Ruthenium-Hydride Complexes Facilitated Sustainable Synthesis of Isoxazolones via Acceptorless Dehydrogenative...

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.