Catalytic conjunctive cross-coupling enabled by metal-induced metallate rearrangement

Abstract

Transition metal catalysis plays a central role in contemporary organic synthesis. Considering the tremendously broad array of transition metal-catalyzed transformations, it is remarkable that the underlying elementary reaction steps are relatively few in number. Here, we describe an alternative to the organometallic transmetallation step that is common in many metal-catalyzed reactions, such as Suzuki-Miyaura coupling. Specifically, we demonstrate that vinyl boronic ester ate complexes, prepared by combining organoboronates and organolithium reagents, engage in palladium-induced metallate rearrangement wherein 1,2-migration of an alkyl or aryl group from boron to the vinyl α-carbon occurs concomitantly with C-Pd σ-bond formation. This elementary reaction enables a powerful cross-coupling reaction in which a chiral Pd catalyst merges three simple starting materials-an organolithium, an organoboronic ester, and an organotriflate-into chiral organoboronic esters with high enantioselectivity.

Fig. 1. Metal-induced metallate shift as a strategy for catalytic reaction design

(A) The catalytic conjunctive cross-coupling process. (B) Common metallate shift to saturated carbon centers requires a leaving group. (C) Metallate shift to unsaturated carbons often is activated by addition of an external electrophile. (D) A metallate shift promoted by a metal complex can serve as an alternative to a transmetallation process. (E) Proposed catalytic cycle for conjunctive cross-coupling.

Fig. 2. Scope of the catalytic conjunctive cross-coupling reaction starting from vinyl boronic esters

Yields represent isolated yield of purified material and are an average of two experiments. The absolute configuration was determined by anomalous dispersion x-ray and by chromatographic comparison to known compounds. *VinylB(neo) was replaced with vinylB(pin); †Reaction conducted at 80 ° C. er (enantiomeric ratio) was determined by chiral supercritical fluid chromatography.

Fig. 3. Scope of the catalytic conjunctive cross-coupling reaction starting from alkyl or aryl boronic esters

Yields represent isolated yield of purified material and are an average of two experiments.

Fig. 4. Synthesis and mechanistic studies

(A) Synthesis of combretastain by conjunctive cross-coupling. (B) The stereochemical course of metal-induced metallate rearrangement.