A synthetic route to 1,4-disubstituted tetrahydro-β-carbolines and tetrahydropyranoindoles via ring-opening/Pictet–Spengler reaction of aziridines and epoxides with indoles/aldehydes

Abstract

A route to 1,4-disubstituted tetrahydro-β-carbolines and tetrahydropyrano[3,4-b]indoles in high yields and stereoselectivity via SN2-type ring opening/Pictet–Spengler reaction of aziridines and epoxides with indoles is described.

Palladium-Catalyzed Synthesis of 1-Vinyltetrahydro-β-carbolines and Aza-spiroindolenines: Access to the Syntheses of 1-Vinyl-β-carbolines and Eudistomins Y1 and Y2

“…Among the large number of THBCs, C1-substituted derivatives widely exist in nature as a constituent of indole alkaloids; consequently, there have been many reports on their syntheses including those involving modern transition-metal catalysts (Scheme ). Most of them adopted the well-known Pictet–Spengler (PS) reaction, which however proves less useful when 1-vinyl-substituted THBCs are targeted. Only a few reports exist where N -allyl, allenyl, or propargyl derivatives of tryptamine were exposed to rhodium, gold and palladium catalyst respectively (Scheme a–c), besides other methods , employing oxidative C­(sp 3 )–H olefination at the C1 position of the preformed THBCs.…”

Groebke–Blackburn–Bienaymé multicomponent reaction coupled with unconventional Pictet–Spengler cyclization for the synthesis of imidazo[4,5‐b]pyridine fused polycyclic heterocycles

“…In the third step, compound 12a was reacted with benzaldehyde for the PS cyclization. Most commonly, ptoluenesulphonic acid (p-TSA) is used as a catalyst for this reaction [40,41]. So initially, p-TSA in toluene as a solvent under reflux condition was used.…”

Pictet–Spengler-Based Multicomponent Domino Reactions to Construct Polyheterocycles

“…89 This alternative method involved a cascade process of Groebke-Blackburn-Bienaymé reaction to form the fused adduct, acid-catalyzed Pictet-Spengler cyclization to obtain dihydropyridine, and oxidation by atmospheric O 2 to finally afford a series of In 2020, Wani and coworkers reported that the 1,4disubstituted tetrahydro-β-carbolines and tetrahydropyrano [3,4-b]indoles 105 could be obtained in high yields and stereoselectivity by a simple and efficient method using indoles 102, aziridines or epoxides 103, and benzaldehydes 104 (►Scheme 25). 91 In this report, LiClO 4 -catalyzed ring opening of aziridines and epoxides with indoles was performed in acetonitrile at 85°C for 3 hours, followed by ptoluenesulfonic acid-catalyzed Pictet-Spengler cyclization with benzaldehydes. To improve the efficiency of the Pictet-Spengler cyclization, various reaction parameters were screened.…”