Palladium-catalyzed allylic substitution with (?6-arene-CH2Z)Cr(CO)(3)-based nucleophiles.

ABSTRACT: 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 "?-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 (?(6)-C(6)H(5)CHLiR)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 ?(6)-toluene complexes, benzyl amine and ether derivatives (?(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), OR) are also viable pronucleophiles, allowing C-C bond-formation ? 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.

SUBMITTER: Zhang J 

PROVIDER: S-EPMC3241867 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature