Remote Functionalization of α,β-Unsaturated Carbonyls by Multimetallic Sequential Catalysis

Abstract

The remote functionalization of α,β-unsaturated carbonyls by an array of multimetallic sequential catalytic systems is described. The reactions are triggered by hydrometalation using [Pd−H] or [Ru−H] isomerization catalysts and driven by the formation of thermodynamically more stable 1,2-vinyl arenes. The Pd-catalyzed deconjugative isomerization was combined with a Cu-catalyzed β-borylation of the transiently generated styrenyl derivatives to deliver a range of products that would not be accessible with the use of a single catalyst. [Pd/Cu] catalytic systems were also identified for the highly enantioselective α-hydroboration and α-hydroamination of the styrenyl intermediates. Difunctionalization simultaneously at the benzylic and homobenzylic positions was achieved by combining the isomerization process with Sharpless asymmetric dihydroxylation (SAD) using [Pd/Os] or [Ru/Os] couples. Starting from a simple α,β-unsaturated ester, an isomerization/ dihydroxylation/lactonization sequence gave access to a naturally occurring γ-butyrolactone in good yield, with excellent diastereo-and enantioselectivity.

Transition metal-catalyzed alkene isomerization as an enabling technology in tandem, sequential and domino processes

“…A series of remote functionalizations based on sequential multimetallic catalytic reactions has been reported by Mazet and co-workers. 35 The reactions are triggered by hydrometalation of a,b-unsaturated esters using [Pd-H] or [Ru-H] isomerization catalysts and are driven by the formation of thermodynamically more stable (hetero)vinyl arenes ( Fig. 9).…”

“…While tandem and domino reactions involving enol ethers occur preferentially intramolecularly, intermolecular transformations have been achieved by sequential multi-catalysis. Romano and Mazet identified conditions for the one-pot multimetallic conversion of allyl methylethers (34) in alkenes (35) with high degree of stereocontrol (Fig. 14).…”

Types and Distribution of Bioactive Polyunsaturated Aldehydes in a Gradient from Mesotrophic to Oligotrophic Waters in the Alborán Sea (Western Mediterranean)

“…Type I isomers of dC7, dC8, and dC10 were stable for 10 days in abiotic natural seawater at constant temperatures of 10, 15, and 20 • C in closed agitated systems [56], although the concentration of dC7 and dC8 decreased significantly compared with dC10. In nature, a physical isomerization via photodegradation or trace metal-mediated transformation [58] from Type I to Type II should be considered as a plausible explanation. In our dataset, no correlation was established between the percentage of abundance of Type II isomers and light intensity for any site, although trace metals were not quantified.…”

Earth-Abundant 3d Transition Metal Catalysts for Hydroalkoxylation and Hydroamination of Unactivated Alkenes

“…It has also been applicable to the preparation of various enantioenriched secondary (aryl)amines and amides and primary amines with high efficiency via structural alteration of the amine transfer agent and optimization of the reaction conditions (Figure 27). The use of the electron-rich ester p-NMe 2 C 6 H 4 CO 2 NHR 3 [168,169], 1,2-benzisoxazole [170] and substituted 2,1-benzisoxazoles [171] as modified electrophilic amine partners gives straightforward access to secondary amines, primary amines and secondary arylamines tethered to a benzylic alcohol respectively in moderate-to-good yields and high enantioinduction. For the reaction with benzisoxazole derivatives, a work-up is needed to liberate the amine functionality.…”