A Dual Palladium and Copper Hydride Catalyzed Approach for Alkyl-Aryl Cross-Coupling of Aryl Halides and Olefins

Abstract

We report an efficient means of sp² -sp³ cross coupling for a variety of terminal monosubstituted olefins with aryl electrophiles using Pd and CuH catalysis. In addition to its applicability to a range of aryl bromide substrates, this process was also suitable for electron-deficient aryl chlorides, furnishing higher yields than the corresponding aryl bromides in these cases. The optimized protocol does not require the use of a glovebox and employs air-stable Cu and Pd complexes as precatalysts. A reaction on 10 mmol scale further highlighted the practical utility of this protocol. Employing a similar protocol, a series of cyclic alkenes were also examined. Cyclopentene was shown to undergo efficient coupling under these conditions. Lastly, deuterium-labeling studies indicate that deuterium scrambling does not take place in this sp² -sp³ cross coupling, implying that β-hydride elimination is not a significant process in this transformation.

Keywords: alkenes; copper; cross-coupling; homogeneous catalysis; palladium.

Scheme 1

Pd- and CuH-catalyzed reductive cross coupling of terminal olefins with aryl electrophiles.

Scheme 2

Comparison of electron-deficient aryl chlorides and bromides in Pd/CuH-catalyzed reductive cross coupling reactions; A) Anti-Markovnikov reductive cross coupling with α-olefins; B) Enantioselective Markovnikov hydroarylation of vinylarenes. [a] All yields represent the average of isolated yields from two runs performed with 1 mmol of olefin. [b] Enantiomeric excess determined by chiral HPLC.

Scheme 3

Scale-up of the reductive cross coupling. Yields represent the average of isolated yields from two runs performed with 10 mmol of olefin.

Scheme 4

Investigation of cyclic alkenes as substrates in the Pd/CuH-catalyzed reductive cross-coupling. [a] Yield represents the average of isolated yields from two runs performed with 1 mmol of aryl bromide. [b] Yield determined by analysis of the crude reaction mixture via ¹H-NMR spectroscopy using 1,3-benzodioxole as an internal standard.

Scheme 5

Deuterium-labeling studies for the Pd/CuH-catalyzed reductive cross coupling of terminal alkenes with aryl bromides. Deuterium incorporation was quantified by ¹H-NMR spectroscopy of the purified products.