Ruthenium‐Catalyzed Enantioselective Hydrogenation/Lactonization of 2‐Acylarylcarboxylates: Direct Access to Chiral 3‐Substituted Phthalides

Abstract

Highly enantioselective tandem hydrogenation/lactonization of various 2‐acylarylcarboxylates including 2‐aroylarylcarboxylates were realized by using [RuCl(benzene)(S)‐SunPhos]Cl as the catalyst under mild reaction conditions. Excellent enantioselectivities (up to 99.6 % ee) and activities (S/C=1000) were obtained. This convenient and practical method enables a direct access to a series of highly optically pure 3‐substituted phthalides that are very important molecules as valuable pharmacological compounds and diversified synthons for medicinal chemistry. Moreover, a gram‐scale reaction was performed to further demonstrate the practicality of this approach.

Synthesis and Antioxidant/Anti-Inflammatory Activity of 3-Arylphthalides

“…Since enzymes act in stereospecific routes leading to pure enantiomers, it is plausible to conclude that the racemization observed in some natural 3-arylphthalides is produced in a post-biosynthetic process. It is also worth noting that although several asymmetric syntheses of 3-arylphthalides can be found in literature [ 34 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], none of them include in their scope the synthesis of compounds bearing phenolic rings at C-3. The easy racemization of 3-arylphthalides which bear orto - or para -hydroxy groups in the aryl ring at C-3 has been explained in terms of the formation at C-3 of a cationic intermediate stabilized by the ability to form quinone methide structures under almost neutral conditions [ 45 ].…”

Progress in the Synthesis of 3-Substituted Phthaides

“…11 的反应, 可获得 90%～99%的收率和 98%～99%的 ee 值. 张兆国 等 [56] 以 Ru-(S)-SunPhos(图 2, L9)为催化剂, 以氢气为还 原剂, 反应 12～48 h, 得到 58%～98%的收率和 34%～ 99.6%的 ee 值, 催化剂的用量仅为底物的 0.5%. 2011 年, 周其林等 [57] 利用 Ir-手性三齿螺环 SpiroPAP(图 2, L10) 络合物催化邻酰基苯甲酸酯的不对称加氢反应, 反应过 程中自发地进行内酯化, 以 98%的产率和 99%的 ee 值得 到了 NBP.…”

The therapeutic potential of novel isobenzofuranones against Naegleria fowleri

“…On the other hand, although there are different approaches to the synthesis of 3-aryl substituted isobezofuranones ( Carlos et al, 2019 ; Chang et al, 2007 ; Hu et al, 2014 ; Huang et al, 2019 ; Lu et al, 2017 ; Mal et al, 2007 ; Phan et al, 2009 ; Touchet et al, 2018 ; Xing et al, 2010 ; Yang and Yoshikai, 2014 ; Yohda and Yamamoto, 2015 ), we wanted to take advantage of our previously reported access to polysubstituted salicylaldehydes ( Tejedor et al, 2011 , 2015 , 2016 ) to design a rapid entry to a small library of this type of substrates. This strategy consists on the synthesis of propargyl vinyl ethers (PVEs) from methyl propiolate and different aldehydes or ketones ( De Armas et al, 2001 ; León et al, 2010 ; Tejedor et al, 2003 ), their subsequent transformation into functionalized salicylaldehydes via a microwave assisted domino reaction triggered by a propargyl Claisen rearrangement, and finally, the metal-free and straightforward generation of the corresponding isobenzofuranones via their acid-catalyzed reaction with electron-rich arenes ( Fig.…”