General [4 + 1] Cyclization Approach To Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides (original) (raw)

Synthesis of Functionalized 2-Alkylidene-tetrahydrofurans Based on a [3 + 2] Cyclization/Bromination/Palladium(0) Cross-Coupling Strategy

ChemInform, 2006

The Lewis acid mediated cyclization of epoxides with 1,3-bis(trimethylsilyloxy)-1,3-butadienes, electroneutral equivalents of 1,3-dicarbonyl dianions, results in the formation of 2-alkylidenetetrahydrofurans with a great variety of substitution patterns and functional groups. This includes the synthesis of 2,3'-bifuranylidenes and 7-oxabicyclo[4.3.0]nonanes. The cyclization of dienes with functionalized epoxides containing base-labile groups proceeds with good chemoselectivity. In all reactions, good regio-and E diastereoselectivities are observed. Based on the stereoselectivities observed for reactions of 1,2-disubstituted epoxides, a working hypothesis for the mechanism of the reaction is suggested.

Chiral aldehydes in the synthesis of tetrahydrofurans

1994

Substituted tetrahydrofurans Electrophile-induced cyclisations Halocyclisation reactions Thermodynamically controlled cyclisation Kinetically controlled cyclisation The iodocyclisation of r-alkoxy-a-hydroxy acrylates Reactivity of isopropylidene acrylates Reactivity of r-alkoxy-a-hydroxyacrylates Assignment of stereochemistry Rationalisation of stereochemical outcome Conclusions EXPERIMENTAL REFERENCES APPENDIX Selected IH and 13C nuclear magnetic resonance spectra 99 106 109 110 153 166 An ideal asymmetric synthesis can be characterised by the following features: 8 , 9 a) in addition to high chemical yield, the desired isomer is produced in high stereomeric yield. b) the chiral auxiliary is readily available, inexpensive and recoverable in good yield and undiminished ~urity. c) the chiral product is easily seperated from the chiral auxiliary. d) it is possible to synthesise both enantiomers or diastereomers selectively. With these features as guidelines, two principal synthetic strategies can be used. Firstly, homochirality in the synthesis of a target molecule can be introduced by the use of an external chiral auxiliary reagent. Secondly, a chiral fragment of known absolute configuration can be used. In both respects, nature's II chiral pool II 10 , 11 and the use of enzymes 12-14 play an important role.