Stereoselective Prenylation of Aryl- and Heteroaryl Halides: γ-Selective Suzuki–Miyaura Coupling as a Tool for Asymmetric Csp ² –Csp ³ Cross-Coupling

The stereoselective preparation of all carbon quaternary stereogenic centers attached to an aromatic core structure is a long-standing challenge for synthetic chemists, due to the sterically encumbered nature of the central carbon atom. Natural products, like teleocidin A or sporochnol A, carrying a branched geranyl chain feature this special and challenging structural motif. Herein, we present a catalytic system that promotes the asymmetric γ-selective Suzuki-Miyaura cross-coupling of aryl halides and allyl boronic acid esters, to form the desired stereogenic center in one step. The γ-selective coupling approach overcomes the need for a preformed stereogenic center, gives selective access to both stereoisomers, and starts with readily available starting materials. In this study we investigate the scope of the γ-selective cross-coupling reaction and showcase its applicability for late-stage derivatization and natural product synthesis, to provide a further asset in the toolbox of asymmetric synthesis.