There is some really nice cycloaddition chemistry coming out of Prof. Rob Britton’s lab at SFU. I just heard Rob speak at the symposium dedicated to the memory of Alan Katritzy. Alan’s passing was a big loss to the community, which is evidenced by the interest his chemistry keeps generating. The chair of our Department, Prof. Rob Batey, together with Prof. Vic Snieckus of Queens University, put together a nice group of speakers to commemorate Alan’s contributions to the science of heterocyclic chemistry. All of this took place in Ottawa, as part of the annual CSC meeting.
Now back to the [4+2] chemistry, which is appropriately (according to Rob Britton), referred to as the Kondrat’eva reaction. It is an interesting process, mainly due to the rare display of cycloaddition behaviour on behalf of the oxazole nucleus. Rob is running these reactions in flow, which makes sense given the volatility of alkene starting materials he uses. The reaction is a wonderful means to put together substituted pyridine rings. If you look at the ones made by Rob, you will see that it is far from obvious how to make them by any other means. In the hands of the SFU team, this chemistry was applied towards the synthesis of bioactive molecules.
While this is very pretty, it would be nice if the substrate scope could be expanded: From looking up the supplementary it looks like the reaction only works reasonably well for cyclopentene, with other cyclic olefins provided around 10% isolated yield. And the conditions are brutal.
I wonder if oxazole-N-oxide could do this kind of reaction, to provide pyridine N-oxides. Maybe after O-methylation or treatment with triflic anhydride could activate it further, as a inverse demand DA substrate. Oxazole-N-oxides are available in one good yielding step, from alpha nitrosated ketones and aromatic aldehydes.
This is a very interesting thought. I like it. The N-oxides might indeed help.