An Efficient Three-Component Synthesis of 3-(5-Alkyl/aryl-1,3,4-oxadiazol-2-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-ones

Abstract

An efficient three-component synthesis of 3-(1,3,4-oxadiazol-2-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-ones is described. A mixture of N-isocyaniminotriphenylphosphorane, an isatin, and a carboxylic acid undergoes a 1:1:1 addition reaction under mild conditions to afford the title compounds in excellent yields.

One Reacts as Two: Applications of N-Isocyaniminotriphenylphosphorane in Diversity-Oriented Synthesis

“…As shown in Scheme A, much emphasis has been put on the investigation of the oxo-component reactivity. The reaction works well with aliphatic and aromatic aldehydes but only with highly reactive ketones. ,,− As expected, ketones are less likely to interact with the sterically congested isonitrile partner and to react properly, they must be highly strained (e.g., cyclobutanone) or bear electron-deficient substituents (e.g., α-halo-ketones, , isatine, acenaphthoquinone, − α-acyloxy propanones, , and 1,2-diketones). ,,− The preferred solvents are DCM, chloroform, and acetonitrile, although water has been employed with good results in the pursuit of greener procedures. ,, The mild conditions and general applicability of this reaction recently led to medicinal applications, such as the screening of oxadiazole libraries, to seek antibacterial compounds . Thus, it was found that some oxadiazole derivatives containing a pyridine ring were fairly active against Staphylococcus aureus and Staphylococcus epidermidis .…”

“…The reaction works well with aliphatic and aromatic aldehydes but only with highly reactive ketones. 69,70,74−77 As expected, ketones are less likely to interact with the sterically congested isonitrile partner and to react properly, they must be highly strained (e.g., cyclobutanone) 78 or bear electron-deficient substituents (e.g., α-halo-ketones, 70,79 isatine, 73 acenaphthoquinone, 80−82 α-acyloxy propanones, 83,84 and 1,2-diketones). 71,72,85−87 The preferred solvents are DCM, chloroform, and acetonitrile, although water has been employed with good results in the pursuit of greener procedures.…”

“…Since then, many new publications have appeared studying the scope of the Passerini-3C/ aza -Wittig reaction. Previously described has been the use of substituted benzoic acids, heteroaryl and polycyclic aromatic carboxylic acids, and cinnamic acids, − while only one example of an aliphatic acid is known . As shown in Scheme A, much emphasis has been put on the investigation of the oxo-component reactivity.…”

Progress in Reactions of N‐Isocyanoiminotriphenylphosphorane

“…Later, they developed a 1:1:1 addition reaction of NIITP 1 , isatins 47 and acarboxylic acids 48 for the synthesis of 3‐(1,3,4‐oxadiazol‐2‐yl)‐3‐hydroxy‐1,3‐dihydro‐2 H ‐indol‐2‐ones 49 (Scheme ) …”

Isatin derivatives in reactions with phosphorus(III–V) compounds

“…102 The process included addition of isonitrile carbon atom to isatin and subsequent aza-Wittig reaction (Scheme 42).…”