammonium acetate. 

Direct IV-oxidation of these heterocycles invariably fails (see Section 3.02.7.2.8), making ring synthetic methods the only viable alternative <93CHE127>. Although there has been considerable interest in the chemistry of compounds of this type, there are no new synthetic approaches of a general nature. The most common approach is to react a-oximinoketones with aldehydes and primary amines. With formaldehyde, however, the 2-unsubstituted 1-oxides rearrange to 2-imi-dazolones. Variations on this theme allow synthesis of 1-hydroxyimidazole 3-oxides. Thus, treatment of an a-dicarbonyl compound with an aldehyde and hydroxylamine, or reaction of the aldehyde oxime or aldehyde with a 1,2-dioxime are common approaches <898773 >. Similarly, a-hydroxyamino-... 

Completion of the synthesis of caerulomycin C starts with a very efficient second Negishi coupling to give 48, but then requires oxidation to an aldehyde, oxime formation, and removal of the original ortho-directing amide. The yield of 49 was unsatisfactory. 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

Also, a-halocarbonyl compounds and a-mercaptoketones react with nitriles and aldehyde oximes in the presence of an acid as catalyzed reaction for the synthesis of thiazoles. 

The use of hypervalent iodine as an inexpensive alternative to transition metal catalysts was reported in 2013. The Liu group developed an efficient and mild iodine (III)-mediated one-pot synthesis of benzisoxazoles, which they then used for the preparation of isoxazolo[5,4-iodobenzene diacetate in a 1 2 mixture of water and acetonitrile at room temperature, followed by the addition of the aldehyde oxime and two more equivalents of iodobenzene diacetate. Upon observed completion, o-phenylenediamine was added to the reaction mixture which was subsequently heated at 50 °C for Sh.The respective phenazines were obtained in moderate yield. 

Synthesis from Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoias ia a oae-pot procedure (Bucherer-Bergs reactioa) that proceeds through a complex mechanism (69). Some derivatives, like oximes, semicarbazones, thiosemicarbazones, and others, are also suitable startiag materials. The Bucherer-Bergs and Read hydantoia syntheses give epimeric products when appHed to cycloalkanones, which is of importance ia the stereoselective syathesis of amino acids (69,70). 

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)... 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

A closely related protocol for the synthesis of imidazoles was independently investigated by Sparks and Combs (Scheme 6.199) [362]. Here, the authors employed readily available unsymmetrical keto-oximes as building blocks, initially leading to N-hydroxyimidazoles. Diaryl keto-oximes were condensed with various aldehydes (1.1 equivalents) in the presence of 4 equivalents of ammonium acetate under microwave conditions at 160 °C. In this way, the N-hydroxyimidazoles were formed... 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

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