Cycloelimination reactions

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... 

Under the catalysis of 1 mol% of HgCl2, 4-methoxy-2-thiophenyl-2,3-allenols 365 and 367 can undergo cyclization to afford 3-phenylthiofurans 366 and 368 (Scheme 10.144) [169]. In this cycloelimination reaction, the methoxy or phenylthio substituent served as the leaving group. 

Cleavage by nucleophiles 79 Acid-catalyzed reactions with nucleophiles 81 Reactions of dialkylalkylthiosulfonium ions 83 Cycloelimination reactions of alkyl thiolsulfinates 88 Homolytic reactions of aryl thiolsulfinates 92 Oxidation of thiolsulfinates by peracids 94 Isomerizations of sulfoxides and thiolsulfinates 95... 

So far all of the mechanistic studies discussed have involved the use of thiosulfinates lacking hydrogens on both the carbon a to the sulfenyl sulfur and the carbon(s) / to the sulfinyl sulfur. There has been a good reason for this. When hydrogen atoms are present in such locations cycloelimination reactions can take place quite readily and a whole new dimension of complexity is added to the chemistry of thiolsulfinates. The details of these cycloelimination reactions and the chemistry that follows them have been brilliantly worked out in detail by Block and his co-workers (Block and O Connor, 1974a, 1973 Block and Weidman, 1973 Block, 1972a,b). We will now outline their findings. 

Three types of photoextrusion reactions have been identified in the irradiation of aryl-substituted 1,3,2-dioxathiolane 2-oxides [5 1-1-2 4-2] cycloelimination to produce a carbonyl compound, a carbene and sulfur dioxide extrusion of sulfur dioxide accompanied by a pinacol-like rearrangement to yield an aldehyde or ketone and extrusion of sulfur trioxide to give an alkene <72JOC2589>. Sensitization and quenching experiments indicate that a singlet state is responsible for the cycloelimination reaction, whereas the rearrangement and sulfur trioxide extrusion reactions arise from a triplet state <82JCR(S)175>. 

Synthesis of tetramethylallene via the cycloelimination reaction of 4-keto-3,3,5,5-tetramethylpyrazolinehydrazone using nickel peroxide at room temperature [132]. 

An unusual course of thermolysis occurs in 5-amino- and 5-alkoxytri-azolines, which are formed only as intermediates in the reaction of enamines and enol ethers with azides bearing electron-withdrawing groups it involves cleavage of the N-l/N-2 as well as the C-4/C-5 bonds of the triazoline ring to yield diazoalkanes and imines with one fewer carbon than in the triazolines (amidines and imino ethers) (Scheme 144)233.250 272 431-433 in a cycloelimination reaction, the reverse of diazoalkane-imine cycloaddition. The intermediate formation of a diazonium zwitterion is suggested,233,247 but whether the thermolysis occurs in a one- or two-step reaction is not established. 

Another significant preparative pathway to the 2i/-azirine system is the Neber rearrangement of oxime sulfonates. The presence of strong electron-withdrawing groups in the a-position to the oxime increases the acidity of those protons, and thus favors the cycloelimination reaction under mild conditions. The Neber reaction occurs either through an internal concerted nucleophilic displacement or via a vinyl nitrene (Scheme 213) <2001EJ02401>. 

Vicinal diaryloxiranes and oxiranes bearing several aryl substituents undergo (3 2+ 1) cycloelimination reactions, and are fragmented to arylcarbenes and carbonyl compounds (Eq. Carbene formation has been confirmed by... 

Much research effort has been devoted to the study of tandem hetero-IMDA-cycloelimination reactions for the synthesis of fused polycyclic aromatic heterocycles. Nitrobenzene was found to be the best solvent for the tandem IMDA reaction/cycloelimination of hydrogen cyanide from 2- 2-[(trimethylsilyl)ethynyl]phenoxy -l,3-diazine (X = O)71,72. 

Pyrimidines have been reported to undergo accelerated IMDA-cycloelimination reactions when carried out in trifluoroacetic acid as solvent104. 

Concerted Process. Thiolsulfinates are thermally labile, and those with appropriate alkyl groups are known to undergo an intramolecular cycloelimination reaction on heating (4) ... 

The following reaction sequence is suggested. Initially the thiolsul-finate undergoes an intramolecular cycloelimination reaction as in Reaction 1. Extensive supporting evidence for this postulate has been presented by Block (4) from studies on the decomposition of thiolsulfinate under mild conditions (< 100°C). Since Reaction 1 is favored over homolysis and a reactive species, thiosulfoxylic acid, is formed, Reaction 1 is probably the initial step. 

The synthetically useful / -keto y-sultones can be prepared by the cycloelimination reactions of (a-carboxyethyl) alkyl alkanesulphonates66, which in turn can be synthesized by reacting alkanesulphonyl chlorides with ethyl a-hydroxyalkyl carboxylates, as illustrated for the synthesis of 5-methyl-l,2-oxathiolan-4-one-2,2-dioxide (20) in equation 49. The ring-closure step involves the generation of a carbanion which is resonance-stabilized by the adjacent sulphonyl group (equation 50). 

The Norrish Type I reaction usually leads to decarbonylation. This is the case with dicyclopropyl ketone on irradiation at 193 nm. Decarbonylation, however, is a second step and this is preceded by ring opening of the cyclopropyl moieties to diallyl ketone. Calculations have shown that decarbonylation of cyclobutanone occurs from the nji triplet state. The resultant triplet trimethylene biradical undergoes ISC to the ground state before formation of cyclopropane. On the other hand, the cycloelimination reaction to yield ketene and ethene arises from the singlet excited state.Irradiation of cyclopentanone in aqueous and frozen aqueous solutions has been examined and the influence of applied magnetic fields assessed. Photodecarbonylation in the crystalline phase of the ketone (3) at 310 nm takes place stereospecifically with the formation of the cyclopentane derivative (4). The latter can be readily transformed into racemic herbertenolide (5). ... 

Each of the following synthetic sequences involves a Diels-Alder reaction followed by a retro Diels-Alder (cycloelimination) reaction. Provide structures for A and B, and provide a complete mechanism for each reaction sequence. 

A very different but general approach to precursors for 1,3-cycloelimination (Reaction scheme 166) implies the addition of sulfene chlorides to double bonds [477] S-Lost compounds 242 reacts with malonic ester conventionally. After transformation of the thioether 243 with dimethylsulphate into a leaving group in 244, 1,3-cyclization is possible. 

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