syn-Selective alkylarylation of terminal alkynes via the combination of photoredox and nickel catalysis

Abstract

Substituted alkenes are pivotal structural motifs found in pharmaceuticals and agrochemicals. Although numerous methods have been developed to construct substituted alkenes, a generally efficient, mild, catalytic platform for the conversion of alkynes to this highly functionalized scaffold via successive C-C bond forming steps remains in high demand. Here we describe an intermolecular, regio- and syn-stereoselective alkylarylation of terminal alkynes with tertiary alkyl oxalates via photoredox-Ni dual catalysis. This catalytic protocol, synergistically combining Ir/Ni-catalyzed alkyne difunctionalization with photoinduced alkene isomerization, affords trisubstituted alkenes with excellent efficiency and syn-stereoselectivity. The mild conditions tolerate many functional groups, allowing for a broad scope with respect to terminal alkynes, aryl bromides, and alkyl oxalates.

Fig. 1

syn-Alkylarylation of terminal alkynes via the combination of photoredox and nickel catalysis. a Alkyne functionalizations via transition metal catalysis. b syn-Alkylarylation of alkynes via metallaphotoredox catalysis

Fig. 2

Proposed mechanism. Two possible reaction pathways proposed on the basis of previous literature

Fig. 3

Substrate scope. a Scope of alkynes. b Scope of cesium oxalates. c Scope of aryl halides. Reaction conditions: Ir-1 (3 mol%), NiCl₂•glyme (20 mol%), dtbbpy (20 mol%), alkyne (0.1 mmol), oxalate (1.5 equiv.), bromide (2.0 equiv.), DMSO [0.05 M], 90 W blue LED, 36 °C, 18 h. All cited yields are isolated yields. The ratios of the two isomers were determined by ¹H NMR analysis of the crude reaction mixtures. ^aHeteroaryl chloride was employed. dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl

Fig. 4

Reaction on large scale. Reaction condition: Ir-1 (3 mol%), NiCl₂•glyme (20 mol%), dtbbpy (20 mol%), alkyne (4 mmol), oxalate (1.5 equiv.), bromide (2.0 equiv.), DMSO [0.05 M], 90 W blue LED, 36 °C, 18 h. Isolated yield. The ratio of the two isomers were determined by ¹H NMR analysis of the crude reaction mixture. dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl

Fig. 5

Mechanistic studies. a Time course studies; b UV–Vis absorption spectrometry; c Isomerization experiments; d Reaction of alkyne with oxalate; e Stoichiometric reaction of isolated Ni(II) complex. dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl