Enantioselective Total Synthesis of Chromanone Lactone Homo‐ and Heterodimers

Abstract

A one pot borylation/Suzuki-Miyaura reaction of the 4-bromochromanone lactones 21 and 23, respectively, followed by cleavage of the methyl ether moieties gave the homodimeric chromanone lactones 10 and 11. Reaction of a 1:1 mixture of 21 and 23 under otherwise identical conditions gave a 1:1:2-mixture of the two homodimers 10 and 11 and the heterodimer 12. This is the first example of the preparation of a heterodimeric chromanone lactone. For the enantioselective synthesis of the starting material, phenol 17 was transformed into the chromane 18 using a Wacker-type cyclisation with 99 % ee and 80 % yield.

Chromanone Lactones: A Neglected Group of Natural Products – Isolation, Structure Elucidation, Bioactivity, and Synthesis

“…Procedure for the preparation of hetero dimeric chromanone lactone by the Tietze group. [59] respectively. Dimerization of 179 a using a one pot borylation/ Suzuki-Miyaura reaction gave the dimer 151 b, which has identical NMR spectra and optical rotation as blennolide H isolated by Cai et al [57] This allows to assign its relative and absolute configuration as (2S,9R,10R,2'S,9'R,10'R).…”

“…As expected, the dimerization provided the two already known homo dimeric chromanone lactone 167 and 170 and the new hetero dimeric chromanone lactone 172 in the ratio of 1 : 1 : 2 (Scheme 22). 172 was then transformed into the unprotected hetero dimeric chromanone lactone 173 , which unfortunately was not identical with paecilin A [59] …”

“…172 was then transformed into the unprotected hetero dimeric chromanone lactone 173, which unfortunately was not identical with paecilin A. [59] The Tietze group also attempted the synthesis of the enantiomer of phomopsis-H76A (139, Scheme 23), starting from compound 174 which they prepared utilizing a similar procedure as the one used for the synthesis of gonytolide C (Scheme 11) employing an enantioselective Wacker oxidation, dihydroxylation and methylation. [60] Cyclization of the product produced the desired monomeric chromanone lactone 175 which was iodinated employing BnNMe 3 ICl 2 to give a mixture of 176 a-c (Scheme 23B).…”

“…[60] As the monomeric units in 151 had the same constitution as paecilin B ( 15 Procedure for the preparation of homo dimeric chromanone lactone by the Tietze group. [59] Scheme 22. Procedure for the preparation of hetero dimeric chromanone lactone by the Tietze group.…”

“…Scheme 21. Procedure for the preparation of homo dimeric chromanone lactone by the Tietze group [59]. …”