Cycloeliminations

Preparative routes to aziridines and 1-azirines are derived from cycloelimination processes in which one, and sometimes two, bonds are formed directly to the nitrogen atom (Scheme 1). For aziridines these include the two intramolecular cyclization pathways involving either nucleophilic displacement by the amine nitrogen (or nitrenium anion) on the /3-carbon (route a) or nucleophilic displacement by a /3-carbanionic centre on the amine nitrogen... 

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... 

More recently, several similar thermal rearrangements of other cyclic sulfoxides involving reversible intramolecular cycloelimination of sulfenic acid have also been reported . A detailed study of this rearrangement which, in certain cases, is accompanied by ring expansion or ring contraction has been performed by Jones and coworkers. These authors found that at 140 °C in xylene, conditions under which acyclic sulfoxides readily decompose , thian 1-oxide (180a) was inert after 6 days. 

The Ramberg-Backlund Reaction. a-Halosulfones undergo a related rearrangement known as the Ramberg-Backlund reaction.91 The carbanion formed by deprotonation gives an unstable thiirane dioxide that decomposes with elimination of sulfur dioxide. This elimination step is considered to be a concerted cycloelimination. 

Many other miscellaneous additions of alcohols have been described. Polar addition of methanol to 2//-pyrroles264 and to azepines265 has been observed. Photoaddition of methanol to the 1,3,4-oxadiazole 320 is followed by cycloelimination of methyl benzoate (321) to give the ylid 322.266 An adduct (323) of the ylid and the 1,3,4-oxadiazole has been isolated. Photoaddition of methanol to the quaternary ammonium salt 324 results in ring expansion and the formation of the azonine 325.267... 

Besides these cycloeliminations are also known. Many of elimination reactions proceed rapidly at room temperature but are slow at diy ice temperatures. Thus permitting carbanions containing good leaving groups to be used in substitution. 

These 6n electron additions and eliminations are apparently concerted and thus come in the category of linear cheletropic process (tt4s + co2s cycloaddition and 7t2v + o2.v + c2s cycloelimination). 

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. 

Furakawa et al. (1978) have suggested that the reaction of benzyl a-toluenethiolsulfinate shown in (71) proceeds through a mechanism (72) where there is an initial cycloelimination, followed by a recombination of PhCHjSOH and PhCH=S to give an or-sulfinylthiol, and then subsequent acylation of the thiol group. 

Aryl thiolsulfinates, ArS(0)SAr, which cannot give cycloeliminations of the type shown in (57) or (58) do, however, undergo an alternative thermal decomposition (Koch et al., 1970). Although this decomposition has sometimes been shown as having the stoichiometry of a simple disproportionation (73), somewhat more disulfide than thiolsulfonate is actually... 

The possibility of introducing a double bond into a six-membered ring may sometimes be a requirement prior to a cycloelimination process, which may also require eventually a pertinent stereochemical correction. For instance ... 

A possible synthetic pathway to seychellene (28) (Scheme 4.9) [23], for example, requires a) the substitution (FGI) of the terminal methylene group by an equivalent synlhon, such as a carbonyl group b) introduction (FGA) of a double bond in one of the cyclohexane rings and c) a retro-Diels-Alder cycloelimination (equivalent to a Diels-Alder transform) (see Heading 6.2) ... 

Besides the bond-pair cheletropic disconnection of oxiranes and aziridines to an alkene and "atomic oxygen" (from a carboxylic peracid) or a nitrene, respectively, and the hetero-Diels-Alder cycloreversion, of special interest are the 1,3-dipolar cycloeliminations of five-membered rings [-(34-2)] leading to 1,3-dipoles and an unsaturated acceptor or dipolarophile. So large is the number of different five-membered heterocyclic systems resulting from 1,3-dipolar... 

Strategies based on cycloeliminations (retro-annulations and cycloreversions) which apply mainly to fused polycyclohexane derivatives, such as steroids. 

Strategies based on very particular and specific reactions, such as Diels-Alder addition, either inter- or intramolecular (see also cycloeliminations), cationic cyclisations (important in the "biomimetic synthesis" of steroids), Pauson-... 

Remember, however that CHAOS does not intend to be a database of "synthetic methods" presently available to organic chemists. CHAOS is aimed at finding the intermediate precursors of the "synthesis tree" by means of selected basic disconnections (either "consonant" or "dissonant"). In the author s view, it is of minor importance, for instance, how a "carbene" -resulting from a -(2 + 1) cycloelimination- is generated, or whether a double bond is the direct result of a Wittig reaction or the dehydration of an alcohol formed in a Grignard reaction. In... 

The fragmentation strategy is based on a similar concept to traceless solid-phase chemistry, like retrocycloaddition cleavage, cycloelimination or cyclofragmentation. These are synthetically useful reactions with wide scope for the construction of rigid templates of different ring sizes. Up to now only one example for the attachment of heteroatoms via addition/elimination strategy has been developed, by Kurth et al. (Scheme 3.7) [188, 189]. 

Mixed ( )-cinnamyl acetals 460 undergo the enantioselective carbolithiation readily in the presence of stoichiometric or catalytic amounts, as low as 1 mol%, of (—)-sparteine (11) (equation 126) °. When quenching the reaction mixture of 461, 462 below —50°C with MeOH/HCl, the alcohols 463 are obtained with good yields and excellent ee values. However, upon warming to 20 °C, a 1,3-cycloelimination from conformation 462 gives rise to the formation of optically active trani-cyclopropanes 464 °. 

By application of the corresponding dienyl acetals 479 (n-BuLi and 0.1 equiv. of 11), enantioenriched fraw5-l-alkenyl-2-alkylcyclopropanes 481 are formed by 1,3-cycloelimination of the ally lie intermediate 480 (equation 131) . ... 

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