Oximes aziridine synthesis

Unsaturated oximes are attractive substrates for aziridine synthesis. Treatment of oxime 77 with Red-Al yielded vinylaziridines 78, 79, and 80, in various ratios depending on the E/Z ratio of the starting oxime 77 (Scheme 2.22) [38]. This reaction should proceed through abstraction of HA, Hb, or He in the intermediate 81, followed by hydride reduction of the resulting 2H-azirines 82-84. 

Azirines have also been shown to be likely intermediates in the Campbell aziridine synthesis.62 This reaction is analogous to the Neber reaction in which the intermediate azirine is hydrolyzed to the aminoketone. Here the proposed azirine intermediate prepared from oxime (144) reacts with a Grignard reagent to give the aziridine (145). 

Nitrosyl halides add to alkenes references are scattered through the litnnture back to 1875 (ref. 194 and references cited therein). The adducts vary enormously in their stability, but when their structures allow they, like nonhalogenated nitroso compounds, isomerize to oximes or dimnize. The orientation of the reaction is consistent with an electrophilic medumism, in which the reagent is polarized as NO Hat. Bicyclic substrates and reaction media of low polarity favor syn addition, suggesting a four-center transition state (Scheme 81). Aziridine synthesis via NOCl/alkene adducts is discussed in Section 3.5.2.1. 

The synthesis of aziridines by the reduction of ketoximes with lithium aluminium hydride or sodium aluminium (dimethoxyethoxy) hydride ( Red-AI ) is possible when the oxime has a neighbouring double bond or phenyl group cyclohexanone oximes give amines under these conditions. A new simple, and rapid aziridine synthesis from cyclohexanones uses the above reducing agents on the trimethyl... 

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... 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Ethylenimines or aziridines [lb] can be considered cyclic imines and are only briefly covered in Section 5. The preparation of heterocyclic imine systems, semicarbazones, hydrazones, azines, and oximes, is omitted from this chapter. The synthesis of carbodiimides is presented in Chapter 9. 

The asymmetric synthesis of aziridines via these routes has been sparingly investigated. Aziridines bearing an A -alkoxy substituent can be resolved into nitrogen stereoisomers. Modest asymmetric induction was observed in the reaction of a chiral 0-alkyl oxime with dimethylsulfonium methylide (equation 41). The analogous reaction with diazomethane was not stereospecific. Earlier work in this area has been reviewed. 

Nitrosolysis of camphor ethyl acetal with ethanolic ethyl nitrite in sulphur dioxide yields the orthoester oxime (205) which is rapidly dehydrated by excess acetal to the orthoester nitrile which then reacts with sulphur dioxide to form the ester nitrile and diethyl sulphite.Further papers in this section include the full paper on ozonolysis of silyl ethers (Vol. 5, p. 33), another synthesis of camphor-enol trimethylsilyl ether (cf. Vol. 6, p. 41)/°° the conversion of camphor oxime with Grignard reagents into the corresponding imine with no aziridine formation/° the preparation of (206) by treating bornylene with trichloroacetyl isocyanate/ the oxidation of thiocam-phor to the 5-oxide and alkylation in the presence of thallium(i) ethoxide to a/S-unsaturated sulphoxides/ and the free-radical C-3 alkylation of camphor with alkenes. " ... 

Palacios, R Ochoa de Retana, A.M. Alonso, J.M. Regioselective synthesis of fluoroalkylated 3-aminophosphorus derivatives and aziridines from phosphorylated oximes and nucleophilic reagents. J. Org. Chem. 2006, 71, 6141. 

In connection with the synthesis of pyrrolo[l,2-a]indoles, intramolecular carbene insertion reactions have been developed. Although strictly involving interactions between two substituents, they will be considered here because of their chemical similarity. Thermal decomposition of the sodium salt of the tosylhydrazone (219) gives intramolecular cycloaddition followed by loss of nitrogen to yield the fused indole (220) (Equation (66)) <89JCS(Pi)2449>. This technique can be extended to include oxime ethers (221) in place of alkenes and thus provide formation of an aziridine (222) insertion into alkynes could not be achieved (Equation (67)) <9iJCS(Pi)i72i>. 

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