Enantiocontrolled synthesis of 2,6-disubstituted piperidines by desymmetrization of meso-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. application to the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine.
A conceptually new approach to the enantiocontrolled synthesis of 2,6-disubstituted piperidines was achieved by desymmetrization of meso-2,6-dimethoxy-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. After protection of the piperidine nitrogen as a urethane derived from (+)- or (-)-trans-2-(alpha-cumyl)cyclohexyl (TCC), a sequential, one-pot methoxide abstraction/nucleophilic addition/methoxide abstraction/nucleophilic addition generated good yields of 2,6-disubstituted-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. This sequence proceeds by way of a highly diastereoselective methoxide abstraction (>40:1). High yielding protodemetalation and N-deprotection provided a simple and enantiocontrolled synthetic entry to a variety of 2,6-disubstituted piperidines. This new method was used for the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine.
Shu
Chutian
C
Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta, Georgia 30322, USA.
Liebeskind
Lanny S
LS
D000470:Alkaloids / Q000138:chemical synthesis*; D004095:Dihydropyridines / Q000737:chemistry*; D008982:Molybdenum / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000470:Alkaloids; D004095:Dihydropyridines; D009942:Organometallic Compounds; D010880:Piperidines; C412672:andrachcinine; C409726:dihydropinidine; D008982:Molybdenum