Baeyer Oxindole Synthesis

The invention of the triflate (trifluoromethylsulfonyl) group — one of the world s best leaving groups — has led to its use in palladium chemistry [42]. Conway and Gribble described the synthesis of 3-indolyl triflate 34 [12] and 2-indolyl triflate 35 from oxindole [43]. Mdrour synthesized the N-phenylsulfonyl derivative 36 by employing a Baeyer-Villiger oxidation of the appropriate indolecarboxaldehyde [44],... 

In most indigo syntheses the indole structure is built up by ring closure of appropriate benzene derivatives by C-N or C-C bond formation. Examples of C-N bond formation include von Baeyer s 1878 synthesis from phenylacetic acid (3) via oxindole (4). 

The easy condensation of aldehydes with 3-monosubstituted oxindoles has been further exploited by Ban and co-workers, who synthesized several 3-spirooxindole derivatives 48). The approach was used in the stereospecific synthesis of racemic iV-methylrhynchophyllane (Chart X). The Iraws-diethylcyclopentanone CVIIIa was subjected to Baeyer-Villiger oxidation to yield the threo lactone CIX, which was converted to the chloroaldehyde CXI, by successive reaction with phosphorus... 

This reaction was first reported by von Baeyer in 1878. It is the synthesis of oxindole via the acidic reduction of o-nitrophenylacetic acid by tin and the subsequent cyclization of the resulting reduced intermediate. Besides such reaction conditions, other acidic reducing combinations can also be applied to the preparation of oxindole, including Zn + H2SO4, Zn + HOAc, and Fe + HOAc, SnCl2 + NH4CI. Recently, other methods have been developed for preparing oxindoles. ... 

Baeyer confirmed his results by the total synthesis of oxindole, isatin and indole. Nitration ofphenylacetic acid, isolation of the o-nitro isomer, and reduction of the latter followed by ring closure gave oxindole. Reaction with nitrous acid ( .e. potassium nitrate and sulfuric acid) gave isatin oxime, from which by reduction, dehydrogenation with iron(lll) chloride and final hydrolysis, isatin itself was obtained. 

The leading figure in the discovery and early chemistry of indole is Adolf Baeyer, who first synthesized indole by heating oxindole with zinc powder [1] and by reducing 2,3-dichloroindole with zinc/KOH [2], For an excellent review of the early indole chemistry, see Sumpter and Miller [3], Given Baeyer s seminal history with indole, it was fitting that he and Jackson discovered in 1880 the first practical synthesis of indoles the Baeyer-Jackson indole synthesis (Scheme 1, equation 1) [4, 5], which entails the reductive cyclization of o-nitrobenzyl carbonyl compounds. Since 1880, this simple indolization has been used extensively, as seen both in this chapter and in previous chapters. Scheme 1 includes some additional early indole syntheses of this type (equations 2-4) [6-8]. For a discussion of the early syntheses of indoloindoles (cf. equation 4), see Samsoniya and Trapaidze [9]. 

Baeyer s most famous researches, on the constitution and synthesis of indigo, began in 1865. Indigo had been investigated by Laurent and by Erdmann, who obtained isatin from it by oxidation (see p. 389). Baeyer showed that isatin on reduction forms dioxindole and then oxindole, which when distilled with zinc dust (a favourite method with Baeyer) is reduced to the parent substance indole ... 

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