Lactams Beckmann rearrangement synthesis

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

The stereochemical use of the Beckmann rearrangement in assigning configuration to ketoximes has already been referred to, and it also has a large-scale application in the synthesis of the textile polymer Nylon-6 from cyclohexanone oxime (78) via the cyclic amide (lactam, 79) ... 

During the synthesis of ligands for the vesicular acetylcholine transporter, a octahy-droquinoline nucleus 361 was prepared via a ring-expansion rearrangement followed by a hydride reduction (equation 140). The yield was moderate but only one lactam 360 was produced by the Beckmann rearrangement. 

The asymmetric synthesis of (+)-Codeine 432 devised by White and colleagues included a Beckmann rearrangement to introduce the nitrogen atom in the carbocyclic structure (equation 182). Even though two isomeric lactams 430 and 431 were obtained as a result of the rearrangement, the preferential migration of the bridgehead carbon atom produced 430 as the predominant isomer. The synthesis of the non-natural enantiomer of Codeine was completed after oxidation, olefin formation and reduction. 

The synthesis of the benzazepinone portion of benazepril began with monobromination of 1-tetralone (35), followed by oxime formation to give 36 (Scheme 10.9). A Beckmann rearrangement mediated by polyphosphoric acid provided the ring-expanded lactam 37. Displacement of the a-bromine with potassium phthalimide installed the necessary... 

The synthesis of aza-2-cycloheptanone (e-caprolactam) by the Beckmann rearrangement of the oxime of cyclohexanone is of commercial importance because the lactam is an intermediate in the synthesis of a type of nylon (a polyamide called nylon-6 2) ... 

The Beckmann rearrangement is used in a similar way to produce the lactam 32, an intermediate in the synthesis of swainsonine 33. Stereoselective addition of dichloroketene to the enol ether 30 gave one isomer ( 95 5) of cyclobutanone 31. Beckmann rearrangement with a sulfonated hydroxylamine and dechlorination gave the lactam 32 in 34% yield over five steps7 from a precursor of 30. Note that the m-alkene 30 gives the trans cyclobutanone selectively. 

Hexahydroazocines. The synthesis of stable ketene aminal diphenylphosphates 46 was accomplished departing from the eight-membered iV-BOC or iV-COOPh protected lactams 45 via their potassium enolates (Scheme 13 <1998CC1757>). Azocane-2-one 45 was easily obtained from cycloheptanone 44 by Beckmann rearrangement of its cycloheptanone-oxime and subsequent protection of the amino moiety. 

The chemistry of such bridged naphthalenes-benzomorphans and some related compounds has been reviewed previously.<1 3) The first synthesis of a benzomorphan was achieved by Barltrop(4) however, prior to that synthesis, Schopf,(5) in his investigations of the structure of morphine, had isolated the benzomorphan, 2, from a thionyl chloride-induced, second-order Beckmann rearrangement of dihydrocodeinone oxime, 1. Reinvestigation(5a,5b) of the Beckmann rearrangement and a study of the Schmidt reaction of 6-oxomor-phinans confirmed Schopf s work and led to the isolation of the anticipated lactam (2a). 

A second partial synthesis of mexicanolide (69) from 7-deacetoxy-7-oxo-khivorin (70) has been reported (see Vol. 1, p. 183). This differed only in the method used to cleave ring B. The oxime (71) underwent a Beckmann rearrangement with thionyl chloride to give the lactam (72) which was converted into the... 

Several reagents for effecting the Beckmann rearrangement of the oxime (1) to give the lactam (2) have been evaluated with a view to the synthesis of a structural analog of the natural product, muscarine. The best results are obtained with a 10 1 mixture of methanesulfonic acid and phophorus pentoxide (equation 1). ... 

In the laboratory of J.D. White, the asymmetric total synthesis of the non-natural (+)-codelne was accomplished via intramolecular carbenoid insertion In the late stages of the total synthesis It was necessary to Install a 6-membered piperidine moiety. This transformation was accomplished utilizing a Beckmann rearrangement of the cyclopentanone oxime portion of one of the intermediates. Later the 6-membered lactam was reduced to the corresponding amine with LAH. To this end, an oxime brosylate (Bs) was prepared, which underwent a smooth Beckmann rearrangement in acetic acid to provide a 69% yield of two isomeric lactams in an 11 1 ratio in favor of the desired isomer. 

J.D. White et al. reported the total synthesis of ( )-ibogamine via the catalytic asymmetric Diels-Alder reaction of benzoquinone. The azatricyclic framework of the molecule was established by converting the bicyclic ketone to the anti oxime and then subjecting it to a Beckmann rearrangement in the presence of p-toluenesulfonyl chloride to afford the 7-membered lactam. Elaboration of this lactam into the azatricyclic core of ibogamine and later to the natural product itself was accomplished in a few additional steps. 

Table 4. Synthesis of Aminocyclopropane Lactams by the Beckmann Rearrangement of Cyclopropyl Ketone Oximes...

The synthesis of Salamandra alkaloids has been reviewed (K. Oka and S. Kara, Chem. Abs., 1979, 90, 187183 Oka, ibid., 1930, 3, 46951). The structure of cycloneosamandione has been revised to (23), with a "normal" A/B ring junction. The new formulation has been confirmed by a total synthesis, starting from oxime (24) which on Beckmann rearrangement afforded lactam (25) this was converted in four steps into... 

Suginome, H., Kaji, M., and Yamada, S., Photo Induced Molecular Transformations. 87. Regiospecihc Photo Beckmann Rearrangement of Steroidal a,P Unsaturated Ketone Oximes Synthesis of Some Steroidal Enamino Lactams, J. Chem. Soc., Perkin Trans. 1, 1988, 321 326. 

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