Benzo[f][1,2]oxasilepines in the Synthesis of Dihydro[b]benzofuran Neolignans

Abstract

A short synthesis of neolignans with a dihydrobenzo[b]furan skeleton is described. The strategy is based on a ring-closing metathesis to produce benzo[f][1,2]oxasilepines which are condensed with aromatic aldehydes in a modified Sakurai-Hosomi reaction. Natural dihydrodehydrodiconiferyl alcohol (1) and 3-O-demethyldihydrodehydrodiconiferyl alcohol (2) have been prepared in this way.

Key words

neolignans - dihydrobenzofurans - allyl siloxanes - ring-closing metathesis - Sakurai reaction

References

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11

Use of BH₃·SMe₂, H₂O₂, NaOH produced a mixture of primary (91%) and secondary (9%) alcohols, which were easily separated by column chromatography. Use of bulkier hydroborating agents, like 9-BBN, did not increase the selectivity.

13

Careful column chromatography of compound 3 was needed to avoid silica gel promoted protodesilylation.

17

The aldehyde present in the crude reaction mixture shows the same chromatographic properties as the reaction products. Complete separation could only be achieved through transformation into its carboxylic acid by mild oxidation of the crude reaction mixture with NaClO₂ and extraction with base.

18

The cis/trans ratio proved to be independent of the temperature, concentration, and the number of equivalents of Lewis acid used.

20

The OsO₄ oxidation of 10 cis or 11 cis yielded mixtures of cis/trans aldehydes, which could not be separated due to the fast isomerization of the cis isomers in contact with silica gel.

21

Epimerization was observed during reduction of the cis aldehyde with NaBH₄ in MeOH. LiAlH₄ in THF at -60 °C allowed fast and complete reduction and deprotection of pivaloyl group. No epimerization was observed in these conditions.