Enantioselective Ring Construction

Sundarababu Baskaran of IIT-Madras offers (Organic Lett. 5 583, 2003) an alternative route to indolizidines. Exposure of the epoxide 7 to Lewis acid followed by reduction leads to 11 as a single diastereomer. The authors hypothesize that this rearrangement is proceeding via intermediates 8 -10. Tosylation of 11 followed by homologation leads to the Dendrobatid alkaloid 12. 

---

Enantioselective Ring Construction by Intramolecular C-H Insertion and by Cycloaddition... 

Epoxides such as 10 can be prepared in high enantiomeric purity, by, inter alia, kinetic resolution. David Hodgson of Oxford University has demonstrated (J. Am. Chem. Soc. 2004, /26,8664) that on exposure to LTMP, monosubstituted epoxides are smoothly converted into the corresponding alkoxy carbenc or alkoxy carbenoid. When an alkene is available for insertion, the cyclopropane, in this case 11, is formed with high diastereocontrol. This represents a powerful new approach to enantioselective ring construction. It is possible that in the absence of a target alkene, the intermediate alkoxy carbene could divert to intramolecular C-H insertion, which might also proceed with substantial diastereocontrol. 

Martin JD, Perez C, Ravelo JL. Enantioselective ring construction synthesis of halogenated marine natural spiro[5.5] undecane sesquiterpenes. J. Am. Chem. Soc. 1986 108(24) 7801-7811. 

---