Four-Component Synthesis of Star-Shaped 2-(Indol-3-yl)pyridine Derivatives in One Pot

Abstract

A protocol for the synthesis of star-shaped 2-(indol-3-yl)pyridine derivatives 4, neat, in the presence of iodine as a catalyst was developed (method A). Based on this strategy, compounds 4-aryl-2-(1H-indol-3-yl)-6-arylnicotinonitriles 6 were synthesized from 3-(cynonoacetyl)indole 1, aromatic aldehyde 2, aromatic ketone 5, and AcONH₄ under the conditions of both methods A (solvent free) and B (using AcOH as solvent). The compounds 4-aryl-2-(1H-indol-3-yl)-6-(thiophen-2-yl)nicotinonitriles 8 were also prepared under the conditions of method B.

GRAPHICAL ABSTRACT

Keywords:

• 3-(Cynonoacetyl)indole
• 2-(indol-3-yl)pyridine
• molecular iodine
• multicomponent reactions

Notes

^a Isolated yield.

^b DDQ (50 mol%) was added.

^a Reaction conditions: 3-(cyanoacetyl)indole 1 (1 mmol), aromatic aldehyde 2 (1 mmol), 3-acetylpyridine 3 (1 mmol), AcONH₄ (1.5 g), iodine (0.1 mmol), 120 °C, neat.

^b Isolated yield.

^c Detected by LC-MS.

^a Isolated yield.

^b Reaction conditions: Method A: 3-(cyanoacetyl)indole 1 (1 mmol), aromatic aldehyde 2 (1 mmol), aromatic ketone 5 (1 mmol), AcONH₄ (1.5 g), iodine (0.1 mmol), 120 °C, neat; Method B: 3-(cyanoacetyl)indole 1 (1 mmol), aromatic aldehyde 2 (1 mmol), aromatic ketone 5 (1 mmol), AcONH₄ (1.5 mmol), iodine (0.1 mmol), AcOH (1.5 ml), refluxing temperature.

^a Reaction conditions: 3-(cyanoacetyl)indole 1 (1 mmol), aromatic aldehyde 2 (1 mmol), 1-(thiophen-2-yl)ethanonene 7 (1 mmol), AcONH₄ (1.5 mmol), iodine (0.1 mmol), AcOH (1.5 ml), refluxing temperature.

^b Isolated yield.