We have developed a new methodology for the formation of fully substituted oxazoles through highly regioselective gold-catalysed cycloaddition.[1] This approach is fast and convergent in comparison to classic methods for the preparation of trisubstituted oxazoles.[2] All-carbon 2,4,5-substituted oxazoles are accessed via a novel gold-catalysed intermolecular formal [3+2]-cycloaddition across the p-system of internal alkynes (1   and 2  ) by employing conjugated N-ylides (3  ) as N-nucleophilic 1,3-N,O-dipole equivalents.[3]By employing electron-rich aryl/heteroaryl groups, comprising of indole (1  ) and aniline derivatives (2  ), highly regioselective C-C p-system activation can be efficiently achieved. This intermolecular addition to an unsymmetrical internal alkyne represents a considerable regioselectivity and reactivity challenge; there are no examples of intermolecular atom-transfer nitrene addition by p-acid activation of an internal alkyne. Moreover, this 3-indole oxazole motif is found in pimprinine derivatives and provides potentially interesting framework of organic materials and medicinal compounds.[4] This presentation shows the development of the catalytic cycloaddition, the substrate scope, the study into the regiocontrol factors and further applications of the final products.[1] E. Chatzopoulou and P. W. Davies, Chem. Commun., 2013, 49 , 8617.[2] K. Murai, Y. Takahara, T. Matsushita, H. Komatsu and H. Fujioka, Org. Lett., 2010, 12 , 3456.[3] P. W. Davies, A. Cremonesi and L. Dumitrescu, Angew. Chem. Int. Ed., 2011, 50 , 8931.[4] J. R. Davies, P. D. Kane, C. J. Moody and A. M. Z. Slawin; J. Org. Chem., 2005, 70  , 5840.

Highly regioselective synthesis of fully substituted oxazoles by intermolecular reaction of unsymmetrical internal alkynes

248th National Meeting (2014)

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