I am going to go to the left side of the ballpark on this one, because if you like this site, small bits and pieces from several posts will show up. A few hints on this one…..remember, I like indoles, cascades, rearrangements —

This indole construction has its’ bottom seated in the intramolecular diels alder of a furan approach (IMDAF). I tip my hat to start to Al Padwa and Peter Wipf for some elegant construction of indoles without some of our more popular transition-metal catalyzed approaches we know look to pull off the shelves (as Henry Rappaport once said to me, as an organic chemist you should never be seduced by commercial availability — a true test it to make it. OK I love that sort of stuff from the giants.

Indoles from this approach: 3,4 from amino furan IMDAF with appropriately position double bonds and 4,5,6- (but particularly the 5-hydroxy for obvious reasons) from the amino furan and IMDAF and a triple bond (remember above — a furan 2-carboxylic acid undergoes a nice Curtius rearrangement to provide 2-amino furans – now I have 2 microwave steps again, just a game I play).

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3,4-Substituted indoles IMADF

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5-hydroxyindoles

Before moving to the microwave the IMDAF reaction was popularized in the 60s — Wasserman, Cram, Herz were doing these when the music was good. Move forward and Al Padwa put some unbelievable touches on the reaction by placing and amino group on the furan system….I have done some reactions with this pendant group and it really can help open what can be made….anyway I have digressed, and if you are interested in these cyclizations or [4+2] cycloadditions take a look at the monograph series Advances in Cycloadditions.

Chem Comm 2009 in this report, Wipf’s group uses the appropriately positioned allylic alcohol with the amino furan in a microwave.  The process shown below produced moderate to good yields of the 4-substituted indoles, but in comparison to straight thermal conditions which only produced decomposition of the starting material.

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Microwave conditions for IMDAF

You should stay tuned to the first 2 schemes with the alkyne and some development on the amino furan moiety (brief reports from the Wipf team indicate they have made tremendous progress in indole construction with some tandem processes that expand the approach). I can’t wait to read the papers Peter.

 

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