Intramolecular addition-elimination

The quinone 154, formed by oxidation of 6-fluoro-3,4-dihydroxyphe-nylacetic acid, cleanly eliminates fluoride giving the quinolactone 155, which can be interconverted with the quinomethane 156 by choice of conditions (99ABB98). The products 155 and 156 are not stable and give melanin-like polymers. 

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An aza analog of phthalazine 240 (pyrido[3,4-r/]pyridazine skeleton) was obtained via intramolecular addition-elimination reaction in azaphthalohydrazide 239 with the loss of hydrazine (Equation 56) <1997T8225>. In a similar approach also the 5,6-dihydro[l,2,3]triazolo[4,5-r/]pyridazin-4,7-dione skeleton was constructed <2002JHC889>. 

Another more efficient catalytic version of the reaction consists of the interaction of ketones with chiral amines [6] to form enolate-like intermediates that are able to react with electrophilic imines. It has been postulated that this reaction takes place via the catalytic cycle depicted in Scheme 33. The chiral amine (130) attacks the sp-hybridized carbon atom of ketene (2) to yield intermediate (131). The Mannich-like reaction between (131) and the imine (2) yields the intermediate (132), whose intramolecular addition-elimination reaction yields the (5-lactam (1) and regenerates the catalyst (130). In spite of the practical interest in this reaction, little work on its mechanism has been reported [104, 105]. Thus, Lectka et al. have performed several MM and B3LYP/6-31G calculations on structures such as (131a-c) in order to ascertain the nature of the intermediates and the origins of the stereocontrol (Scheme 33). According to their results, conformations like those depicted in Scheme 33 for intermediates (131) account for the chiral induction observed in the final cycloadducts. 

An intramolecular addition-elimination reaction of 3-chloro-2-acylindole substrate provided the central tropinone ring in a total synthesis of marine alkaloid caulersin 191 <04T2I47>. 

The insensitivity of allylic azide isomerization rates to substituent effects and solvent ionizing power, and the relatively small value of the negative volume of activation make it very unlikely that ion pair intermediates are involved in these reactions. The negative entropy and volume of activation are compatible with a concerted process involving a cyclic transition state resembling a 1,2,3-triazine. However, the known ability of alkyl and aryl azides to add to olefins - suggests the possibility of an intramolecular addition-elimination mechanism,viz. 

Since the heterocycle forming reaction in Scheme 35, and related reactions, is an intramolecular addition-elimination (i.e. 138 139), these reactions should be covered in Section 3.2.1. However, since many examples can be considered as one-pot preparations, they are covered here with appropriate cross-referencing. 

Carbanions of benzyl aryl sulfones are able to react with 2-nitrosodiphenylamines to produce 1,2-diaryIbenzimidazoles. The reaction appears to proceed via attack of these carbanions on the nitroso group followed by intramolecular addition-elimination process to give benzimidazoles (Scheme 1(X)) [83]. 

H-atom abstraction gives the 2-methylmalon-2 -yl-CoA radical, which rearranges rapidly to the succin-3-yl-CoA radical [174,191]. Both, fragmen-tation/recombination and intramolecular addition/elimination, via a cydo-... 

The synthesis of the aziridinyl-based core 87 of azinomycin A and B has been described (Scheme 17). The illustrated 6-iodo-6-deoxy-D-glucosamine derivative underwent fragmentation and ring closure to provide aziridine 85. Oxidative cleavage of 85, followed by Wadsworth-Homer elaboration and bromination, afforded 86 which underwent an intramolecular addition-elimination to generate 87.59... 

Although it is not always possible to rule out radical-anion promoted processes definitively, there are many intramolecular addition/elimination sequences involving arenes that are beyond any doubt polar in nature. The spontaneous cyclization of... 

