Ruthenium–Hydride Complexes Facilitated Sustainable Synthesis of Isoxazolones via Acceptorless Dehydrogenative Annulation of Alcohols

Abstract

A streamlined strategy for the one-pot synthesis of isoxazolone analogues has been developed through an acceptorless dehydrogenative annulation (ADA) pathway by employing new Ru(II) hydride complexes as effective catalysts. New Ru(II) complexes (C1–C3) tailored with N̂O chelating carbazolone benzhydrazone ligands were synthesized and their formation was confirmed using analytical and spectral techniques including FT-IR and NMR. The structural configuration of the complexes featuring an octahedral geometry around the Ru(II) ion was precisely determined by single-crystal X-ray diffraction analysis. Further, the catalytic efficacy of the titled complexes has been established for the facile and productive synthesis of isoxazolone derivatives from a diverse range of benzyl alcohols, methyl acetoacetate/ethyl benzoylacetate and hydroxylamine hydrochloride, generating excellent yields of up to 93% under well-suited mild conditions with 1 mol % of catalyst loading. A sequence of time-dependent control experiments unveiled the ADA route, indicating the initial generation of an 4-methoxy benzaldehyde intermediate followed by 3-phenylisoxazol-5(4H)-one, accompanied by the release of water and hydrogen as byproducts. Gram-scale synthesis of the compound indicates the industrial relevance of our synthetic strategy. A short synthesis of medicinally active androgen antagonist illustrates the utility of the present protocol.