RESUMO
A Cu(i)-catalysed addition and cyclisation sequence has been developed for the synthesis of (E)-alkylidene pyrrolinone derivatives. The reactions incorporate simple α-keto amides and alkynes as substrates, and employ a commercially available Cu(i) catalyst. The process tolerates good variation of both starting materials, and delivers the desired pyrrolinones in good yields, with high levels of stereocontrol.
RESUMO
Proton abstraction of N-tert-butoxycarbonyl-piperidine (N-Boc-piperidine) with sBuLi and TMEDA provides a racemic organolithium that can be resolved using a chiral ligand. The enantiomeric organolithiums can interconvert so that a dynamic resolution occurs. Two mechanisms for promoting enantioselectivity in the products are possible. Slow addition of an electrophile such as trimethylsilyl chloride allows dynamic resolution under kinetic control (DKR). This process occurs with high enantioselectivity and is successful by catalysis with substoichiometric chiral ligand (catalytic dynamic kinetic resolution). Alternatively, the two enantiomers of this organolithium can be resolved under thermodynamic control with good enantioselectivity (dynamic thermodynamic resolution, DTR). The best ligands found are based on chiral diamino-alkoxides. Using DTR, a variety of electrophiles can be used to provide an asymmetric synthesis of enantiomerically enriched 2-substituted piperidines, including (after Boc deprotection) the alkaloid (+)-beta-conhydrine. The chemistry was extended, albeit with lower yields, to the corresponding 2-substituted seven-membered azepine ring derivatives.
Assuntos
Azepinas/química , Compostos de Lítio/química , Piperidinas/química , Ciclização , Cinética , Ligantes , Modelos Moleculares , Estereoisomerismo , TermodinâmicaRESUMO
Two routes are described for the synthesis of the sawaranospirolides, stereoisomeric spirolactone ascorbigenins isolated from Chamaecyparis pisifera. Trapping of the keto enal formed by oxidation of a functionalised 2-(4-hydroxybutyl)furan affords a potential butenolide spiroacetal precursor to sawaranospirolides A and C. Alternatively, epoxidation of protected 3-(dihydropyran-2-yl)-3-arylpropanoic acids results in spirolactonisation to generate ent-sawaranospirolide C; a related acid-mediated spirocyclisation gave access to ent-sawaranospirolide D.
Assuntos
Chamaecyparis/química , Compostos de Espiro/síntese química , Ciclização , Oxirredução , EstereoisomerismoRESUMO
Dynamic thermodynamic resolution of N-Boc-2-lithiopiperidine is possible using a chiral ligand; the two enantiomers of this organolithium can be resolved with selectivities of up to 85 : 15 from a selection of 26 chiral diamino-alkoxide ligands screened.