title: Palladium-catalyzed allylic substitution with (η6-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 "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 (η(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 η(6)-toluene complexes, benzyl amine and ether derivatives (η(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), 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.
authors: Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
authors: Jiadi
authors: J
authors: Zhang
authors: Corneliu
authors: C
authors: Stanciu
authors: Beibei
authors: B
authors: Wang
authors: Mahmud M
authors: MM
authors: Hussain
authors: Chao-Shan
authors: CS
authors: Da
authors: Patrick J
authors: PJ
authors: Carroll
authors: Spencer D
authors: SD
authors: Dreher
authors: Patrick J
authors: PJ
authors: Walsh
mesh_terms: D002384:Catalysis; D002857:Chromium / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*
chemical_list: D002857:Chromium; D010165:Palladium