Directing Group Assisted Unsymmetrical Multiple Functionalization of Arene C−H Bonds

Abstract

Multiple C−H bond functionalizations promptly install diverse groups on the molecular framework and consequently fabricate complex molecular entities. This review briefly surveys the conceptual development of directing group assisted unsymmetrical multiple functionalization of arene C(sp2)−H bonds, which is exceedingly appealing and highly important.

Sulfur and Nitrogen Modulated One-Pot Double Annulation of Arenes

“… , Interestingly, the desired 6,6-fused thiopyrano-isoquinoline ( 3a ) was formed in 29% yield under the catalytic conditions {[RuCl 2 ( p -cymene)] 2 (5.0 mol %), Cu­(OAc) 2 ·H 2 O (1.0 equiv), and AgSbF 6 (20 mol %) in 1,2-dichloroethane (DCE) at 120 °C for 24 h} (entry 1, Table ). Screening of acetate sources [NaOAc, KOAc, CsOAc, Mn­(OAc) 2 ·3H 2 O, Zn­(OAc) 2 ·2H 2 O, AgOAc, and anhydrous Cu­(OAc) 2 ] revealed that Cu­(OAc) 2 was most effective (entries 2–8), providing 3a in 34% yield (entry 8). , …”

“…On the basis of the above mechanistic studies, the plausible mechanism is proposed (Figure ). − The ligand exchange between [RuCl 2 ( p -cymene)] 2 , AgSbF 6 , and Cu­(OAc) 2 at first produces the active Ru­(II) catalyst. The coordination of the “S” moiety to the active catalyst and the activation of the proximal C–H bond of aryl thioamides forms a five-membered Ru-intermediate I .…”

“…Owing to the high atom and step economy, the directing group (DG)-assisted TM-catalyzed oxidative annulation of (hetero)­arenes with alkynes has emerged as the most efficient route to access novel complex heterocycles from readily available precursors . Despite the widespread popularity of this method, most of the annulations are confined to the construction of oxygen- and nitrogen-containing polycyclic heteroarenes. − In this regard, amide, imine, nitrile, hydroxyl, and carbonyl DGs are extensively uncovered for the direct annulation of inert C–H bonds. , On the other hand, thioamide-directed activation and functionalization of inert C–H bonds are rare . This is probably because the strong binding ability of S to the TM, high lability of S to oxidation, and competition between S and N coordination to the metal catalyst make this process difficult (Figure A) …”

Harnessing sulfur and nitrogen in the cobalt(iii)-catalyzed unsymmetrical double annulation of thioamides: probing the origin of chemo- and regio-selectivity

“…Along these lines, the heteroatom-guided double annulation of arenes CH bonds with alkynes has been realized by the coordination of 'N' to Ru, Rh, and Ir. [14][15][16][17][18][19][20][31][32] In that respect, the coordination of amide 'N' over 'O' has granted access to polycyclic amides, wherein a metalated isoquinolone species plays a crucial role. 3337 With thioamides, such complexation of 'N' to TM over 'S' provides isoquinolones, as metalatedthioisoquinolone is prone to hydrolysis under such oxidative conditions (Fig.…”

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

“…Multiple reactive sites or components may interact on each other, making it difficult to balance the reactivity and selectivity for several successive steps in one pot. In the past two decades, we have witnessed blossoming of new synthetic toolkits including C-H functionalization (Chen and Youn, 2012;Yamaguchi et al, 2012;Gulías and Mascareñas, 2016;Abrams et al, 2018;Sambiagio et al, 2018;Zheng and Hua, 2018;Ghosh et al, 2020), palladium catalysis (Chinchilla and Najera, 2014;Düfert and Werz, 2016;Trost and Min, 2020), and gold catalysis (Fürstner, 2009;Zhang et al, 2014;Dorel and Echavarren, 2015;Pflästerer and Hashmi, 2016;Marín-Luna et al, 2019). These emerging synthetic methodologies enable new cascade reaction in mild conditions via substrate activation (for alkynes, their reaction partners, or both of them), thus expanding the utilization of alkynes for syntheses of polyheterocycles with higher efficiency and diversity.…”