Electrophilic Cyanation Using Lewis Acidity of Organoboron Compounds

Nitriles are useful synthetic intermediates because the cyano group is a versatile functional group that can be easily converted to nitrogen or oxygen functional groups. We have found that boron Lewis acids can effectively activate umpolung-type (electrophilic) cyanating reagents through the coordination of their cyano group to the boron center and have achieved various types of electrophilic cyanation reactions. For example, Lewis acidic activation of a hypervalent iodine reagent containing a transferable cyano group with tris(pentafluorophenyl)borane (B(C6F5)3) enabled the electrophilic cyanation of silyl enol ethers to provide β-ketonitriles. In addition, boron enolates derived from 9-borabicyclo[3.3.1]nonane (9-BBN) were found to undergo highly efficient electrophilic cyanation with N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) and p-toluenesulfonyl cyanide (TsCN), which would proceed through a six-membered ring transition state. This approach was extended to the electrophilic cyanation of allylic boranes to provide β,γ-unsaturated nitriles, a process that is applicable to the construction of allylic quaternary carbon centers. Furthermore, the stereospecific intermolecular cyanofunctionalization of alkenes by boron Lewis acid activation of suitable bifunctional electrophilic cyanating reagents has also been realized. The use of TsCN and cyanogen bromide (BrCN) allows for bromocyanation and oxycyanation, respectively. The methods developed have significantly expanded the scope of application of the electrophilic cyanation method, allowing for the synthesis of unique nitriles that are difficult to synthesize by existing methods.