Jones indole synthesis

Construction of the Dolby model system began with epoxidation of cyclohexene 209 employing mCPBA in chloroform. The epoxide product was then subjected to a base-promoted cyclization via amide deprotonation and oxirane opening to provide benzamide 210 (Scheme 23). Hydroxyl oxidation using the Jones conditions next furnished cyclohexanone 211. A Fischer indole synthesis on this scaffold, followed by amine deprotection using sodium hydroxide, led to the desired l,3-(iminoethano)carbazole 83. While the yield of this route was low, it was the first example of a method to fashion the 2-azabicyclo[3.3.1]nonan-8-one system 211, and importantly demonstrated that indoHzation on such a scaffold was possible. 

An important variation of the Jones-Schmid indole synthesis is the base-mediated cyclization onto esters, which affords 3-hydroxyindoles (indoxyl tautomers) under mild conditions. Three case studies are shown in Scheme 2 (equations 1-3) [18-20]. This chemistry, like that in Table 1 (Entries 4-11), represents a powerful route to C-3 functionalized indoles. Kraus and coworkers use the steri-cally hindered phosphazine base, P -t-Bu, to prepare the 5,6-dihydroindolo[2,l-a]isoquinoline ring system (equation 4) [21]. Several derivatives display immunosuppressive activity. 

Scheme 2 Variations of the Jones-Schmid Indole Synthesis...

Jones and co-workers reported the ruthenium-catalyzed synthesis of indol derivatives in a single step starting from di-o,o -substituted aromatic isonitriles a representative example is shown in Scheme 77 366>366a... 

Another type of unique coupling reaction was reported by Jones and coworkers [87]. The low-valent ruthenium phosphine complexRuH2(dmpe)2 catalyzed intramolecular insertion of isocyanide into the benzyl C-H bond of 2,6-xy-lylisonitrile under thermal conditions (Eq. 59). Their finding provided a new route to the synthesis of indoles. 

Jones also reported the synthesis of hydroxyazepinoindolium 269 (68TL1935). -Substituted indole 265 was cyclized to yield ketone 266. Ketone 266 was reacted with perbromide to give dibromoketone 267, which was treated with lithium chloride in DMF to yield 268. Ketone 268 was converted to 269 by addition of acid. 

Jones conditions), aqueous acid, and mild Lewis acids.The Boc group is usually removed by treatment with aqueous HCll or with anhydrous trifluoroacetic acid. In Lai s synthesis of indole analogs of mycophenolic acid, indole derivative 143 was converted to the N-Boc compound (144) using Boc anhydride. Elaboration of the side chain in three steps was followed by deprotection with HCl in dioxane, giving 145 in 72% yield. Trifluoroacetic acid in dichloromethane converted 145 to 146 in 60% yield. 

Jones GB, Moody CJ (1989) Structurally modified antitumor agents. Part 1. Synthesis of cyclopropapyrrolo[l,2-a]indoles related to mitosenes by intramolecular cycloaddition. J Chem Soc Perkin Trans 1 2449-2454... 

The synthesis of l,2-cyclopropapyrrolo[l,2-a]indoles devised by Moody and Jones [54] was based on 1,3-dipolar addition of a diazo group to an alkene (Scheme 24). In this synthesis, indole-2-carboxaldehyde 169 was alkylated with allyl bromide in the presence of sodium hydride and then condensed with tosylhydrazine to give 170. The sodium salt of 170 underwent [3 + 2] cycloaddition, affording 171, when it was heated in benzene. Further heating in refluxing... 

Several reviews on the synthesis and the chemistry of indoles have been published D.J. Chadwick, R.A. Jones,... 

Price-Jones, M.J. and Harwood, J. L. (1983) Hormonal regulation of phosphatidylcholine synthesis in plants. The inhibition of cytidylyltransferase activity by indol-3-ylacetic acid, Biochem. J. 216, 627-631. 

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