TMSI-Promoted Vinylogous Michael Addition of Siloxyfuran to 2-Substituted Chromones: A General Approach for the Total Synthesis of Chromanone Lactone Natural Products

Abstract

A concise and facile synthetic protocol for the construction of the 2-γ-lactone chromanone skeleton has been achieved through a TMSI-promoted diastereoselective vinylogous Michael addition of siloxyfuran to 2-substituted chromones. The applicability of this method is demonstrated through the rapid access to the total syntheses of (±)-microdiplodiasone, (±)-lachnone C, and (±)-gonytolides C and G.

Synthetic Approaches to 2‐Alkylthiochroman‐4‐ones and Thioflavanones

“…The vinylogous 1,4‐addition of 2 equiv of siloxyfuran to thiochromone in the presence of 1.5 equiv of trimethylsilyl iodide (TMSI) in CH 2 Cl 2 also gave 5‐(4‐oxothiochroman‐2‐yl)furan‐2(5 H )‐one ( 24 ) as a 1:1 diastereomeric mixture (Scheme 13). 28 TMSI, generated in situ from TMSCl and NaI, turned out to be a very effective Lewis acid for the vinylogous 1,4‐addition of 2‐trimethylsilyloxyfuran to thiochromone.…”

A Convergent Synthesis of Gonytolide C Using an Intramolecular Oxa‐Michael Addition

“…The mixture was then extracted with CH 2 Cl 2 (3 × 5 mL) and the combined organic extracts were washed with brine (5 mL), dried with anhydrous Na 2 SO 4 , filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (hexanes/EtOAc, 17:3) to afford 21 (6 34 mmol) in CH 2 Cl 2 (20 mL) at -20°C. BF 3 ·OEt 2 (0.46 mL, 3.67 mmol) was then added dropwise and the resultant mixture was stirred at -20°C for 40 min.…”

“…a siloxyfuran to a dialkylsilyl ditriflate activated benzopyrylium ion was employed as the key step in a concise synthesis of the related tetrahydroxanthones. [5] Recently, Liu et al [6] reported the same addition with improved efficiency and diastereoselectivity using iodotrimethylsilane as the Lewis acid catalyst. During the course of our synthetic studies, Sudhakar and coworkers [7] reported a stereoselective synthesis of gonotylide C (2a) and epi-gonytolide C (2b) via diastereoselective intramolecular cyclisation of an aldol intermediate.…”

“…Recently, a number of reports of synthetic work towards gonytolide C (2a) have been published (Scheme 1). [5][6][7][8] A racemic synthesis of (±)-gonytolide C (2a) and (±)-epi-gonytolide C (2b) was incidentally reported by the Porco group in 2011 en route to a different natural product, before the gonytolides had been isolated. [5] A vinylogous addition of ners were established.…”

Copper Bis(oxazoline)‐Catalyzed Enantioselective Alkynylation of Benzopyrylium Ions

“…Our efforts initially focused on the addition of silyl ketene acetals to benzopyrylium triflates, reactive speciesg enerated in situ from chromenonesa nd silyl triflates. [5] Initiallyi nspired by Porco's success, we took advantage of silanediol anion-bindingc atalysis to control, for the first time, addition reactions of silyl ketene acetals to benzopyrylium triflates affording 2-alkylc hromanones in up to 57 %enantiomeric excess (Scheme 1D). [6] We were delighted to see MancheÇo and co-workers further improved upon these findings, obtainingg reater than 90 %e nantiomerice xcess undert he influence of her triazolium catalysts with select substrates.…”