Rearrangement-Cyclization

Cyclization of the sulfoxide 1248 with TMSOTf 20/DlPEA affords a 4 1 mixture of the tetrahydroquinolines 1249 and 1250, in 97% yield, and HMDSO 7 [49]. On heating of the sulfoxide 1251 to 80 °C Brook rearrangement then Sila-Pummerer rearrangement-cyclization gives, via 1252, 17% 1253 [50] (Scheme 8.19). 

For preparation of allyl coumarins and dihydrofuranocoumarins by tandem Claisen rearrangement-cyclization the usual procedures required vigorous reaction conditions, workup procedures were tedious, and long reaction times led to low yields. The rearrangement of allyloxycoumarins 48 to dihydrofuranocoumarins 49 has been optimized in good yields in a sealed Teflon containers with BF3-ether in N-methyl-... 

Demethoxycarbonyldihydrogambirtannine (71) was synthesized several times (189-191) before its isolation as a natural product from Ochrosia lifuana Guill. as well as Ochrosia miana H.Bn. ex Guill. (65). In the last decade, ( )-71 was elegantly synthesized by Wilcock and Winterfeldt (792) from an appropriately substituted cyclohexadienyltetrahydronorharmane derivative 349 via the Cope rearrangement, cyclization, reduction, and acid-treatment sequence. 

A related amination/rearrangement/cyclization tandem sequence had been introduced by Cossy [49]. Starting from cyclic epoxyketones 224 the reaction with propargylamines 225 caused an oxirane-opening condensation process to generate the enaminoketones 226. Upon heating in toluene to reflux, aza-Claisen rearrangement delivered the intermediate allenyl imines 227, which... 

An uncatalyzed amination/aza-Claisen rearrangement/cyclization cascade described by Majumdar et al. was terminated by a final six-membered ring for-... 

Additionally, dimedone derivative 241 and propargylamine 234 could be combined to give the alkynyl vinyl amine 242. The rearrangement/cyclization cascade could be induced upon heating until reflux in chlorobenzene. The an-... 

Pyrrolo[2,l-c][l,4]benzothiazepine 297 (R=Ph) has been prepared by an intramolecular nucleophilic displacement of acetyl derivative 296 (Scheme 64 (1992H51)). The same compound and its aryl (R = Ar (1992H51)) and carboethoxy or cyano (R = C(30Et or CN (1990H1291)) analogs can also be obtained by a Pummerer rearrangement-cyclization of sulfinyl precursor 298. 

Beckmann rearrangement of ketoketoximes 288 (R,R = alkyl, aryl) with thionyl chloride unexpectedly afforded 2-aryl(or alkyl)amino-4,6-disubstituted pyrylium salts 289 (equation 124). This reaction is the first example of rearrangement/cyclization involving carbonylic oxygen as terminator. ... 

The intermediate may be trapped by other nucleophiles (different from water) and diverse products may be obtained. The interception of the intermediate may occur inter- or intra-moleculary, the latter providing a helpful tool to produce a new ring system (Scheme 9, pathway 2). These reactions are sometimes referred to, respectively, as Beckmann rearrangement-addition and Beckmann rearrangement-cyclization reactions. 

Aromatic donble bonds may also be nsed effectively to trap the electrophilic intermediate (electrophilic aromatic snbstitntion). The Beckmann rearrangement-cyclization seqnence has fonnd ntihty in the synthesis of the isoquinoline nucleus . ... 

When the oxime precursor for the Beckmann rearrangement contains one or more oxygen atoms placed in the appropriate position, a cyclization reaction may occur. One example of a Beckmann rearrangement-cyclization involving an oxygen atom as... 

R. E. Gawley, The Beckmann reactions Rearrangements, elimination-additions, fragmentations, and rearrangement-cyclizations , in Organic Reactions, Vol. 35 (Ed. A. S. Kende), Wdey-Intersdence, London, 1988, pp. 1-415. 

