Synthesis Cope elimination

Table 2.1 Synthesis of secondary hydroxylamines via Cope elimination of...

The isoxazolidines (47) and (48) were obtained by cyclization of the corresponding ketone-derived exocyclic nitrones (Scheme 11).22 Such reactions have been used for natural product sysnthesis, as in the conversion of isoxazolidine (49) to ( )-hirsutene. Methylation and catalytic hydrogenolysis provided a y-dimethylamino alcohol, which underwent Cope elimination to provide an alkenyl alcohol in a key step. A related synthesis of ( )-7,12-sechoishwaran-12-ol is also reported. 

Umezawa and co-workers9 have reported a new synthesis of the tetracyclic lactam (19), which is a key intermediate in Torssell s synthesis of lycorine (cf. Vol. 9, p. 139) the Japanese work (Scheme 2), therefore, represents a formal synthesis of the alkaloid. The cyclohexyl isocyanate (15) (trans-diequatorial aryl and isocyanate groups) cyclized to a tricyclic lactam, which by reduction with a hydride and hydrolysis gave the ketone (18). The tetracyclic ketone (16) was converted into the 2,3-ene (17) by a Cope elimination reaction, and the synthesis of compound (19) was completed by transposition of the lactam carbonyl group from C-5 to C-7. 

In the first synthesis [50] phenol (150) prepared from dehydroabietic acid as starting material [51] and this was converted to trifluoroacetate (151). The azide (152) prepared from (151), underwent Curtis rearrangement yielding isocyanate (153). Reduction of (153) followed by heating the resulting material with formic acid and formaldehyde provided the tertiary amine (154). Its conversion to ketone (155) was accomplished in three steps (a) oxidation with m-cloroperbenzoic acid, (b) Cope elimination and (c) oxidative cleavage. 

In 1998, Langlois et al. completed the third synthesis of manzamine C using a strategy based on Sila-Cope elimination (Scheme 8.9) [80]. In this approach, the key intermediate, piperidine derivative 146, was prepared in six steps from 2-methylpyr-idine 143. Oxidation of 146 afforded a mixture of diastereomeric N-oxides 147 and 148. Sila-Cope elimination of N-oxide 147 led to compound 149, while Cope elimination of N-oxide 148 led to compound 150. Oxidative cleavage of the N-O bond in 149 followed by treatment with N-chlorosucdnimide provided the chlor-oamine 153. Elimination, hydrolysis, ditosylation, and finally basic treatment of the ditosylate intermediate afforded the cyclic sulfonamide 124, which is the direct synthetic precursor of manzamine C [73]. 

S.J. Danishefsky and co-workers identified an exo-methylene hydroazulenone as a versatile intermediate in efforts directed toward the total synthesis of guanacastepene. The exo-methylene group was introduced on the hydroazulene by the two-step Eschenmoser methenylation procedure. The substrate was deprotonated with LiHMDS followed by the addition of 3 equivalents of Eschenmoser s salt. The resulting a-(dimethylamino)methyl ketone was treated with mCPBA to form the A/-oxide, which spontaneously underwent a Cope elimination to afford the desired exo-methylene hydroazulenone. 

Ciganek, E. Reverse Cope elimination reactions. 2. Application to synthesis. J. Org. Chem. 1995, 60, 5803-5807. 

Sammelson, R. E., Kurth, M. J. Oxidation-Cope elimination a REM-resin cleavage protocol for the solid-phase synthesis of hydroxylamines. Tetrahedron Lett. 2001,42, 3419-3422. 

An efficient and selective procedure for the synthesis of spiro-fused isoxazolinopyrazol-3-ones 23 from 2-(spiro-isoxazolino) jS-keto esters 21, starting from methyl acrylate 14, has been developed by Kurth and co-workers (02JOC876) (Scheme 5). The process consists of utilizing the Baylis-Hillman reaction, or a quicker stepwise Michael addition, Aldol reaction and Cope elimination (MAC) procedure, 1,3-dipolar... 

More recently, Vasella and co-workers used the Cope elimination to prepare derivative 32, an important intermediate toward the synthesis of conformationally biased mimics of mannopyranosylamines.13... 

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