Synthesis of Lignans Based on a Borate‐mediated One‐pot Sequential Suzuki‐Miyaura Coupling of Cyclic Boranes

Abstract

Lignans are a group of polyphenolic phytochemicals that possess a large spectrum of chemical structures and biological activities. Here the syntheses of lignans -anwulignan, burseran, dehydroxycubebin, ruburisandrin B, and sesamin -are achieved based on a borate-mediated one-pot sequential Suzuki-Miyaura coupling of cis-and trans-fused bicyclic boranes, which were prepared by diastereoselective cyclic hydroboration of exo-cyclic diene with cyclopentyl-and thexylboranes, respectively. A one-pot sequential Suzuki-Miyaura coupling of each cyclic borate with various aryl bromides initiated by activation of the cyclic borane with the carbon nucleophile provided 2,3-dibenzylbutane derivatives with different aromatic substituents. Finally, the syntheses of naturally occurring lignans were accomplished in several steps from the products of Suzuki-Miyaura coupling.

Recent developments in nickel-catalyzed asymmetric cyclization and cycloaddition of carbonyl-alkynes, cyano-alkynes, and enynes

“…Transformations of the present asymmetric cyclization reaction were used to synthesize chiral natural products, such as dehydroxycubebin, 16 which have potential anticancer activity. 17 Upon using carbonyl–alkyne 7 as a starting material and ( R )-BI-DIME (10 mol%) L2 as a chiral ligand and carrying out the reaction at 70 °C, the cyclization product 8 was obtained in 87% yield and 99% ee.…”

Taming the radical cation intermediate enabled one-step access to structurally diverse lignans

“…Notwithstanding the great progress recorded in the synthesis of lignans 14 , a concise and divergent synthetic approach allowing access to diverse subsets of lignan scaffolds from simple and cheap starting materials is still highly demanded in order to fully exploit the biological potential of these natural products [15][16][17][18][19][20][21] . While the structures of lignans are relatively simple, the control of stereochemistry in the cyclization step remains challenging [22][23][24][25][26] . Inspired by the pioneering work of Yoon [27][28][29] and Nicewicz 30,31 on the visible-light photoredox-catalyzed [2 + 2] and [4 + 2] cycloadditions of styrene derivatives, we recently reported an acridinium salt (Fukuzumi's salt, 16) [32][33][34][35] catalyzed intramolecular formal [4 + 2] cycloaddition of functionalized dicinnamyl ethers 17 to aryltetralin cyclic ethers 18 or 19 under blue LED irradiation (Fig.…”