Heyyyy, Umpolung!

A bond between two electrophilic or two nucleophilic atoms can be something of a pain in the ass. To a first approximation, the old formula “nucleophile attacks an electrophile to form a bond” breaks down here, because one of the reaction partners is missing! A common solution to this problem is umpolung, or inversion of polarity. The philicity of one of the reactive atoms is inverted through some kind of functional group transformation, then some kind of polar substituion reaction is run, and finally the initial functional group transformation is undone to give the atom back its original polarity.

A classic example of umpolung is the use of dithiols (HS-R-SH) to convert electrophilic aldehydes to nucleophilic dithianes. When a dithiol (HS-R-SH) reacts with an aldehyde with loss of water, a dithiane (RS-CHR’-SR) initially forms. Deprotonation of these leads to superb nucleophiles, which can react with all manner of electrophiles by SN2, etc. Conversion of the dithiane back to a carbonyl leads overall to an electrophile-electrophile connection.

Maruoka and friends at Kyoto University have recently demonstrated an asymmetric variant of another class of umpolung transformations: the use of aza-enamines as acyl anion equivalents. Take an aldehyde and react it with an N,N-dialkylhydrazine (H2N-NR2) under dehydration conditions. The result is initially an imine with an NR2 group hanging off the sp2 nitrogen, also known as an “aza-enamine,” since it looks like an enamine with a nitrogen shoved in where carbon should be. It’s possible to draw a very nice resonance structure for this molecule that puts a negative charge on the former carbonyl carbon and a positive charge on the “hanging” nitrogen. True to the old adage, the second best resonance structure is the one that represents the molecule’s reactivity, and electrophiles are attacked by the former carbonyl carbon. After deprotonation a substituted aza-enamine remains. Hey, a picture’s worth a thousand words.


The group used ozonolysis to effect regeneration of the carbonyl group. The electrophilic partner was an N-Boc imine because OMGZ CHIRAL AMINO ACIDS YAYZORS!

The catalyst they used was a straight-up organic binaphthyl diacid derivative. No metals in there at all! :’-(

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