Preparation and Chemistry of 4-Coumarylzinc Bromide

General Procedure for Pd-Catalyzed Cross-Coupling Reactions 

Since the heterocyclic moiety found in many natural compounds plays a critical role for biological activity, the next attempt was to couple 1 with several heteroaryl acid chlorides. Table 3.28 illustrates the reaction conditions and the results. Once again, it should be emphasized that all the coupling reactions were carried out under mild conditions. 5-Bromonicotinoyl chloride and 6-chloronicotinoyl chloride were efficiently employed for the coupling reaction 

The coupling reaction with 2-bromopyridine also proceeded well to generate 3h in good yield (Table 3.29, entry 8). 

In conclusion, a novel synthetic route for the preparation of 4-substituted cou-marin derivatives has been demonstrated. It has been accomplished by utilizing a simple coupling reaction of a readily available 4-coumarinylzinc bromide (I), which was prepared via the direct insertion of active zinc to 4-bromocoumarin. The subsequent coupling reactions with a variety of different electrophiles have been carried out under mild conditions, providing a new class of 4-substituted coumarins. 

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