Selective Reductions of Cyclic 1,3‐Diesters by Using SmI₂ and H₂O

Abstract

SmI(2)/H(2)O reduces cyclic 1,3-diesters to 3-hydroxyacids with no over reduction. Furthermore, the reagent system is selective for cyclic 1,3-diesters over acyclic 1,3-diesters, and esters. Radicals formed by one-electron reduction of the ester carbonyl group have been exploited in intramolecular additions to alkenes. The ketal unit and the reaction temperature have a marked impact on the diastereoselectivity of the cyclizations. Cyclization cascades are possible when two alkenes are present in the starting cyclic diester and lead to the formation of two rings and four stereocenters with excellent stereocontrol.

Recent Advances in the Chemistry of SmI2–H2O

“…The desymmetrisation of readily accessible cyclic 1,3-diester derivatives was achieved, affording cis-fused bicyclic hydroxy acids in good yield and with high diastereocontrol. [17,18] The use of substrates bearing different alkene substituents led to single isolated diastereoisomers in moderate to good yields (Scheme 12). [18] Differential activation of the radical acceptors was found to be crucial in order transfer from Sm(ii) to the ester carbonyl forms a pseudoaxial ketyl radicalanion stabilised by an anomeric effect.…”

Beyond Samarium Diiodide: Vistas in Reductive Chemistry Mediated by Lanthanides(II)

“…[39] Hilmersson and co-workers have pioneered the use of SmI 2 /H 2 O/amine complexes (Scheme 17). [40] The addition of Lewis bases was found to enhance the reactivity of SmI 2 by coordination to the metal center, thus increasing the redox potential of the reagent.…”

5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

“…The first step is activation of Meldrum's acid via coordination of SmI 2 to the carbonyl group, followed by electron transfer. 6 (B) Detz et al 7 have reported that dimethyl malonate 5 can be obtained from propargylic derivative 2. The authors propose that the first step of the reaction cascade is copper-mediated addition of Meldrum's acid 2 to the triple bond and sequential methanolysis of the dioxane cycle forming lactone 6, which is further cleaved with methoxide leading to compound 5.…”

“…18 examples 57-98% 1 6 Exo-trig/exo-trig radical cyclization cascade occurs, when substituent R 2 is an alkene or alkyne; such a transformation gives fused bicyclic system 12. 10 (F) Meldrum's acid can act as a carbon-based leaving group.…”