A stereoselective cyclisation cascade mediated by SmI2–H2O: synthetic studies towards stolonidiol

Abstract

Dedicated to Professor Henri Kagan on the occassion of his 80th birthday a b s t r a c t A cascade reaction involving sequential conjugate reduction, stereoselective aldol cyclisation and chemoselective lactone reduction mediated by SmI 2 -H 2 O provides access to a cyclopentanol bearing two vicinal quaternary stereocentres with good stereocontrol. The functionalised cyclopentanol product has been converted to a key intermediate in ongoing asymmetric studies towards stolonidiol.

Recent Advances in the Chemistry of SmI2–H2O

“…In synthetic studies towards stolonidiol, a natural cytotoxic diterpenoid, the reagent system was used for the conversion of enantiomerically pure lactone 6 to triol 7, in a single cascade process, in good yield and high stereocontrol. [19] The cascade starts with the conjugate reduction of the electron deficient olefin and formation of a Sm(iii)-enolate which then undergoes a diastereoselective aldol cyclisation. The observed stereoselectivity can be explained by complexation of the acetate and ketone carbonyl groups with Sm(iii) in the transition state.…”

Development of an additive-controlled, SmI2-mediated stereoselective sequence: Telescoped spirocyclisation, lactone reduction and Peterson elimination

“…We first set out to examine the scope of the reductive-aldol spirocyclisation [23–27] directed by a C–Si bond, by varying the nature and functionalisation of the side chain. The ratio of 2b / 4b was optimized by adjusting the SmI 2 /MeOH ratio and the reaction time to minimise retro-aldol reaction and the formation of saturated ketolactone byproduct 4b (Table 1).…”

Approach to ferrocenyl-podophyllotoxin analogs and their evaluation as anti-tumor agents

“…Alkylation of benzydryl alcohol C and subsequent allylation of the resulting β-In light of the difficulties to allylate intermediate 4, we decided to perform the alkylation from the "pre-allylated" β-keto-ester 6[27]. Such a variant would render the synthesis more convergent with respect to the previous plan, though requiring a challenging benzhydrylation with formation of a quaternary-center.…”