A stmple and general synthesis of 2,2,4,5-tetrasubstituted furan-3(2//)-ones from 4-hydroxyalk-2-ynones and alkyl halides via tandem CO, addition-elimination protocol is described <96S 1431>. Palladiuni-mediated intramolecular cyclization of substituted pentynoic adds offers a new route to y-arylidenebutyrolactones <96TL1429>. The first total synthesis of (-)-goniofupyrone 39 was reported. Constmction of the dioxabicyclo[4.3.0]nonenone skeleton was achieved by tosylation of an allylic hydroxy group, followed by exposure to TBAF-HF <96TL5389>. 

The reaction of 2-polyfluoroalkylchromones (e.g., 323) with l,3,3-dimethyl-3,4-dihydroisoquinolines (e.g., 324) gave zwitterionic 6,7-dihydrobenzo[ ]quinolizinium compounds such as 326 (Scheme 70). The mechanism proposed for this transformation involves an addition-elimination displacement of the chromane heterocyclic oxygen by the enamine tautomer of the dihydroisoquinoline, followed by intramolecular cyclization of the intermediate 325 <20030L3123>. 

An example of intramolecular addition of an azo group to an alkene has been described 233 irradiation of azoalkene 280 affords an almost quantitative yield of the diazetidine 281 with no competing elimination of nitrogen. An analogous cycloaddition is thought to be implicated in the photoreaction of azobenzene with diketene.234... 

Suitably semi-protected pyranoses can react with soft carbon nucleophiles generating mixtures of alditols that can undergo elimination of water and intramolecular addition of the 8-hydroxy group to the intermediate alkenes.94,95... 

As we have seen (Section 4, p. 191) the range of effective molarities associated with ring-closure reactions is very much greater than that characteristic of intramolecular general acid-base catalysis the main classification is therefore in terms of mechanism. By far the largest section (I, Tables A-D) gives EM s for intramolecular nucleophilic reactions. These can be concerted displacements (mostly at tetrahedral carbon), stepwise displacements (mostly addition-elimination reactions at trigonal carbon), or additions, and they have been classified in terms of the nucleophilic and electrophilic centres. 

For neutral nucleophiles (e.g. amines, alcohols, water) there is much evidence that the addition-elimination mechanism depicted in equation 1 fits very well most of the intermolecular and intramolecular nucleophilic displacements involving nitro-activated aromatic substrates1. 

The stereochemistry of 338 and 339 in each case results from initial conjugate addition of MeO" at position 2 of the chromone ring. Ensuing attack of the formed enolate 342 upon PhI(OMe)2 occurs in an anti manner because of steric interaction. Sequential addition of MeO to the carbonyl group of 343 gives 344, and intramolecular reductive elimination of C6H5I then occurs with inversion of configuration, 344 345. The reaction is... 

Another interesting example of Ugi-Michael process is represented by the synthesis of pyridones 145 (Fig. 28), which originate from an intramolecular domino addition-elimination reaction of the active methylene group proceeding through intermediate 144 [120]. 

The reaction of iodo-substituted aryltriazenes 594 with /-PrMgCl LiCl afforded functionalized carbazoles 596. In this reaction, evaporation of i-Prl resulting from the 1/Mg-exchange is important before heating otherwise, unwanted cross-coupling products with i-Prl are observed. Mechanistically, this reaction could proceed with the formation of an arylmagnesium derivative 595 followed by intramolecular addition of the triazene onto nitrogen with the elimination of hydroxylamine (569) (Scheme 5.31). 

The Gould-Jacobs sequence (Scheme 4.1) commences with an addition-elimination reaction between aniline 30 and substituted ethylenemalonate derivative 31 to yield malonic ester 32. Subsequent intramolecular cychzation delivers the 4-hydroxy-3-carboalkoxy-quinolone 33. In the presence of an alkylating agent, 33 is converted to 34. Saponfication of the ester affords quinolone core 35. 

Taking advantage of a tandem sulfoxide elimination-sulfenic acid addition approach to cyclic sulfoxides <1977J(P1)1574>, the synthesis of a number of novel 1,4-oxathiane oxides 229 and 230 based on the intramolecular addition of sulfenic acids to alkenes or alkynes tethered through an ether linkage has been reported (Equation 38) <20050BC404>. 

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