There is always a list of synthetic reactions we haven’t performed — and for many reasons – but Derek’s In the Pipeline post on reactions gets me to thinking. I, too, have not run a Baylis-Hillman reaction or how it is often referred to in the literature as the Morita Baylis Hillman reaction (MBHR). It always fascinated me since it is a good way to substitute at the alpha center to an unsaturated electron deficient system.

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MBHR

Certainly seems simple enough. The mechanism is shown below — to illustrate that DABCO is not the only nucleophic base which can be used for the transformation. In fact modifications have been made utilizing phosphines as well. There have been a number of debates on the mechanism for this reaction.

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MBHR mechanism — good to know your pKas

One thing is clear over the years is that most of the publications show slow reaction times, however improvements have been made utilizing ionic liquids, ultrasound and microwave as well as solvent studies. This is where the microwave can step in and generate some more discussion. A recent publication (J Braz Chem Soc 2011) on monacylglycerols utilized microwave irradiation along with some solvent studies. There is a lot of discussion of best pathway to use for the final compounds — protect the glycerol as the acetonide or running the reaction unprotected and finding the right conditions — definitely worth the read because this group uses several substrates under protic and aprotic pathways and generate some interesting results if one were to apply this reaction…..for me it was nice to find a a significant enhancement in reaction time to a 10 min reaction with some modest screening efforts….and also choose which reaction pathway that makes the right sense for the research.

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Reaction performed in aprotic CH3CN

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Reactions with aprotic, protic and polar reaction media

Some additional examples can be found:

Synthetic Communications 2011

Molecular Informatics 2004

Arkivoc 2008 (pdf)

Chemistry Central Journal 2012 (open access)

Something to think about when you want to try a reaction that hasn’t made your list yet. I have some favorites that I want to try — and I am sure all of the readers do as well…..

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