Copper-Catalyzed Synthesis of Benzoxazoles
SCHEME 1. Copper- and Palladium-Catalyzed Formation
of Benzimidazoles and Benzothiazolesa
SCHEME 2. General Approach to the Synthesis of
Substituted Benzoxazoles 7 from ortho-Haloanilines 5
tion.16,17 As part of our program in benzo-fused azole synthesis,
we became interested in whether a similar strategy employed
in the synthesis of 3 and 4 could be applied to the formation of
benzoxazoles 7 (Scheme 2). This approach would remove the
requirement for the use of 2-aminophenols as precursors to
benzoxazoles, instead utilizing 2-haloanilines 5, which are
readily available, for example, through electrophilic aromatic
substitution. Acylation of the 2-haloanilines 5 could then be
used to generate the ortho-haloanilide substrates 6 required for
the copper-catalyzed cyclization.
a (a) CuI (5 mol %), 1,10-Phen (10 mol %), Cs2CO3 (2 equiv), 80 °C,
DME, 16-24 h. (b) Pd(PPh3)4 (5-10 mol %), Cs2CO3 (2 equiv), 80 °C,
DME, 16-24 h.
In general, the use of copper catalysts proved superior to that
of palladium9 in these reactions. These results follow the recent
resurgence of copper-mediated reactions, beyond that of classical
Ullmann etherifications10,11 and aminations12,13 and Goldberg
amidation14,15 reactions, through the use of ligand accelera-
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