One‐Pot Trimetallic Relay Catalysis: A Unified Approach for the Synthesis of β‐Carbolines and Other [c]‐Fused Pyridines

Abstract

A divergent strategy is presented for the synthesis of 1,3-di- and 1,3,4-trisubstituted β-carbolines through an unprecedented one-pot triple-orthogonal-metal relay catalysis, and 1,3-disubstituted 4-hydroxy-β-carbolines through a one-pot bimetallic relay catalysis from readily accessible 3-(2-aminophenyl)-5-hexenyn-3-ols. These strategies were elaborated to enable the synthesis of benzofuro[2,3-c]pyridines, benzothieno[2,3-c]pyridines, and isoquinolines, which otherwise require multistep synthesis.

Multicatalytic Approach to One-Pot Stereoselective Synthesis of Secondary Benzylic Alcohols

“…Because the bulk of organic solvents is used for isolation and purification of synthetic intermediates, rather than as the medium of the actual chemical reactions, procedures that execute multiple synthetic steps in a one-pot fashion are advantageous from the efficiency standpoint. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] The economy of one-pot synthesis 21 that connects stoichiometric and catalytic reactions, with or without limited intermediary work-up, proved highly beneficial for the synthesis of complex molecules, 22 including natural products and pharmaceuticals. [23][24][25] However, the development of one-pot protocols with multiple transition-metal catalyzed reactions operating in one vessel remains a challenge.…”

Hypothesis‐Driven Palladium‐Catalyzed Transformations for the Construction of New Molecular Architectures

“…[32] In 2016, we reported a divergent one-pot trimetallic strategy to access 1,3-di-and 1,3,4-trisubstituted β-carbolines 61 from the designed enynols 60, Scheme 15. [33] The synergistic action of AgOAc, BiCl 3 , and Pd(OAc) 2 provided the privileged structures in good to excellent yields. From the mechanistic point of view, the enynol 60, by undergoing Ag-catalyzed 5-exo-dig cyclization (intramolecular hydroamination), generates indoline alcohol AD, which follows a 1,3-allylic alcohol isomerization and nucleophilic dehydrative azidation in the presence of BiCl 3 for the formation of AE.…”

“…Our group also contributed to developing several bi‐ and trimetallic orthogonal tandem catalytic systems to access intricate molecular architectures [32] . In 2016, we reported a divergent one‐pot trimetallic strategy to access 1,3‐di‐ and 1,3,4‐trisubstituted β‐carbolines 61 from the designed enynols 60 , Scheme 15 [33] . The synergistic action of AgOAc, BiCl 3 , and Pd(OAc) 2 provided the privileged structures in good to excellent yields.…”

Tandem Annulations of Propargylic Alcohols to Indole Derivatives

“…The development of orthogonal relay catalytic approaches has received tremendous attention due to rapid and efficient construction intricate molecular architectures [17] . The group of Ramasastry reported a triple‐orthogonal‐metal relay catalysis that integrated Ag(I), Bi(III) and Pd(II) catalysts towards the preparation of α , β ‐carbolines via an one‐pot cascade involving intramolecular hydroamination, Friedel‐Crafts‐type dehydrative azidation, and intramolecular azide‐alkene [3+2] cycloaddition of the resulting, ϵ , ω ‐unsaturated azide to form a pyridine ring [18a] . A wide range of 1,3‐disubstituted β ‐carbolines and 1,3,4‐trisubstituted β ‐carbolines were produced from enynols 51 in good to excellent yields (top, Scheme 12).…”