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.