A General Strategy for the Diastereoselective Synthesis of 2,6-Diaryl-3,7-dioxabicyclo[3.3.0]octane Lignans

Abstract

A strategy for the stereoselective synthesis of all the possible diastereoisomers of the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane (furofuran) lignans from a single dihydrofuran precursor is described. The key steps involve a diastereocontrolled templated cationic cyclization followed by stereoselective reduction of the resulting methyl glycoside.

Stereoselective Synthesis of Tetrahydrofuran Lignans via BF3·OEt2-Promoted Reductive Deoxygenation/Epimerization of Cyclic Hemiketal: Synthesis of (−)-Odoratisol C, (−)-Futokadsurin A, (−)-Veraguensin, (+)-Fragransin A2, (+)-Galbelgin, and (+)-Talaumidin

“…The observed epimerization of 9a was rationalized on the basis that Lewis acid activation of the hemiketal 9a by BF 3 ·OEt 2 combined with an inductive effect of the electron-donating Bn group on the C2-aryl substituent effectively competed with slow reduction of the oxocarbenium ion intermediate 8a by Et 3 SiH . On the basis of this rationale, we expected that either fast reduction of 8a or a change of the electron-donating Bn group on the aryl substituent to an electron-withdrawing group would prevent the epimerization of the C2-aryl group…”

Total synthesis of (+)-virgatusin via AlCl3-catalyzed [3+2] cycloaddition

“…The resultant carbenium ions 6 and 7 are stabilized by the strongly electron releasing aryl groups (Scheme 2) and isomerization of this type is precedented. 9,13,[16][17][18][19] The appearance of piperonal (2) but not veratraldehyde in the reaction of 5 and AlCl 3 may be understood in terms of the relative facility of retroaldolization of intermediates 6 and 7. It is apparent that C4 0 is the only non-epimerizable stereocenter and acts as the keystone that regulates the C2 0 /C5 0 stereochemical outcome via what is apparently thermodynamic control.…”

Synthesis of Furofuran Lignans

“…Steel et al have published a series of papers describing an approach to furofuran lignans employing an alkenyl epoxide-dihydrofuran rearrangement. [75][76][77] Alkenyl epoxide 103 was prepared by Darzens condensation of bromocro-tonate 102. The critical rearrangement was effected using flash vacuum pyrolysis to afford dihydrofuryl ester 104 as a mixture of cis/trans-isomers (8:1) (Scheme 35).…”

“…xiii,xiv In more recent work, the same group adaptated the above route to allow access to the furofuran analogues in the exo,exo and endo,exo series by epimerisation of the ester 104 (Scheme 36) to give the trans-isomer 107 (dr >19:1). 76 Repeating the cationic cyclisation-reduction sequence gave endo,exo-furofurans with excellent stereoselectively, whereas selectivity in the exo,exo-series was lower (ca. 4:1).…”