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The Brønsted Acid‐Catalyzed, Enantioselective Aza‐Diels–Alder Reaction for the Direct Synthesis of Chiral Piperidones
Author(s) -
Weilbeer Claudia,
Sickert Marcel,
Naumov Sergei,
Schneider Christoph
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604356
Subject(s) - enantioselective synthesis , alkylation , chemistry , brønsted–lowry acid–base theory , alkyl , mannich reaction , catalysis , phosphoric acid , lactam , silylation , organic chemistry , ring (chemistry) , diels–alder reaction , combinatorial chemistry
We disclose herein the first enantioselective aza‐Diels–Alder reaction of β‐alkyl‐substituted vinylketene silyl‐ O,O ‐acetals and imines furnishing a broad range of optically highly enriched 4‐alkyl‐substituted 2‐piperidones. As a catalyst for this one‐pot reaction we employed a chiral phosphoric acid which effects a vinylogous Mannich reaction directly followed by ring‐closure to the lactam. Subsequent fully diastereoselective transformations including hydrogenation, enolate alkylation, and lactam alkylation/reduction processes converted the cycloadducts into various highly substituted piperidines of great utility for the synthesis of natural products and medicinally active compounds.