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Iridium-catalyzed reductive nitro-Mannich cyclization.

ABSTRACT: 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.

SUBMITTER: Gregory AW

PROVIDER: S-EPMC4730865 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Iridium-catalyzed reductive nitro-Mannich cyclization.

Gregory Alex W AW Chambers Alan A Hawkins Alison A Jakubec Pavol P Dixon Darren J DJ

Chemistry (Weinheim an der Bergstrasse, Germany) 20141114 1

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 understand ...[more]

PMID: 25399919

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