Palladium-catalyzed allylic substitution with (η6-Arene- CH2Z)Cr(CO)3-based nucleophiles

Article abstract of DOI:10.1021/ja208935u

Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to "α-2-propenyl benzyl" motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η⁶-C ₆H₅CHLiR)Cr(CO)₃ nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η⁶-toluene complexes, benzyl amine and ether derivatives (η⁶-C₆H₅CH ₂Z)Cr(CO)₃ (Z = NR₂, OR) are also viable pronucleophiles, allowing C-C bond-formation α to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetalation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions.