Gold(I)-Catalyzed Cycloisomerization–Indole Addition Cascade: Synthesis of 3(2H)-Furanone-Incorporated Unsymmetrical 3,3′- Bis(indolyl)methanes

Abstract

An unprecedented Au­(I)-catalyzed domino intramolecular carbonyl-alkyne cyclization/indole addition strategy has been disclosed here. This generalized strategy enables the synthesis of 3­(2H)-furanone-incorporated unsymmetrical bis­(indolyl)­methanes with generation of a stereocenter at the furanone junction from easily accessible indole-tethered ynediones. In addition, this present protocol could also be extended for the synthesis of a number of indolyl-(hetero)­arylmethanes by employing a variety of (hetero)­arenes as a nucleophile coupling partner.

Iodocycloisomerization/Nucleophile Addition Cascade Transformations of 1,2-Alkynediones

“…Alongside indole-bearing ynediones, we extended our method to a variety of other 1,2-alkynediones. Phenyl-substituted ynedione, which was found to be inert in the Au­(I)-catalyzed reaction, reacted smoothly, yielding the desired product 4a in good yield. Subsequently, a variety of phenyl ynediones containing aryl ( 4b and 4c ), heteroaryl ( 4d ), and cycloalkyl ( 4e ) substitutions at the alkyne terminus were found to be suitable for this transformation (Scheme ).…”

“…On the basis of the hypothesis discussed above, we have recently developed a Au(I)-catalyzed cycloisomerization/ indole addition cascade approach for the synthesis of unsymmetrial bis(indolyl)methanes from ynediones that follows a selective 1,4-nucleophile addition pathway (Scheme 1C). 6 This method has a limitation, it works only with the indole-bearing 1,2-alkynedione substrates as the nucleophilic push from the electron rich indole ring was found to be essential for the transformation. Thus, a more general method for a similar cascade transformation is needed.…”

“…Accordingly, 1,2-addition of a nucleophile would furnish the 3­(2 H )-furanone core tethered to a dearomatized indole functionality, whereas 1,4-addition and successive indole rearomatization would provide the 3­(2 H )-furanone with an intact indole moiety. On the basis of the hypothesis discussed above, we have recently developed a Au­(I)-catalyzed cycloisomerization/indole addition cascade approach for the synthesis of unsymmetrial bis­(indolyl)­methanes from ynediones that follows a selective 1,4-nucleophile addition pathway (Scheme C) . This method has a limitation, it works only with the indole-bearing 1,2-alkynedione substrates as the nucleophilic push from the electron rich indole ring was found to be essential for the transformation.…”

Divergent Synthesis of 3-Pyrrolidin-2-yl-1H-indoles, Symmetric and Unsymmetric Bis(Indolyl)Methanes (BIMs) through Photocatalyzed Decarboxylative Coupling/Friedel–Crafts Alkylation Reaction

“…Synthetic methods containing these motifs have therefore been widely studied. Nevertheless, the majority of synthetic methods available are for accessing symmetrical BIMs, whereas methods for accessing the unsymmetrical BIMs are more challenging. ,− The conditions developed were employed to obtain unsymmetrical BIMs 5 using 3.0 equiv of KHSO 4 as an acid additive from 3-pyrrolidin-2-yl-1 H -indole 3a and various indoles 2 . Next, the scope of substituted indoles was investigated (Scheme ).…”

Indolyl‐Ynones: Building Blocks for Molecular Diversity

“…Sawant et al have unveiled a novel domino intramolecular carbonyl-alkyne cyclization/indole addition approach (Scheme 27). [33] This innovative strategy enables the synthesis of unsymmetrical bis(indolyl)methanes incorporating a 3(2H)-furanone moiety, along with the introduction of a stereocenter at the furanone junction. Remarkably, this methodology employs easily accessible indole-tethered ynediones as starting materials.…”