Lactams rearrangement

The preparative value of A-phenyl lactam rearrangement lies in the possibility of preparing middle and large benz-condensed rings in one step from readily available starting materials.14... 

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

The structural and stereochemical requisites for the base-catalysed C4, C -bis-jS-lactam to fused bis-y-lactam rearrangement have been studied and a pathway involving opening of the 2-azetidinone (see Scheme 119) has been proposed for the transformation. Acid-catalysed elimination of methanethiol to yield an azetinone intermediate (464) which, by nucleophilic addition of the eliminated agent, is converted into the isomeric thioesters (465) has been proposed to account for the formation of these bicyclic thioesters on reaction of tricyclic azetidinone (463) with trifluoroacetic acid. A new base-catalysed rearrangement of iV-substituted 4,4-dimethyl-1,2-thiazet-... 

The open-chain tautomers 24b and 25 of precursor incipient imidazolidine and perhydropyrimidine derivatives, which bear a six carbon transferable fragment, on acid-catalyzed reactions with tryptamine formed the diester 85. A similar reaction of 24a leads to quantitative formation of 86 and the reaction of 25 with tryptamine is appreciably faster than that of 24b. Sodium cyanoborohydride/acetic acid reduction of 85 was accompanied by intramolecular aminolysis to form piperidone 87. Its Bischler-Napieralski cyclization followed by borohydride reduction gave cis- and trara-isomers of indoloquinolizine ester 88, which on hydrolysis to acid and subsequent methylene lactam rearrangement gave methylene lactam 89. Its DIBAL reduction gave 18- or-deplancheine 84a (88T6187). 

Although armed with a wealth of experience in the field,68 several stereochemical problems proved unavoidable, and Rapoport finally resorted to interception of Evans route, thus doubly formalizing his synthesis. However, the construction of the key intermediate, via an effective a-methylene lactam rearrangement, is markedly different. 

Details regarding the thermal N-acy 1-lactam rearrangement (26)— (27) have appeared.A hydrazinium mesitylenesulphonate of arecoline has been prepared. ... 

Mercuric acetate Lactam rearrangement with aromatization... 

The completion of the synthesis required oxidation of the benzylic position and subsequent lactone-lactam rearrangement. This strategy has been commonly employed in the synthesis of AmaryUidaceae alkaloids and has been developed by Danishefsky in the first total synthesis of pancra-tistatin [180]. Reductive cleavage of the N—O bond in 296 with Sml and installation of the trifluoroacetamide in a one-pot procedure were foUowed by PCC oxidation of the benzylic ether to afford lactone 297. The acetonide moiety and the silyl ether were removed with BF EtjO and the resulting tiiol was treated with K COj in methanol, resulting in the aforementioned rearrangement of the lactone to the more stable lactam. 7-Deoxypancratistatin (298) was isolated in exceUent overaU yield and only 13 linear steps from iodopiperonol. 

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