Application of radical cross-dehydrogenative coupling (CDC) procedures to prepare a range of novel spirocyclic oxindoles and to a formal total synthesis of the vasopressin V2 receptor antagonist ...Satavaptan is reported. The key step involves a copper-mediated oxidative cyclisation of a simple linear anilide precursor to give the spirocyclic oxindole core. This synthetic approach was also used to prepare novel Satavaptan scaffolds and analogues.
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A double C–H, Ar–H coupling process for the conversion of bis-anilides into spirocyclic bis-oxindoles, enabling the concomitant formation of two all-carbon quaternary centers at oxindole 3-positions ...in a diastereoselective manner, is described. The optimum cyclization conditions utilize stoichiometric Cu(OAc)2·H2O/KOtBu in DMF at 110 °C and have been applied to prepare a range of structurally diverse bis-spirooxindoles in fair to good yields (28–77%); the method has also been extended to prepare bis-oxindoles linked by a functionalized acyclic carbon chain.
The synthesis of bis-oxindoles via the copper(II)-mediated double cyclisation of linear bis-anilides is described. Cu(OAc)2·H2O was identified as an efficient and inexpensive catalyst for this ...process. In contrast to previous methods, which rely on the synthesis of the central core from existing oxindole building blocks, this new approach focusses on concurrent formation of both oxindole rings from a simple linear precursor, allowing the formation of bis-oxindoles containing a diverse range of cyclic and acyclic linkers using a single synthetic method.
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A copper(II)‐catalysed approach to oxindoles, thio‐oxindoles, 3,4‐dihydro‐1H‐quinolin‐2‐ones, and 1,2,3,4‐tetrahydroquinolines via formal CH, ArH coupling is described. In a new variant, copper(II) ...2‐ethylhexanoate has been identified as an inexpensive and efficient catalyst for this transformation, which utilises atmospheric oxygen as the re‐oxidant.
Copper(II) 2‐ethylhexanoate: The synthesis of oxindoles, thio‐oxindoles, 3,4‐dihydro‐1H‐quinolin‐2‐ones, and 1,2,3,4‐tetrahydroquinolines from linear precursors by direct CH, ArH coupling by using a single copper catalyst is reported (see scheme; DIPEA=diisopropylethylamine, EWG=electron‐withdrawing group). The cyclisations are simple to perform, run open to the air, are moisture insensitive, and use an inexpensive catalyst.
Abstract
A facile copper(II)‐mediated C–H bond oxidation and C–C bond formation procedure has been applied to the synthesis of indole derivatives. Intramolecular oxidative coupling of ...3,3‐disubstituted enamines proceeded using a non‐expensive and air‐stable copper salt, Cu(2‐ethylhexanoate)
2
, to afford the corresponding C‐3 quaternary indolenine products in good to excellent yields. 1
H
‐Indoles can be prepared in a similar manner but in this case, Cu(OAc)
2
·
H
2
O has been found to be the preferred oxidant.
A facile copper(II)‐mediated C–H bond oxidation and C–C bond formation procedure has been applied to the synthesis of indole derivatives. Intramolecular oxidative coupling of 3,3‐disubstituted ...enamines proceeded using a non‐expensive and air‐stable copper salt, Cu(2‐ethylhexanoate)2, to afford the corresponding C‐3 quaternary indolenine products in good to excellent yields. 1H‐Indoles can be prepared in a similar manner but in this case, Cu(OAc)2·H2O has been found to be the preferred oxidant.
An efficient copper‐mediated oxidative coupling approach for the cyclisation of linear enamines to indole derivatives is described. The transformation can be efficiently carried out using inexpensive copper(II) salts.
A practical and efficient entry to spirocyclic oxindoles from readily accessible anilide precursors, using only catalytic amounts of an inexpensive copper salt together with air as the sole ...re-oxidant, is described. In addition to providing access to a broad range of spiro-oxindole products, the utility of this method is demonstrated in a formal synthesis of the natural product, horsfiline.
A copper(II)-catalysed approach to oxindoles, thio-oxindoles, 3,4-dihydro-1H-quinolin-2-ones, and 1,2,3,4-tetrahydroquinolines via formal CH, ArH coupling is described. In a new variant, copper(II) ...2-ethylhexanoate has been identified as an inexpensive and efficient catalyst for this transformation, which utilises atmospheric oxygen as the re-oxidant.
Nitrogen-containing heterocycles have attracted considerable attention owing to their prevalence in numerous natural substances as well as their extensive applications in biology and pharmacology. In ...recent years, great efforts have been devoted to the elaboration of novel synthetic methodologies for the construction of N-heterocycles such as oxindoles and indoles. Reported in 2009 by the Taylor group, access to oxindole scaffolds has been successfully demonstrated via a copper(II)-mediated oxidative coupling approach. Following the same principle, the extension of this method to the formation of the more intricate bis-oxindole skeleton is demonstrated via the double cyclisation of bis-anilides using Cu(OAc)2·H2O as oxidant. The scope of the copper(II)-mediated cyclisation to the formation of 3H-indoles and 1H-indoles from N-aryl enamines is also described. Progress towards the total synthesis of the highly complex spirooxindole alkaloid natural product rankinidine is presented. Towards this end, the application of the copper(II)-mediated cyclisation for the formation of the oxindole core of rankinidine is presented.
Nitrogen-containing heterocycles have attracted considerable attention owing to their prevalence in numerous natural substances as well as their extensive applications in biology and pharmacology. In ...recent years, great efforts have been devoted to the elaboration of novel synthetic methodologies for the construction of N-heterocycles such as oxindoles and indoles. Reported in 2009 by the Taylor group, access to oxindole scaffolds has been successfully demonstrated via a copper(II)-mediated oxidative coupling approach. Following the same principle, the extension of this method to the formation of the more intricate bis-oxindole skeleton is demonstrated via the double cyclisation of bis-anilides using Cu(OAc)2·H2O as oxidant. The scope of the copper(II)-mediated cyclisation to the formation of 3H-indoles and 1H-indoles from N-aryl enamines is also described. Progress towards the total synthesis of the highly complex spirooxindole alkaloid natural product rankinidine is presented. Towards this end, the application of the copper(II)-mediated cyclisation for the formation of the oxindole core of rankinidine is presented.
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