2-zincated oxazole

Zinc Derivatives Oxazoles and benzoxazoles can be lithiated in the 2-position by alkyllithium. In transmetallation of lithiated oxazole excess zinc dichloride gave the highest yield. The zincated substrates 106 and 107 were used in Negishi-type coupling (Scheme 45). Reactions of zincated oxazoles and benzoxazole with aryl halides all proceed well. A similar reaction sequence was used in the preparation of a 2-oxazolyl-substituted tricyclic structure 108. 

The Negishi coupling allows also the coupling of zincated oxazoles in very good yields (Scheme 5-71). This reaction was optimized to be conducted on larger scale, since this and related products formed are important intermediates in the synthesis of an active pharmaceutical ingredient (API). 

Zinc Derivatives Oxazole and 5-substituted oxazoles are lithiated in the 2-position. Subsequent zincation gives the corresponding 2-oxazolylzinc chloride 112 for alkenylation (Scheme 48). Excess of zinc chloride was used in the zincation. Subsequent cross-coupling with a 1-butenyl iodide yields 2-alkenyl derivatives. The Pd-catalyst was pregenerated by reduction with DlBALH.t The alkenylated oxazole 113 was formed in a corresponding coupling reaction with a cyclic vinyl triflate. ... 

Further elaborations/modifications of the oxazole ring were also described. For example, a new POCN-pincer palladium catalyst was used in the copper-mediated arylation of the C-2 position of benzoxazoles and oxazoles with aryl iodides in satisfactory yields (14DT16084). An original method for the direct amination of heteroarenes including benzoxazoles was reported involving a one-pot heteroarene C-H zincation followed by a copper catalyzed electrophilic amination (14AGE4667). 

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