Premium
Iridium‐Catalyzed Reductive Nitro‐Mannich Cyclization
Author(s) -
Gregory Alex W.,
Chambers Alan,
Hawkins Alison,
Jakubec Pavol,
Dixon Darren J.
Publication year - 2015
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.201405256
Subject(s) - iridium , nitro , chemistry , enamine , catalysis , combinatorial chemistry , natural product , mannich reaction , organic chemistry , alkyl
A new chemoselective reductive nitro‐Mannich cyclization reaction sequence of nitroalkyl‐tethered lactams has been developed. Relying on the rapid and chemoselective iridium(I)‐catalyzed reduction of lactams to the corresponding enamine, subsequent nitro‐Mannich cyclization of tethered nitroalkyl functionality provides direct access to important alkaloid natural‐product‐like structures in yields up to 81 % and in diastereoselectivities that are typically good to excellent. An in‐depth understanding of the reaction mechanism has been gained through NMR studies and characterization of reaction intermediates. The new methodology has been applied to the total synthesis of (±)‐ epi ‐epiquinamide in four steps.