Iridium-catalyzed reductive nitro-Mannich cyclization.
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.
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA (UK).
Alex W
AW
Gregory
Alan
A
Chambers
Alison
A
Hawkins
Pavol
P
Jakubec
Darren J
DJ
Dixon
D002384:Catalysis; D003500:Cyclization; D007495:Iridium / Q000737:chemistry*; D010084:Oxidation-Reduction; D011807:Quinolizines / Q000138:chemical synthesis / Q000737:chemistry; D012821:Silanes / Q000737:chemistry
D011807:Quinolizines; D012821:Silanes; C481035:epiquinamide; D007495:Iridium
Mannich reaction; amide activation; domino reactions; iridium; reduction; silanes