Enantioselective synthesis of (−)-meroquinene through tandem Michael reaction methodology

• Published in: Tetrahedron Vol. 50; no. 8; pp. 2583 - 2590
• Main Authors: Barco, Achille, Benetti, Simonetta, Risi, Carmela De, Pollini, Gian P., Romagnoli, Romeo, Spalluto, Giampiero, Zanirato, Vinicio
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 21.02.1994; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Michael addition; Chiral auxiliary; Cyclization; Asymmetric synthesis; Nitrogen heterocycle; Aminoacid; Six membered ring; Tandem reaction; Ethylenic compound; Enantiomer(-)
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(01)86974-X

An enantioselective approach to the synthesis of non natural (−)-meroquinene 1 based on sequential inter- and intramolecular Michael reaction between (L)-menthyl N-benzyl-5-amino-2E-pentenoate 3 and 1-acetyloxy-4-methoxymethyloxy-2-nitrobutane 10b, acting as surrogate of 2-nitro-1,3-butadiene 4, is described. The heterocyclization process led to the formation of the piperidine ring system 12, obtained as an unseparable 80:20 mixture of diastereomers at the newly created chiral centres at C-3 and C-4, which became easily separable by column chromatography after transformation of the nitrogen protective benzyl group into the corresponding carbamates 14 and 15. Both compounds, after elaboration of the chain geminal to the nitro group into a vinyl appendage. underwent regio- and stereo-selective removal of the nitro group by palladium-catalyzed displacement with hydride generated by formate to give the precursor 19, easily converted by treatment with hydrochloric acid to 1, isolated as hydrochloride. Graphic