Oximes Beckmann fragmentation

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... 

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). 

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 the hydroxy-oxime (119) gave the 16,17-seco-compound (120) which can be converted, by NaBH4 reduction and acid hydrolysis, into the lactone (121). The lactone (121) may also be obtained directly upon acidification of the reaction mixture from heating the hydroxy-oxime (119) with... 

Also of synthetic significance is the Beckmann fragmentation of cis- and imm>-3-ethoxy-2,2,4-trimethylcyclobutanone oxime (71) with 3-nitrobenzoyl chloride at ambient temperature, from which the bifunctional (2S,3/ )-3-ethoxy-2,4-dimethylpent-4-enenitrile (72 61 %) and (25,3S)-3-ethoxy-2,4-dimethylpent-4-enenitrile (72 64%) are generated with approximately 98 and 91% stereoselectivity, respectively.172 Another condition for such a Beckmann fragmentation is to employ trifluoroacetic anhydride in pyridine and /< r/-butyl methyl ether at temperatures between 20-50 C, which also leads to the formation of the pent-4-enenitriles.172... 

Oximes.—Reduction of the Beckmann fragmentation product (89) with LiAlH4 gave, after acidic (HCl) work-up, the hydrochloride (91) and the hemi-acetal (92) which may be derived from the imino-intermediate (90). Oxidation of the... 

Kita, Fujioka and co-workers reported that the reaction of a-alkoxycycloalkanone oxime acetates sueh as 35 with organoaluminum reagents caused Beckmann fragmentation and subsequent carbon-carbon bond formation to give different (o-eyano-a-alkyl (or alkynyl) ethers of type 36 in high yield, as illustrated in Sch. 22 [45]. 

The trimethylsilyl group can rigorously control and direct the Beckmann fragmentation leading to the regio- and stereo-specific formation of unsaturated nitriles (equations 41 to 43). Oxime acetate (57) fragments to the cij-alkenic nitrile (58) in 90% yield, whereas its epimer (59) affords the franj-alkenic nitrile (60) in 94% yield under the same conditions. Furthermore, fluoride-induced fragmentation can re-... 

The key step in Ayer s grandisol (183 Scheme 65) synthesis is the Beckmann fragmentation of oxime (181), which is prepared from eucarvone (180). Thus, nitrile (182) is readily accessible. 

Beckmann fragmentation. An oxime that is prone to undergo Beckmann fragmentation does so with incorporation of a fluorine atom at the other severed carbon atom. 

Oximes and Related Derivatives.—Beckmann fragmentation of a-hydroxy-ketoximes occurred with dichlorocarbene. For example, a chloroform-ethyl acetate solution of the 5a-hydroxy-6-oximinocholestane (134) gave the keto-nitrile (135) with acqueous NaOH in the presence of benzyltriethylammonium chloride. Improved reduction of nitrimines to nitramines with NaBH4 and acetic acid has been reported and is exemplified by the conversion of the nitrimino-cholestane (136) into the 6 8-nitramino-compound (137). ... 

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