Cyclopentanone Beckmann rearrangement

Nitrones derived from 2-azabicyclo[5.3.0]decane give quinolizidine compounds by photochemical Beckmann rearrangement which implies simultaneous ring expansion and ring contraction reactions. Intramolecular Schmidt reactions in 2(4-azidobutyl)-cyclopentanones also give quinolizidinone derivatives by ring expansion. Examples of both types of reactions are given in Sections 12.01.11.1 and 12.01.11.3, respectively. 

Derivatives of cyclopentanone oximes undergo Beckmann rearrangement to corresponding tetra- or hexahydropyridines or quinolines in the presence of Lewis acid (AICI3391.392 BF3.0Et2 or PPA ) or DIBAH (/-BujAlHl/CHiCb . ... 

A series of analogues of 2-iminopiperidine have been prepared and have been shown to be potent inhibitors of the human nitric oxide synthase isoforms °. The cyclopentanone oxime 346 was esterified with sodium hydroxide and benzenesulfonyl chloride and the subsequent Beckmann rearrangement afforded the 6-propylvalerolactam 348 as the major product and 3-propylvalerolactam 347 as a minor product (equation 133). The major product was converted into the intended 2-iminopiperidine 349. 

Another synthetic route via the Beckmann rearrangement, which is promoted by organoaluminum reagent along with alkylation, involves a new stereoselective reduction of the imino group. The starting oxime sulfonate (228) was synthesized from cyclopentanone (226) in three steps Reaction of 226 with 1-undecene in the presence of silver oxide produced the a-undecylcyclopentanone (227) which on successive treatment with hydroxylamine and methanesulfonyl chlo-ride-triethylamine gave the mesylate (228). Treatment of the oxime mesylate... 

Cyclopentanone Oxime. Violent reaction occurred on heating the oxime with 85% sulfuric acid to effect a Beckmann rearrangement.12... 

An earlier synthesis of the piperidine alkaloid anhydronupharamine by Beckmann rearrangement of a cyclopentanone derivative has now been extended to... 

Bur for hormones such as oestrone and testerone two carbon atoms need removing to make a cyclopentanone. This is accomplished using a Beckmann rearrangement. The oxine forms with the OH group trans to the more bulky... 

By treating o-chloromethylaniline hydrochloride with cu-benzyloxy-butyro- and -valeronitriles in refluxing o-dichlorobenzene in the presence of stannic chloride, Mufloz and Madroilero obtained the tricyclic compounds 124 and 202, respectively. The pyrido[2,l- )]quinazolines 289 were prepared by refluxing o-chloromethylaniline hydrochloride in dichlorobenzene with 2-chloropyridine and its tetrahydro derivative. The latter was obtained in situhy Beckmann rearrangement of cyclopentanone oxime with phosphorus pentachloride. 

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. 

Beckmann rearrangement to ethyl 5-cyano-2-oximinovalerate. Hydrogenation over Raney nickel and a basic co-catalyst and hydrolysis afforded DL-lysine monohydrochloride in 63% overall yield from cyclohexanone. A less fully studied application of the sequence to cyclopentanone affords DL-ornithine in overall yield of 21%. W. H. Hartung and F. Crossley, Org. Syn., Coll. Vol.,2.363 (1943)... 

The parent compound of this series, 2-chloro-3,4,5,6-tetrahydro-pyridine (XXXIX), was obtained as an intermediate in the Beckmann rearrangement of cyclopentanone oxime ( ). Thus, heating of cyclo-pentanone oxime with thionyl chloride affords about equal amounts of the lactam hydrochloride XL and the imidoyl chloride XXXIX ( ). 

Another prominent route to develop 1,5-difunctionlized molecular skeletons is the oxidative cleavage of cyclopentene derivatives (Scheme 2.57). In Corey s terminology of retrosynthesis this is the reconnect operation (reconnection of the two functionalities). Other reactions that faU under this heading include the Baeyer-Villiger oxidation and the Beckmann rearrangement of cyclopentanones. 

Phosphorous pentoxide effectively catalyzed the homogeneous liquid phase Beckmann rearrangement of cyclohexanone oxime 5 to lactam 6 in DMF. The catalytic activity was significantly increased by addition of trifluoromethanesulfonic acid as a co-catalyst. This protocol was fiuther extended to the rearrangement of acetone, acetophenone and cyclopentanone oxime to the corresponding amides. 

S)-Carvone (66) served as a novel source of chirality in a lengthy formal synthesis of N-acety1-L-acosamine (67) via the cyclopentanone derivative (68) and Involving a Beckmann rearrangement... 

Beckmann rearrangement of benzophenone oxime to PhC(Cl)=NPh (82%) is promoted by Ph3PCl2/Et3N in CH2CI2 at rt. Cyclopentanone and cyclohexanone oxime are converted to 8-valero- and e-caprolactam (76 and 86%) with PhsPCh in PhH at 50-60 The action of heat... 

Cyclobutane.—Further reports of grandisol (90) synthesis include Magnus s full paper (Vol. 6, p. 22) and an almost identical Japanese report of an earlier synthesis (Vol. 3, p. 25) based upon a dihydropyranone-ethylene cycloaddition.A third synthesis utilizes cyclopropanation of 4-methoxy-3,6,6-trimethylcyclohexa-2,4-dienone to yield (91) followed by rearrangement of the a-oxycyclopropylcarbinyl cation of (91) to (92). After reduction of the cyclobutanone, second-order Beckmann cleavage of the cyclopentanone oxime gave (93) from which grandisol (90) was readily obtained. 

---