Enantioselective Synthesis of Isoflavanones and Pterocarpans through a Ru^II‐Catalyzed ATH‐DKR of Isoflavones

Abstract

Noyori‐Ikariya RuII complexes promoted the one‐pot C=C/C=O bonds reduction of isoflavones using sodium formate as the hydrogen source through Asymmetric Transfer Hydrogenation‐Dynamic Kinetic Resolution (ATH‐DKR). Due to the neutral conditions employed, isoflavones with different substituents at the 2’‐position of B‐ring (H, OH, OMe and Br) were successfully reduced. Ten cis‐3‐phenylchroman‐4‐ols were selectively obtained (>20 : 1 dr) in good yields (up to 86 %) and excellent enantioselectivities (up to >99 : 1 er). The synthetic applications of these chiral compounds were also demonstrated. Enantioenriched isoflavanones were obtained under mild metal‐free oxidation of the cis‐3‐phenylchroman‐4‐ols while pterocarpans were synthesized by two strategies: an acid‐catalyzed cyclization and a novel approach based on a Pd‐catalyzed C−O intramolecular cross‐coupling reaction.

Enantioselective Synthesis of Flavonoids and Their Diverse Applications in Nutrition, Health, and Medicine: A Mini Review

“…For asymmetric isoflavanones, which have important physiological functions, Gaspar et al extended the use of ATH-DKR to produce cis-3-phenylchroman-4-ols. [103] Through base-promoted retro-oxa-Michael addition and palladium-catalyzed asymmetric allylic alkylation, the research showed how to achieve up to 99 % enantioselectivities in 2,3disubstituted flavonoids through dynamic kinetic resolution. Using this technique, two contiguous stereocenters, which included a quaternary stereogenic center, were created on nucleophile flavonoids at the same time.…”

Stereoselective Synthesis of Flavonoids: A Brief Overview

“…More recently, in this thematic field of stereoselective synthesis, and inspired by Metz et al [ 112 , 113 ] and their previous works [ 114 ], Gaspar et al [ 115 ] were able to enlarge the scope of ATH-DKR to obtain cis -3-phenylchroman-4-ols and, subsequently, use them as intermediates for the synthesis of chiral isoflavanones, which possess crucial biological activities [ 116 ]. With the aim of accomplishing their goal, they applied a Noyori–Ikariya ruthenium complex as the catalyst and sodium formate as the hydrogen source to the reaction (first reaction step, Figure 40 ), culminating in the formation of ( R , R )- cis -alcohols in a range between 92% and 99% of the enantiomeric ratio [ 115 ]. Thereafter, they used a Dess–Martin periodinane (DMP) oxidation to synthesise two chiral natural isoflavanones (second reaction step, Figure 40 ), maintaining the enantiomeric ratios previously acquired [ 115 ].…”

“…With the aim of accomplishing their goal, they applied a Noyori–Ikariya ruthenium complex as the catalyst and sodium formate as the hydrogen source to the reaction (first reaction step, Figure 40 ), culminating in the formation of ( R , R )- cis -alcohols in a range between 92% and 99% of the enantiomeric ratio [ 115 ]. Thereafter, they used a Dess–Martin periodinane (DMP) oxidation to synthesise two chiral natural isoflavanones (second reaction step, Figure 40 ), maintaining the enantiomeric ratios previously acquired [ 115 ].…”

“…With the aim of accomplishing their goal, they applied a Noyori-Ikariya ruthenium complex as the catalyst and sodium formate as the hydrogen source to the reaction (first reaction step, Figure 40), culminating in the formation of (R,R)-cis-alcohols in a range between 92% and 99% of the enantiomeric ratio [115]. Thereafter, they used a Dess-Martin periodinane (DMP) oxidation to synthesise two chiral natural isoflavanones (second reaction step, Figure 40), maintaining the enantiomeric ratios previously acquired [115]. More recently, in this thematic field of stereoselective synthesis, and inspired by Metz et al [112,113] and their previous works [114], Gaspar et al [115] were able to enlarge the scope of ATH-DKR to obtain cis-3-phenylchroman-4-ols and, subsequently, use them as intermediates for the synthesis of chiral isoflavanones, which possess crucial biological activities [116].…”

“…Thereafter, they used a Dess-Martin periodinane (DMP) oxidation to synthesise two chiral natural isoflavanones (second reaction step, Figure 40), maintaining the enantiomeric ratios previously acquired [115]. More recently, in this thematic field of stereoselective synthesis, and inspired by Metz et al [112,113] and their previous works [114], Gaspar et al [115] were able to enlarge the scope of ATH-DKR to obtain cis-3-phenylchroman-4-ols and, subsequently, use them as intermediates for the synthesis of chiral isoflavanones, which possess crucial biological activities [116]. With the aim of accomplishing their goal, they applied a Noyori-Ikariya ruthenium complex as the catalyst and sodium formate as the hydrogen source to the reaction (first reaction step, Figure 40), culminating in the formation of (R,R)cis-alcohols in a range between 92% and 99% of the enantiomeric ratio [115].…”