Unprecedented 8,9′-Neolignans: Enantioselective Synthesis of Possible Stereoisomers for Structural Determination

Abstract

(+)-Wutaienin (3) and its C-7 methyl ether (4), isolated from Zanthoxylum wutaiense, were found to be unprecedented 8,9'-neolignans containing an (S)-2-(1,1-dimethyl-1-hydroxymethyl)-7-methoxydihydrobenzofuran skeleton. Wutaienin (3) was present in the plant as an inseparable 1:1 mixture of the (7,8)-syn-diastereoisomers. The diastereoisomeric mixture was characterized by comparison with four possible diastereoisomers, which were enantioselectively synthesized from (S)-5-bromo-(1,1-dimethyl-1-hydroxymethyl)-7-methoxydihydrobenzofuran using Evans' oxazolidinone-assisted asymmetric aldol condensation to install the chiral centers at the C-7 and C-8 positions.

Total Asymmetric Synthesis and Stereochemical Confirmation of (+)- and (−)-Lyoniresinol and Its Deuterated Analogues

“…[α] D : −64.0 ( c 1.00, CHCl 3 )]; 1 H NMR (CDCl 3 , 400 MHz): δ 7.36–7.20 (m, 5H), 5.94–5.83 (m, 1H), 5.14–5.02 (m, 2H), 4.71–4.65 (m, 1H), 4.22–4.16 (m, 2H), 3.30 (dd, 1H, J = 13.4, 3.3 Hz), 3.10 (dt, 1H, J = 16.6, 7.7 Hz), 3.01 (dt, 1H, J = 16.6, 7.7 Hz), 2.76 (dd, 1H, J = 13.4, 9.6 Hz), 2.49–2.43 (m, 2H); 13 C­{ 1 H} NMR (CDCl 3 , 100 MHz): δ 172.6, 153.5, 136.7, 135.3, 129.4, 128.9, 127.4, 115.8, 66.2, 55.2, 37.9, 34.8, 28.2. The 1 H and 13 C NMR data were in agreement with the literature values …”

“…R f : 0.46 (4:1 petroleum ether/EtOAc); [α] D : −59.1 (c 0.20, CHCl 3 ) [lit. 46 [α] D : −64.0 (c 1.00, CHCl 3 )]; 1 13 C NMR data were in agreement with the literature values. 46 (R)-4-Benzyl-3-((S)-2′-((R)-hydroxy(4‴-isopropoxy-3‴,5‴dimethoxyphenyl)methyl)pent-4′-enoyl)oxazolidin-2-one, 14.…”

“…The solvent was removed in vacuo to obtain a crude oil, which was then purified by flash column chromatography (4:1 petroleum ether/EtOAc) to afford the title product 12 as pale yellow oil (4.00 g, 77%). R f : 0.46 (4:1 petroleum ether/EtOAc); [α] D : −59.1 ( c 0.20, CHCl 3 ) [lit . [α] D : −64.0 ( c 1.00, CHCl 3 )]; 1 H NMR (CDCl 3 , 400 MHz): δ 7.36–7.20 (m, 5H), 5.94–5.83 (m, 1H), 5.14–5.02 (m, 2H), 4.71–4.65 (m, 1H), 4.22–4.16 (m, 2H), 3.30 (dd, 1H, J = 13.4, 3.3 Hz), 3.10 (dt, 1H, J = 16.6, 7.7 Hz), 3.01 (dt, 1H, J = 16.6, 7.7 Hz), 2.76 (dd, 1H, J = 13.4, 9.6 Hz), 2.49–2.43 (m, 2H); 13 C­{ 1 H} NMR (CDCl 3 , 100 MHz): δ 172.6, 153.5, 136.7, 135.3, 129.4, 128.9, 127.4, 115.8, 66.2, 55.2, 37.9, 34.8, 28.2.…”

“…46 [α] D : −64.0 (c 1.00, CHCl 3 )]; 1 13 C NMR data were in agreement with the literature values. 46 (R)-4-Benzyl-3-((S)-2′-((R)-hydroxy(4‴-isopropoxy-3‴,5‴dimethoxyphenyl)methyl)pent-4′-enoyl)oxazolidin-2-one, 14. To a stirred solution of 12 (1.40 g, 5.40 mmol, 1.0 equiv) in distilled EtOAc (20 mL) under an inert atmosphere of nitrogen were added anhydrous MgBr 2 •OEt 2 (279 mg, 1.08 mmol, 0.2 equiv), Et 3 N (1.51 mL, 10.8 mmol, 2.0 equiv), and then a solution of 10 (1.33 g, 5.94 mmol, 1.1 equiv) in distilled EtOAc (5 mL).…”

Metal-Free, Regio- and Stereoselective Synthesis of Linear (E)-Allylic Compounds Using C, N, O, and S Nucleophiles

“…To highlight this, we prepared the unnatural α-amino acid precursor 5 from allylbenzene ( 1 ) in three simple steps (eq 2). Likewise, we prepared the core of wutaienin by reduction of 4i , which could be prepared in two steps, in 91% yield with 3:2 dr (Scheme , eq 3).…”