Herein we describe the use of synergistic Pd and Cu catalysis for stereodivergent coupling reactions between 1,3-dienes and aldimine esters. By using different enantiomers of the two metal catalysts, all four stereoisomers of the coupling products, which have two vicinal stereocenters, could be accessed with high diastereo-and enantioselectivity. This atom-economical cross-coupling reaction has a wide substrate scope and good functional group tolerance. Our work highlights the power of synergistic catalysis for asymmetric coupling reactions involving Pd-hydride catalysts.A s an atom-economical strategy for C−C bond formation, coupling reactions between enols/enolates and unsaturated hydrocarbons with catalysis by transition-metal hydrides (M-H) have been attracting increasing attention. 1 These reactions are initiated by addition of M-H to the unsaturated hydrocarbon to form an electrophilic π-allyl metal intermediate, which reacts with the enolizable carbonyl compound to form a C−C bond (Scheme 1A). Substantial progress on asymmetric versions of these reactions has been made. 2−4 However, controlling the stereochemistry when two contiguous stereocenters are generated by these methods remains a formidable challenge; Dong and co-workers reported the only successful example to date. 5 These investigators developed a cooperative system involving Rh−H and Jacobsen's amine for stereodivergent coupling of aldehydes with alkynes. Inspired by this work, as well as recent advances in Ir-catalyzed stereodivergent allylic alkylation reactions, 6−8 we herein report a protocol for asymmetric coupling reactions between 1,3-dienes and aldimine esters with synergistic catalysis 9 by Pd and Cu; all four possible stereoisomers of the coupling products could be obtained regio-, enantio-, and diastereoselectively by using various combinations of different enantiomers of the two catalysts.Pioneering work by Malcolmson and co-workers demonstrated that Pd-phosphinooxazoline (Pd-PHOX) catalysts can be used to accomplish the addition of various activated Cpronucleophiles to 1,3-dienes with high enantioselectivity. 2d,e However, these investigators did not evaluate less reactive pronucleophiles, 10,11 such as amino acid derivatives. Zhou et al. reported a Ni(0)-catalyzed coupling of 1,3-dienes with simple ketones, but nearly 1:1 mixtures of diastereomers were obtained when two stereocenters were generated. 4 We

For nearly 30 years, considerable research effort has been focused on the development of methods for catalytic (3 + 2) cycloaddition reactions of palladium-oxyallyl species with alkenes. However, because C−O bond formation is kinetically favored, the (3 + 2) cycloadditions achieved to date have involved C−O reductive elimination. We herein report a method of lithium triflate-promoted (3 + 2) cycloaddition reactions of palladiumoxyallyl species with 1,3-dienes that proceed via a pathway terminated with C−C bond formation to give a five-membered carbocycle. Coordination of the lithium ion with the alkoxide moiety disrupts the C−O reductive elimination and forms a metalenolate tethered π-allyl-Pd. The π-allyl-Pd moiety then accepts intramolecular allylic attack from the enolate moiety to form carbocyclic products. Furthermore, by tuning the steric properties of the palladium ligand, we could also accomplish the competing (4 + 3) cycloadditions, and thus this method provides regiodivergent access to both cyclopentanones and cycloheptanones. The reaction mechanism was investigated by DFT calculation and the origins of the regioselectivities of the cycloaddition were rationalized.

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