- Synthesis of substituted pyrrolidines and piperidines from endocyclic enamine derivatives. Synthesis of (±)-laburnamine
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Functionalization of the α- and β-positions of readily available endocyclic enamine derivatives provides a convenient method for the formation of substituted pyrrolidines and piperidines. α-Alkoxy-β- iodopyrrolidines are formed by the electrophilic addition of iodine to the endocyclic enamine double bond of an N-substituted 2-pyrroline, and nucleophillic attack by an alcohol on the intermediate iodonium ion. The resultant α-alkoxy-β-iodopyrrolidines can be used in radical cyclization reactions to give bicyclic hemiaminal compounds, which can be further elaborated using N-acyliminium chemistry to form α,β-cis- dialkylsubstituted pyrrolidines. A strategy for the incorporation of amino functionality at the β-position was also established by using iodoamination of the enamine double bond, followed by migration of the amine functionality through an aziridination/methanolysis protocol. An alternative method uses an azidomethoxylation protocol using ceric ammonium nitrate (CAN) in the presence of NaN3 and methanol. Formation and trapping of the N-acyliminium ions derived from these substrates, afforded the 3-carbamate and 3-azido-2-substituted products with good diastereoselectivity, with the preferential formation of the trans and cis stereoisomers, respectively. Using the sequential iodoamination, aziridination in methanol and N-acyliminium transformation, trans-3-NHCO2Me-2-allyl-pyrrolidine was prepared, which was used as the key precursor in a synthesis of the natural 1-amidopyrrolizidine alkaloid, (±)-laburnamine.
- Norton Matos, Marta,Afonso, Carlos A.M.,Batey, Robert A.
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p. 1221 - 1244
(2007/10/03)
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- Synthesis of natural 1-amidopyrrolizidines, absouline and laburnamine, derivatives and aminopyrrolidinoimidazole analogues
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Natural 1-amidopyrrolizidines, absouline and laburnamine, were synthesized via stable pyrrolizidin-1-one hydrobromide. Amides, ester derivatives and aminopyrrolidinoimidazole analogues were also prepared and their biological activities tested. (C) 2000 Elsevier Science Ltd.
- Christine, C.?line,Ikhiri, Khalid,Ahond, Alain,Mourabit, Ali Al,Poupat, Christiane,Potier, Pierre
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p. 1837 - 1850
(2007/10/03)
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