Cobalt-Catalyzed Cross-Coupling Reactions of Heterocyclic Chlorides with Arylmagnesium Halides and of Polyfunctionalized Arylcopper Reagents with Aryl Bromides, Chlorides, Fluorides and Tosylates

Abstract

A range of aromatic organocopper or organomagnesium compounds undergo smooth cross-coupling reactions with aryl bromides, chlorides, fluorides and tosylates, leading to polyfunctionalized aromatics or heterocycles in the presence of cobalt salts (5-7.5 mol%) as catalysts. Very mild reaction conditions are needed and, in the case of cross-coupling with organocopper compounds, Bu₄NI (1 equiv) and 4-fluorostyrene (20 mol%) are essential as promoters for successful couplings.

Key words

cross-coupling - transition metals - magnesium - heterocycles - halides

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19

In the absence of the cobalt catalyst, full conversion (GC) was detected only after four days at room temperature.

21

Commercial cobalt powder was used (Aldrich, 99.9+% purity).

22

Commercial iron powder was used (Merck, ≥99.5% purity).

25

After 24 hours reaction time only 47% conversion was observed.

28

29% conversion was observed after four hours and 42% conversion after 21 hours reaction time at 80 °C.

29

Besides DMPU, NMP and N,N-dimethylacetamide (DMAC) also led to a rate acceleration, but DMPU showed the strongest effect.

33

Confirmed by HMBC-NMR analysis.

37

No full conversion was observed if only 1.7 or 2 equivalents of copper reagent were used. In the absence of the cobalt-catalyst, no product was detected even after two days.

38

A mixture of mono- and two-fold cross-coupling product was obtained if only three equivalents of the arylcopper reagents 5l or 5i was used.