Asymmetric synthesis from terminal alkenes by cascades of diboration and cross-coupling

Abstract

Amongst prospective starting materials for organic synthesis, terminal (monosubstituted) alkenes are ideal. In the form of α-olefins, they are manufactured on enormous scale and they are the core product features from many organic chemical reactions. While their latent reactivity can easily enable hydrocarbon chain extension, alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these impressive attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic α-olefins in >90% ee and, with the exception of site-controlled isotactic polymerization of α-olefins,1 none of these processes result in chain-extending C-C bond formation to the terminal carbon.2, 3, 4, 5, 6 Herein, we describe a strategy that directly addresses this gap in synthetic methodology and present a single-flask catalytic enantioselective conversion of terminal alkenes into a range of chiral products. These reactions are enabled by an unusual neighboring group participation effect that accelerates Pd-catalyzed cross-coupling of 1,2-bis(boronates) relative to nonfunctionalized alkyl boronate analogs. In tandem with enantioselective diboration, this reactivity feature connects abundant alkene starting materials to a diverse array of chiral products. Importantly with respect to synthesis utility, the tandem diboration/cross-coupling reaction (DCC reaction) generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), employs low loadings (1–2 mol %) of commercially available catalysts and reagents, it offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology.

Stereospecific Couplings of Secondary and Tertiary Boronic Esters

“…[9] In 2014 Morken and co-workers disclosed a similar mechanistic study for the Suzuki-Miyaura cross-coupling of 1,2-diboryl ester substrates. [10] Also in this case the palladium(0)-catalyzed coupling with vinyl halides was found to be retentive. This finding is consistent with an inner-sphere transmetalation (Scheme 4 D).…”

Iterative reactions of transient boronic acids enable sequential C–C bond formation

“…1 The ability to form multiple C-C bonds using iterative or one-pot methods allows a rapid increase in molecular complexity. [2][3][4][5] While many such sequences are known, there is still room to exploit new reactivity patterns and different chemical combinations derived from reactive intermediates. 6 In recent times, transition metal chemistry has dominated C-C bond cross-coupling strategies.…”

Alkali metal mediated C–C bond coupling reaction

“…[1][2][3][4][5] Especially, the cross-coupling reactions have provided a great impetus to modern organic synthesis. According to the proposed mechanisms of these cross-coupling reactions, 6-10 the reaction is initiated by the oxidative insertion of palladium (0) into a carbon-halogen bond of the aryl halide used as substrate and forming a palladium (II) intermediate.…”