Lanthanum-Catalyzed Double Hydrophosphinylation of Nitriles

A new lanthanum-based catalyst was shown to be effective for the double hydrophosphinylation of unactivated nitriles under very mild conditions. Surprisingly, the lanthanum catalyst gave two regioisomeric products depending on the nature of the starting nitrile. Primary alkyl nitriles undergo 1,1-addition to give products with a new PCP linkage and concomitant formation of a primary amine. Under the same conditions, secondary alkyl and aryl nitriles instead produced 1,2-addition products, where 1 equiv of the phosphine oxide was added to the carbon, while a second equivalent added to the nitrogen of the nitrile, resulting in a PCNP framework. Further investigation of the catalytic cycle yielded evidence that all nitriles first undergo 1,1-addition (deemed the kinetic product) that then undergoes isomerization to the final unsymmetric addition product (the thermodynamic product). All catalytic reactions were run neat or with very little solvent, required little workup, and had high to moderate yields.