ABSTRACT
A versatile nitro-Mannich/lactamisation cascade for the direct stereoselective synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles has been developed. A highly enantioenriched substituted 5-nitropiperidin-2-one was synthesised in a four component one-pot reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of substituted piperidines.
ABSTRACT
A highly diastereoselective bifunctional organocatalyst controlled Michael addition, a nitro-Mannich/lactamization cascade, a furan N-acyliminium cyclisation, a sequential alkyne RCM/syn-reduction and an alkene RCM has allowed a 19 step, highly stereoselective synthesis of (-)-nakadomarin A.
Subject(s)
Carbolines/chemical synthesis , Alkenes/chemistry , Alkynes/chemistry , Carbolines/chemistry , Oxidation-Reduction , StereoisomerismABSTRACT
A short and highly stereoselective synthesis of (-)-nakadomarin A has been developed using combinations of catalyst-controlled bond formations, one-pot multistep procedures, and powerful route-shortening reaction cascades. Several unprecedented chemical transformations were developed, including a highly Z-selective, eight-membered-ring-forming intramolecular Julia-Kocienski reaction, a highly diastereoselective intramolecular furan/iminium ion cyclization, and a sulfonic acid-controlled Z-selective macrocyclic ring-closing metathesis. In conjunction with a diastereoselective nitro olefin Michael addition under bifunctional organocatalysis and a nitro-Mannich/lactamization cascade, these transformations allowed the construction of this architecturally complex natural product in significant quantities in 12 steps (longest linear sequence) from commercially available starting materials.