Oximes tosylates

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

By similar procedures diazirines were prepared not only from simple aliphatic ketones but also from hydroxyketones and )3-aminoketones (B-67MI50800), and so were a large number of diazirines from steroidal ketones (65JA2665). Permanganate, bromine, chlorine and hypochlorite were used as oxidants. A one-step preparation of diazirines from ketones like 3-nonanone, ammonia and chlorine has been claimed in a patent (66USP3290289). 3,3-Diazirinedicarboxylic acid derivatives like (286) were obtained directly from oxime tosylates by the action of two moles of O-ethoxyamine (81AG(E)200). 

An a-amino ketone, obtained by the Neber rearrangement, can be further converted into an oxime tosylate, and then subjected to the Neber conditions a ,a -diamino ketones can be prepared by this route. 

Neber oxime tosylate-amino ketone rearrangement... 

An entirely different approach to the synthesis of 2H-azirinecarboxylic esters involves a modified Neber reaction of oxime tosylates derived from -keto esters (Scheme 15) [26]. 

A possible extension of the modified Neber reaction would be the synthesis of sulfonyl-substituted 2ff-azirines following the chemistry shown in Scheme 17 [27]. Unexpectedly, the oxime derived from -keto sulfones could not be converted into the oxime tosylate. Therefore, a different route to these requisite starting materials was designed, viz., via the corresponding sulfides 30 which were then oxidized with peracid to the sulfones 31. 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

The lipase-catalyzed resolution of (2/ , 35 )-3-methyl-3-phenyl-2-aziridine-methanol ( )-H by using the low-temperature method gave synthetically useful (2/ ,35 )-ll and its acetate (2S, iR)- a with (25 )-selectivity E = 55 at —40°C), while a similar reaction of (2/ , 3f )-3-methyl-3-phenyl-2-aziridinemethanol ( )-12 gave (25,35 )-12 and its acetate (2/ ,3/ )-12a with (2/ )-selectivity E = 73 at —20°C) (Scheme 2). Compound ( )-ll was prepared conveniently via diastereos-elective addition of MeMgBr to t-butyl 3-phenyl-2//-azirine-2-carboxylate, which was successfully prepared by the Neber reaction of oxime tosylate of t-butyl... 

N-Chlorocyclohexylideneimine is of theoretical interest, being isoelectronic with the oxime tosylate. On treatment with 1 mole of base the imine undergoes a Neber-type rearrangement to the a-amino ketone and has been shown to be an intermediate in the rearrangement of N,N-dichloroc> clohexylamine to 2-2imino-cyclohexanone. ... 

An efficient synthesis of 2Ff-azirines 6 substituted with a phosphate group is described. Its key step is an alkaloid catalyzed Neber reaction of -ketoxime tosylates 5 (equation 3) . Similarly, azirines containing an ester group in position 2 were obtained from tosy-lated oximes . A novel approach to substituted 2Ff-azirines using benzotriazole (Bt) methodology was recently presented. The reaction of benzotriazole oxime tosylates formed from the oxime 7 and TsCl with aqueous KOH yielded 2-(benzotriazol-l-yl)-2H-azirines. 

Another chiral synthesis of the azepine nucleus of Balanol (397) was developed by Wu and Jacobsen, once again converting a cyclohexanone oxime tosylates 399 to a seven-membered lactam (equation 162). The use of a mixture of oxime isomers did not cause... 

In an interesting fragmentation reaction, the hexahydroazocine (23) is formed by solvolysis of (22) in the presence of NaBHt in 94% yield (75TL2613). A related compound (24) can be prepared from 4-cycloheptenone oxime tosylate via the unsaturated lactam (25) (79JOC287). Whereas (25) adds bromine to the double bond, (24) undergoes a transannular reaction to give a 1-substituted pyrrolizidine (26). The latter type of reaction also occurs... 

Use of the Isomer mixture prevents isolation of oxime tosylate in crystalline form at the next step and leads to reduced overall yield of pure amine. 

Acetyl pyridine oxime tosylate Ethanone, l-(4-pyridinyl)-0-[(4-methylphenyl)sulfonylloxime (10) (74209-52-2)... 

Beckmann rearrangement of the oxime tosylate (190) to provide the 2-oxoperhydropyrido[l,2-n]pyrimidine (193) was reported by Grob et al.1A1... 

The three isomeric acetopyridine oxime tosylates, intermediates in an Organic Syntheses procedure wherein they are thermally rearranged, were found to have heats of decomposition around 1 kJ/g, enough to present a serious hazard if the reaction be conducted much beyond the decagram scale. Onset of decomposition is quite sudden at around 80°C. They are also marginally shock sensitive. The acetophenone homologue has a much lower heat of decomposition around 0.4 kJ/g. 

Hydrolysis of 2-unsubstituted 1-azirines is a potentially valuable method for the preparation of aminoaldehydes. The application of the Neber reaction to oxime tosylates derived from aldehydes does not give the aminoaldehydes.59 Instead, nitriles are produced by elimination. 

Lewis acid-catalysed rearrangement of the oxime tosylate 72 at 40 °C gave the oxazolo-azepinone 73 in 70% yield [01JHC89]. 

Intramolecular alkylation of oximes. Fuchs etal. reasoned that C-alkylation of oximes to give nitroso compounds should be possible when O- or N-alkylation would lead to strained imines. Thus treatment of the oxime tosylate (2) with 1 in a homogeneous reaction results in ring contraction to 3, presumably through a nitrosocyclopropane intermediate a. The reaction with bases insoluble in THF is much slower. 

S-Methyl 4-H-l,2-thiazete cations have been suggested as intermediates in the rearrangement of oxime tosylates of 2-mercaptomethylketones. ... 

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