A similar synthesis of mechanistic interest rather than preparative value involves the thermal reaction of dimethyl 2,5-bisdiazo-3,4-diketoadipate (89, Scheme 23) with benzofuran (91)." The presumed intermediate is the pyrone cation 90 produced from the adipate 89 by the Wolff rearrangement, cyclization, and loss of nitrogen. Electrophilic substitution then affords the benzofuran 92, which can be isolated. Ring opening and cyclization of the resultant ketene 93 then affords the dibenzofuran 94 in poor (0.4%) yield. 

Thieno[2,3-c]furans have also been prepared in situ by the Pummerer-rearrangement cyclization reaction (96JOC6166). For transient generation of thieno[2,3-c]furans see also Kuroda et al. [91JCS(CC)1635]. These compounds proved to be reactive intermediates for inter- and intramolecular Diels-Alder reactions (see Section IV). 

Although all the products can be rationalized on the basis of 7-hydrogen abstraction followed by cyclization or rearrangement-cyclization of 1,4-biradical intermediates, the mechanism has been shown to involve analogous zwitterionic intermediates [299b, 301], Although they are not strictly Norrish II reactions, transformations of 98 will be considered so for the purposes of discussion since the photoproducts and the mechanisms of their formation are very similar to those expected of Norrish II processes. 

Allylic esters equilibrated under very mild conditions (2 h, 25 C) in the presence of 2-4% PdCfe catalyst. These rearrangements were not complicated by skeletal rearrangements, cyclizations or elimination,... 

Reaction of recently synthesized 1 -al kvnyl />-( trifluoromethyl )phenyl]( tetrafluoro-borato)-X3-bromanes with 2-mercapto- benzimidazole or benzothiazole in dichloro-methane at 0°C under argon resulted in a domino Michael addition-carbene rearrangement-cyclization reaction to produce directly tricyclic heterocycles in high yields (Scheme 67).103... 

The selenetanes that have been described in the literature have been constructed via three types of reactions. Selenetane derivatives are generally prepared via the [2+2] two-component syntheses (Schemes 8 and 9 Equations 3-7). The [1+3] two-component syntheses via the reaction of a selenium nucleophile with a three-carbon unit have been carried out (Scheme 6, and Equations 8-10, 12, and 13). One-component syntheses via rearrangement-cyclization have also been performed (Scheme 7). 

This rearrangement-cyclization cascade was applied to natural products synthesis. For example, DDQ oxidation of the appropriate dihydro-3 (27T)-furanone enol acetates (Table 3.5, entries 1 and 7) afforded bullatenone and the antitumor agent geiparvarin in a very rapid route (Fig. 3.1).69 70... 

Figure 3.1. Synthetic applications of the rearrangement-cyclization cascade toward natural products.

R. E. Gawley, The Beckmann Reactions Rearrangements, Elimination-Additions, Fragmentations, and Rearrangement-Cyclizations, Org. React. 1988, 35, 1-420. 

Transition metals catalyze a very wide variety of hydrocarbon reactions ranging from hydrogenation of olefins and exchange of paraffins with deuterium at lower temperatures to skeletal rearrangement, cyclization, hydrogenolysis, cracking, and carbiding under more severe conditions. Because of this flexibility in... 

Beckmann reactions (rearrangement and rearrangement-cyclization) in synthesis of N-heterocycles 880R(35)1. 

Scheme 38 Tandem [2,3]sigmatropic rearrangement/cyclization of bis-propargylic sulfoxylate...

The same authors [166] used 2-chloropyridine derivatives 415 and 416 as precursors in the synthesis of 417 and 418 (Scheme 132), respectively. Rearrangement-cyclization of 415 (n = 2) was effected with NaH in DMF at 80 °C to give 417 (n = 2) in 44% yield (no direct cyclization product was detected). Rearrangement-cyclization of 416 leads to the product 418 in 57% yield contaminated by some 419. Chloro-pyridine derivative 416, when treated with sodium hydride in THF at 55 °C, afforded mainly the respective direct cyclization product 419. Several other base-solvent combinations were also examined. Another 0-0 rearrangement has been recently recorded [167]. 

C—O bond may cleave with carbocaiion formation this can initiate rearrangements, cyclizations or elimination reactions... 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

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