Fragmentations Beckmann

Benzofurazan, 7-chloro-4-nitro-, 6, 394 as fluorigenic agents, 6, 410, 426 Benzofurazan, 4-chloro-7-sulfo-ammonium salt properties, 6, 426 Benzofurazan, 4-nitro-synthesis, 6, 408 Benzofurazans, 6, 393-426 Beckmann fragmentation, 6, 412 biological activity, 6, 425 bond angles, 6, 396 bond lengths, 6, 396 diazo coupling, 6, 409 dipole moments, 6, 400 electrochemical reduction, 5, 73 electrophilic reactions, 6, 409-410 ESR spectroscopy, 6, 400... 

KF-alumina, allyl bromide, 80% yield. These conditions were developed because the typical strongly basic metal alkoxide-induced alkylation led to Beckmann fragmentation of the isoxazoline. 

The oxime 299 is silylated in the presence of catalytic amounts of TMSOTf 20 to 300, which affords, via the Beckmann fragmentation intermediate 301 and alkylation with allyltrimethylsilane 82, 66% of the seco nitrile 302 [101, 102] (Scheme 4.39). Tris(trimethylsilyl) ketenimine 303 reacts with aldehydes such as benzaldehyde in the presence of Bp3-OEt2, via the aldol adduct 304, to give the unsaturated nitriles 305, in 99% yield, and HMDSO 7 [103]. 

The natural antipode of corynantheine (35, 155, 20/ ) has elegantly been prepared by Autrey and Scullard (168), starting from yohimbone (305), synthesized and resolved previously by Swan (169). Yohimbone (305) was converted to 18-formylyohimbone (306) and then through 307 to oxime 308. On reaction with thionyl chloride, 308 underwent a Beckmann fragmentation to the trans-substituted indolo[2,3-a]quinolizine 310, which after desulfurization and esterification resulted in the levorotatory methyl corynantheate (304). This product... 

The reaction of compounds 465 with an excess of aryl isocyanate in acetonitrile at reflux leads to the formation of imidazooxadiazolones 466, via a Beckmann fragmentation that affords a presumed cyclic nitrone intermediate 187 (Equation 107) <1999SC3889>. 

Several pathways may be possible for the Beckmann fragmentation reaction (equations 68 and 69). Stepwise processes may occur (equation 68), but stereospecific concerted fragmentations are also common (equation 69). Stepwise processes may follow different routes, but in most cases the fragmentation may have the same intermediate as the Beckmann rearrangement the nitrilium ion. 

The Beckmann fragmentation with nitrile formation is the main side reaction and may be predominant. This side reaction is more important when R and/or R can form a relatively stable carbocation (equations 68 and 69). 

Fragmentation of the intermediate or concerted formation of nitriles from the activated oxime (Scheme 9, pathway 3) this is the Beckmann fragmentation. In some circumstances this pathway becomes dominant, particularly when there are quaternary carbons adjacent to the oxime. This transformation has found particular utility in ring-cleavage processes (sometimes called abnormal or second-order Beckmann rearrangements). 

The spirobicyclic lactam 377 possessing the common azaspirodecane unit present in several alkaloids was prepared by rearrangement of the oxime 376. Beckmann fragmentation products (olefins) are the main side products (15%) (equation 149). 

The Beckmann fragmentation may compete seriously with the Beckmann rearrangement. Both reactions may proceed via common intermediates and the observed selectivity strongly depends on the structural features of the starting compound. Reaction conditions can also have a strong influence on the success of the reaction. 

In some cases, the fragmentation product is largely predominant, or even the only product observed. The Beckmann fragmentation process will be analysed briefly in this text as it can limit the utility of the Beckmann rearrangement. 

Fragmentation occurs when the a-carbon-carbon bond breaks (Scheme 12), rather than migrates. When a stable carbocation (R ) can be formed, the Beckmann fragmentation can be the main reaction. A concerted process may occur (Scheme 12, process a), but a stepwise reaction should occur in the vast majority of cases (Scheme 12, process b). 

Although the Beckmann fragmentation may be regarded as a limitation for the application of the Beckmann rearrangement, it provides a synthetic method to produce nitrile compounds. Some examples from the recent literature are collected in the next section. 

Beckmann fragmentation is frequently applied to cyclic oximes resulting in a ring-cleavage reaction. Normally, a nitrile-alkene compound is obtained from the oxime and further transformation is usual. 

The D-ring of steroids has been cleaved frequently by a Beckmann fragmentation. Typical strategy uses enolate chemistry to introduce an oximino group at the a-carbonyl carbon. Reduction of the carbonyl (or addition of a carbanion) produces an a-hydroxy oxime which serves as good substrate for the fragmentation. Two examples of this strategy are shown in equations 213 and 214. 

As an example, this opening was applied to the synthesis of enantiopure 3-substituted cyclopentanones 506 from 2-norbornanones 505 ° (equation 220). The key step on this synthetic route was the Beckmann fragmentation of the oxime 505, promoted by TfaO/ pyridine. 

Beckmann fragmentation of polycyclic structures can be of great utility and was a key step in the two synthetic routes for the synthesis of propellane 510 (equation 224). Both fragmentation processes are oxygen assisted. 

Although rare, it is possible to trap the electrophilic intermediate of the Beckmann fragmentation. An example is the fluorinative Beckmann fragmentation discovered by Kirihara and colleagues (equation 226). 

Various reactions leading to by-products occur to all catalysts and, especially, the unsaturated nitriles formed by Beckmann fragmentation are easily polymerized. 

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