Asymmetric synthesis of unsaturated, fused bicyclic proline analogues through amino alkylation of cyclic bis(allylsulfoximine)titanium complexes and migratory cyclization of δ-amino alkenyl aminosulfoxonium salts
In: Journal of the American Chemical Society, Jg. 125 (2003), Heft 43, S. 13243-13251
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Zugriff:
Described is an asymmetric synthesis of new Δ3a,4-unsaturated, fused bicyclic proline analogues from cyclic bis(allylsulfoximine)titanium complexes and N-tert-butylsulfonyl imino ethyl ester. Treatment of the enantiomerically pure five-, six-, seven-, and eight-membered cyclic bis(allylsulfoximine)titanium complexes with the imino ester gave mixtures of the corresponding (E,syn)- and (Z,syn)-configured, 6-sulfoximine substituted, cyclic γ,δ-unsaturated α-amino acid esters with high regio- and diastereoselectivities in good yields. Activation of the N-methyl sulfoximine group of these amino acid derivatives through methylation with Me3OBF4 afforded in nearly quantitative yields the corresponding (dimethylamino)-sulfoxonium salts. A novel migratory cyclization of these salts with DBU gave via an isomerization to the corresponding allylic (dimethylamino)sulfoxonium salts and an intramolecular substitution of the (dimethyl-amino)sulfoxonium group the enantio- and diastereomerically pure, bicyclic, N-tert-butylsulfonyl protected proline analogues having a six- and eight-membered unsaturated carbocyclic ring. Cyclization of the alkenyl (dimethylamino)sulfoxonium salts was independent of the configuration of the double bond. N,N-Dimethylphenylsulfinamide of ≥99% ee was obtained in good yield as a further reaction product. Conversion of the sulfinamide to N,S-dimethyl-S-phenylsulfoximine of ≥99% ee, the starting material for the synthesis of the allylic sulfoximines, had been accomplished previously. Finally, cleavage of the tert-butylsulfonyl protecting group with anhydrous acid furnished the fused bicyclic proline analogue containing an unsaturated six-membered ring in high yield.
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Asymmetric synthesis of unsaturated, fused bicyclic proline analogues through amino alkylation of cyclic bis(allylsulfoximine)titanium complexes and migratory cyclization of δ-amino alkenyl aminosulfoxonium salts
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Autor/in / Beteiligte Person: | KOEP, Stefan ; GAIS, Hans-Joachim ; RAABE, Gerhard |
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Zeitschrift: | Journal of the American Chemical Society, Jg. 125 (2003), Heft 43, S. 13243-13251 |
Veröffentlichung: | Washington, DC: American Chemical Society, 2003 |
Medientyp: | academicJournal |
Umfang: | print, |
ISSN: | 0002-7863 (print) |
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