A Cascade Coupling Strategy for One‐Pot Total Synthesis of β‐Carboline and Isoquinoline‐Containing Natural Products and Derivatives

Abstract

Multi-birds with one stone: A cascade coupling strategy was developed for the synthesis of β-carbolines. The method can direct the synthesis of β-carboline and isoquinoline-containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme).

Synthesis of Isoquinolinones via Regioselective Palladium-Catalyzed C–H Activation/Annulation

“…Next, common solvents, such as THF, DMF, and 1,2-dichloroethane, were screened. Toluene proved to be the best choice, while the reactions in other solvents were less effective (ClCH 2 CH 2 Cl) or totally ineffective (DMF, THF) (entries [15][16][17].…”

“…Traditionally ortho-difunctionalized benzene starting materials are required for the construction of the heterocylic ring system [16,17]. A more general and efficient approach involves annulation of mono-functionalized arene with conventional synthetic methods, such as rearrangement [17,18], Fridel-Crafts reaction and ortho-lithiation, etc. [19,20].…”

Pd(OAc)2-catalysed regioselective alkoxylation of aryl (β-carbolin-1-yl)methanones via β-carboline directed ortho-C(sp2)–H activation of an aryl ring

“…Subsequently we observed that increasing the amount of TFA from 0.5 equiv to 1.0 equiv enhanced the yield of 4aa to 55% (entry 16). Finally we tested PdCl 2 and Pd(TFA) 2 instead of Pd(OAc) 2 as the palladium source and discovered that 4aa was isolated in 34% and 46% yield, respectively (entries [23][24]. Reducing the temperature of the reaction from 80 o C to 60 o C was also found to have detrimental effect on the yield of 4aa (entry 18).…”

“…23 During the course of our study, the need to access (2-alkoxy-aryl(hetaryl))(9H-pyrido [3,4-b]indol-1yl)methanone for certain SAR studies was warranted. 24 Notably however it was evident from the literature that though directing group ability to induce palladium-mediated C(sp2)-H functionalization of several azaheterocycles have been examined, there is lack of report on ability of β-carboline to act as the directing group. 24 Notably however it was evident from the literature that though directing group ability to induce palladium-mediated C(sp2)-H functionalization of several azaheterocycles have been examined, there is lack of report on ability of β-carboline to act as the directing group.…”

Concise Synthesis of Multisubstituted Isoquinolines from Pyridines by Regioselective Diels–Alder Reactions of 2‐Silyl‐3,4‐pyridynes

“…[2c] Therefore, the synthesis of isoquinolines has attracted considerable attention from both synthetic and biological perspectives. Although diverse synthetic methods for isoquinolines have been reported, [3][4][5][6] most of them are based on the construction of a pyridine ring on benzene; [4, 5a,c-i] for example, the ring closure at the C1-position of isoquinoline, in the Pictet-Spengler [4] and Bischler-Napieralski reactions, [4] and at the C4-position, in the Pomeranz-Fritsch reaction [4] ( Figure 1). In contrast, the "reverse approach", the construction of a benzene ring on pyridine, has not been investigated in detail.…”