Dehydration of primary amides to nitriles in water. Late-stage functionalization and 1-pot multistep chemoenzymatic processes under micellar catalysis conditions

Dehydration of primary amides to the corresponding nitriles can be performed in aqueous micelles, without need of significant volumes of organic co-solvent. A variety of substrates, including late-stage functionalized molecules, can be converted utilizing an inexpensive, sacrificial nitrile which can accept an equivalent of water. Catalyst loadings of Pd(OAc)(2), as low as 0.2-0.8 mol%, are possible under these conditions in a completely recyclable medium exhibiting very low E Factors. This process is also amenable to 1-pot, chemoenzymatic catalysis exemplifying the benefits of chemistry in water.

Automated summary

Dehydration of primary amides to nitriles can be achieved in aqueous micelles without the need for large amounts of organic co-solvents. A range of substrates, including functionalized molecules, can be converted using a sacrificial and inexpensive nitrile that can accept one equivalent of water. Catalyst loadings as low as 0.2-0.8 mol% of Pd(OAc)2 are possible in this recyclable medium with very low E Factors. This method is also applicable to one-pot reactions and chemoenzymatic catalysis, showcasing the benefits of chemistry in water.