Carbon monoxide as a reductant: synthesis of indoles by palladium catalyzed reductive cyclization of beta-nitrostyrenes

Several years ago, while investigating the possibility to use beta-nitrostyrenes as aminating agents for olefins following our protocol originally devised for nitroarenes, we found that a cyclization reaction to give indoles was observed instead. Better results were obtained employing palladium as catalyst in place of ruthenium. The reaction conditions were optimized using beta-methyl-beta-nitrostyrene (1a) as substrate and some results with different substrates are reported below. While our work was in progress, Hsieh and Dong reported a similar approach for the synthesis of 3-arylsubstituted indoles from alpha-aryl-beta-nitrostyrenes (R1= H, R2 = Ar in the scheme above). Experimental conditions reported in that paper are milder (100 °C, DMF, 2 bar CO absolute pressure) then ours. We reproduced those results and we confirm they work well for alpha-aryl-beta-nitrostyrenes, but fail almost completely when R1 is not H, whereas our conditions are suitable also in this case. Unlike most reported cyclization reaction affording indoles, our strategy does not require the use of a doubly functionalized arene (e.g. an o-bromoaniline) and in most cases the starting materials can be easily prepared by a Henry reaction.