Bioinspired total synthesis of tetrahydrofuran lignans by tandem nucleophilic addition/redox isomerization/oxidative coupling and cycloetherification reactions as key steps

Abstract

A very short three-step approach to trans,trans,trans-2,5-diaryl-3,4-dimethyltetrahydrofuran lignans is reported. The carbon skeleton is assembled in a single step based on an unprecedented tandem reaction consisting of 1,2-addition of aryllithium reagents to α,β-unsaturated aldehydes, ruthenium-catalyzed redox isomerization of the resulting alkoxides to enolates and their dimerization triggered by single electron oxidation. The resulting 2,3-dialkyl-1,4-diketones form with moderate to good d/l-diastereoselectivity and are transformed to the target tetrahydrofuran lignans by reduction and diastereoselective cycloetherification.

Total Synthesis of (±)-Cassumunins A–C and Curcumin Analogues

“…(E)-1-(3,4-Dimethoxyphenyl)but-2-en-1-ol (18) 15 Compound 18 was prepared according to the known literature procedure. 15 To a stirred solution of bromoveratrole (1.0 g, 4.60 mmol) in anhyd THF (10 mL) at -78 °C under N 2 atmosphere was added drop-Scheme 7 Synthesis of symmetrical curcumin analogues 1a-k. Reagents and conditions: (i) acetylacetone (1.0 equiv), B 2 O 3 (0.50 equiv), EtOAc, 80 °C, 30 min; (ii) B(OMe) 3 (2.0 equiv), aldehyde derivatives 19a-k (2.0 equiv), n-BuNH 2 (0.2 equiv), EtOAc, 80 °C, 24 h; (iii) 10% HCl, 80 °C, 30 min. Isolated yields after column chromatography: 49-72%.…”

“…13,14 Alcohol 18 was prepared by following the known procedure by trapping the lithiated arene with crotonaldehyde. 15 Compound 17 was subjected to the rearrangement reaction in a sealed OH R R = H, R 1 = H, Cassumunin A (5), 32% R = H, R 1 = Boc, protected Cassumunin A (5a), 46% R = OMe, R 1 = H, Cassumunin B (6), 5% R = OMe, R 1 = Boc, protected Cassumunin B (6a), 48% OMe DMAP (0.1 equiv), Et 3 N (1.5 equiv), Boc 2 O (1.5 equiv), CH 2 Cl 2 , 0 °C, 1 h, 97%…”

Advances in the Synthesis of Lignan Natural Products

“…Based on a tandem nucleophilic addition/Ru-catalyzed isomerization/SET oxidation/radical dimerization strategy [62], Jahn and coworkers reported a bioinspired total synthesis of multiple lignans in 2018 (Scheme 7) [63]. Using bromide 42 as the substrate, a smooth unprecedented tandem 1,2-nucleophilic addition/Ru-catalyzed isomerization/SET oxidation/radical dimerization afforded 1,4-diketone 43 with acceptable diastereoselectivity.…”

Stereoselective Synthesis of Tetrahydrofuran Lignans

“…In 2018, a very short three-step approach for a racemic synthesis of 2,3-anti-3,4-anti-4,5-anti-and 2,3-syn-3,4anti-4,5-anti 2,5-diaryl-3,4-dimethyltetrahydrofurans was reported by Jahn and co-workers (Scheme 22). 26 The carbon skeleton was assembled in a single step based on an unprecedented tandem reaction consisting of 1,2-addition of aryllithium reagents to α,β-unsaturated aldehydes, rutheniumcatalyzed redox isomerization of the resulting alkoxides to enolates, and their dimerization triggered by single electron oxidation. The resulting 2,3-dialkyl 1,4-diketones were formed (41-68% yields) with moderate to good diastereoselectivity (dr 3-4.5:1) and were transformed into the target tetrahydrofuran lignans by reduction of the 1,4-diketone Scheme 21 Systematic synthesis of (2S,3R,4S,5S)-and (2S,3R,4R,5R)-talaumidin…”