1. Preparation of Substrates Epoxidation of a,b-unsaturated esters
EPOXIDATION OF UNSATURATED ESTERS. SYNTHESIS OF TRISUBSTITUTED GAMMA-BUTYROLACTONES
Santiago Rodríguez*, Florenci V. González, Javier Izquierdo, Irakusne López, Raül Portolés
Departament de Química Inorgànica i Orgànica, Universitat Jaume I, Castelló, Spain
a,b-Epoxyesters are versatile functionalities in organic synthesis since they can be converted into interesting synthetic compounds through the opening of the oxirane ring1,2. The most convenient method for their preparation is through epoxidation of unsaturated esters using a hydroperoxide in the presence of a base. A deeper understanding of the stereoselectivity of the epoxidation of unsaturated esters would increase the synthetic applications of these intermediates.
Introduction
Preparation of Substrates
The g-hydroxy-a,b-unsaturated esters 1 were obtained by treatment of ethyl (E)-4-oxo-2-butenoate with the corresponding Grignard reagent2. Ethyl (E)-4-oxo-2-butenoate was prepared from furoic acid through a three steps sequence.
Butyrolactone synthesis
Epoxide stereochemistry
Epoxidation of a,b-unsaturated esters
Reagent
Solvent
T(ºC)/t
2:3
Yield(%)
TBHP, EtLi
THF
-20/20h
70:30 60
TBHP, EtLi, TMEDA
88:12 50
THF/HMPA 42
TBHP, Et2Zn
CH2Cl2
0/120h
20:80 15
CMHP, EtLi
77:23 65
4 R= Ph
Results
•The stereoselectivity does not depend on the nature of R
group furnishing mainly syn isomer 2 (using TBPLi)
•A cation scavenger or a more polar solvent increase the
selectivity
•Zn peroxide reverses the selectivity
•Lactones are obtained under Sharpless’ conditions3 using
buffered sodium thiophenolate
•Stereochemical assignment of the lactones was performed by
NOE experiments and x-ray
References
Acknowledgments
1. Chong, J.M.; Sharpless, K.B. Tetrahedron Lett. 1985, 26,
2. Rodríguez, S.; Vidal, A.; Monroig, J.J.; González, F.V. Tetrahedron Lett. 2004, 45,
3. Behrens, C.H.; Sharpless, K.B. J.Org.Chem. 1985, 50,
This work was financed by Conselleria d’Educació, Cultura i Ciència de la Generalitat Valenciana (GV05/071) and Bancaixa-UJI foundation (P1 1A ).