Rapid Access to Benzofuran‐Based Natural Products through a Concise Synthetic Strategy

Abstract

A concise strategy is described for the synthesis of ailanthoidol (1), egonol (2), homoegonol (3), demethoxyegonol (4), demethoxyhomoegonol (5), and stemofuran A (6). This approach involves a Pd‐catalysed domino cyclization/coupling process using triarylbismuth reagents for the generation of the benzofuran core. Subsequent structural modifications then give the final targets. The high yielding synthesis of the recently isolated natural products egonol‐9(Z)‐12(Z)‐linoleate (2a), 7‐demethoxyegonol‐9(Z)‐12(Z)‐linoleate (4a), and 7‐demethoxy‐egonol‐9(Z)‐oleate (4b) are also reported.

Last Decade of Unconventional Methodologies for the Synthesis of Substituted Benzofurans

“…A seminal strategy was reported by Lautens et al, in 2009, in which 2-bromobenzofurans were generated by a Cu-catalyzed cyclization of 2-(2,2-dibromovinyl)-phenols [66]. The same approach was used by Kim's group, to synthesize different natural products [67,68], while recently, Rao et al explored the application of a Pd-catalysed domino cyclization/coupling protocol in a pooled approach for the synthesis of benzofuran natural products [69,70] (Scheme 10).…”

Recent Progress in Palladium-Catalyzed Cascade Cyclizations for Natural Product Synthesis

“…Rao and Murty predicted that the 2-arylbenzofuran core could be easily formed by the Pd-catalyzed furan formation/cross-coupling cascade of vinylidene dibromide 67 (Scheme 13). 26 The dibromide was prepared from o-vanillin (66) in a three-step sequence involving p-iodination of the hydroxy group, a Heck reaction with ethyl acrylate, and olefination of the formyl group using CBr 4 /PPh 3 . The authors chose triarylbismuth for the cross-coupling step due to its advantages in higher and multiple reactivities (with three aryl groups on the metal) over other organometallic reagents.…”

Palladium-Catalyzed Cross-Coupling of Arenediazonium Salts with Organoindium or Organobismuth Reagents

“…Tris(3,5-dimethoxyphenyl)bismuthane (7b). 12 Starting from 3,5-dimethoxybromobenzene (1.075 g, 5.00 mmol) compound 7b (354 mg, 0.57 mmol, 57%) was obtained: off-white solid, mp 84 -86 °C; 1 H NMR (400 MHz, CDCl3) δ 6.97 (d, J = 2.2 Hz, 6H), 6.36 (t, J = 2.2 Hz, 3H), 3.71 (s, 18H); 13 Tris(3-methoxyphenyl)bismuthane (7c). 9 Starting from 3-methoxybromobenzene (9.35 g, 6.28 mL, 50.00 mmol) compound 7c (2.89 g, 5.45 mmol, 55%) was obtained: orange-coloured solid, mp 84 -87 °C; 1 H NMR (400 MHz, CDCl3) δ 7.30-7.28 (m, 3H), 7.28-7.24 (m, 6H), 6.79 -6.74 (m, 3H), 3.63 (s, 9H); 13 Tris(2,4-difluorophenyl)bismuthane (7d).…”