A general study on selective functionalization of unsubstituted oxazole is reported.
Specific halogenation at C2 and C5 was enabled by a sequential deprotonation strategy
that was based on the different pK
a values of these positions, while a halide at C4 may be introduced by an optimized
halogen dance reaction. Efficient protocols for subsequent sp2–sp2 and sp2–sp3 cross-coupling reactions of the derived oxazolyl halides were then established. This
modular approach was applied in the total synthesis of ajudazol A and a selected analogue,
demonstrating the general feasibility of these conditions in a complex setting.
Key words
oxazole - halogen dance reaction - halogenation - Negishi/ Suzuki cross-coupling -
ajudazol A