1-Hydroxyindoles rearrangement

In 1991, we proposed in our 1-Hydroxyindole Hypotheses (91YGK205) that some types of 1-hydroxyindoles (117) would undergo a rearrangement reaetion to provide 2-oxindole 118 and/or 3-oxindole 119 as illustrated in Seheme 18. As suitable substrates for realizing the predietions, we have sueeeeded in finding l,2,3,4-tetrahydro-9-hydroxy-/3-earboline eompounds 11 and 16a. 

On route to the Erythrina alkaloid 3-dimethoxyerythratidinone, Wang and Padwa encountered the interesting acid catalyzed rearrangement of lactam 151 to the tetracyclic hydroxyindole 153 via the lactone 152 <060L601>. 

The synthesis of 3- and 7-substituted indoles (184 and 185) by [3,3]-sigmatropic rearrangement of A-hydroxyindole derivatives (181) was reported (equation 54). A-hydroxyindole 181 in the presence of cyanogen bromide (182, R = Br, = N) and base afforded 183 that rearranged to the NCO substituted at position 3 and position 7, leading to two isomeric isocyanates, 184 and 185, respectively. Different behaviour was found when an acetylenic sulfone 182, R =11, R = CTos, was used where the 3-substituted indole 186 was the only rearrangement product identified. 

Quinoline 1-oxides can be rearranged photochemically into indoles (103 — 104 — 105) or N-hydroxyindoles (106 — 107). Cinnolines are reductively ring-contracted into indoles (Section 3.2.1.6.9.ii). 

The chlorosulfonium compounds can also be used for the synthesis of oxindoles, the stable tautomeric form of 2-hydroxyindoles. The a -methylthio ketone is replaced by ethyl methylthioacetate and the products of the Sommelet-Hauser rearrangement are cyclized to 3-methylthiooxindoles. The methylthiooxindoles are reductively desulfurized with Raney nickel (equation 102) (74JA5508). 

The reactions of the methyl furo[2,3-6]pyrrole-5-carboxylate (153) or its 6-methyl derivative (154) with DMAD proceed via [4 -I- 2] cycloaddition at the a,a -positions of the furan ring, giving cycloadducts which by subsequent 1,5-sigmatropic rearrangement give trimethyl 5-hydroxyindole-2,6,7-tricarboxylate (155) or its 1-methyl derivative (156) <94UP 70i-0i>. 

The photo-Fries rearrangement of 5- and 6-acetoxyindoles has been studied. Although mixtures of products are obtained, the major products are the 4-acetyl-5-hydroxyindole and the 7-acetyl-6-hydroxyindole, respectively <89TL6483>. 

In a series of papers, Kucklander has provided additional evidence for the Nenitzescu-Allen mechanism, in particular theD->-E- F- G transformation [18-20]. Eor example, isolated carbinolamine 35 gives byproducts 36-38 in addition to indole 39 (Scheme 7, equation 1) [18]. The formation of 36 presumably involves reaction of iminium ion 40 with acetate and rearrangement of 41 to 36 as shown (Scheme 7, eqnation 2) [20], Kucklander and Hiihnermann found that benzoquinone reacts with p-arylaminocrotonates in propionic acid to afford 6-hydroxyindoles 42 (10%-30%) (equation 3), along with the byproducts 5-acyloxy-4-hydroxyindoles (20%-35%) and arylaminobenzofurans (10%-15%) [21]. 

Scheme 6, equation 2) [12], The key step in Clive s sequence is the Hoftnann rearrangement of amide 17 to amine 18, followed by oxidation to quinone 19 with phenyliodme(ni) bis(triacetate). In like fashion, 4-bromo-5-hydroxyindole, 5-hydroxy-4-iodoindole, and 5-hydroxy-4-iodo-3-methylindole were prepared in this study. Nishiyama and coworkers adopted an electrochemical oxidation of diaryl amides to carbazoles (equation 3 and 21-22) [13]. 

Several investigators discovered the photochemical rearrangement of quinoline Af-oxides to the corresponding benzoxazepines and then to indoles. For example, Kobayashi and colleagues synthesized for the first time 2- and 3-trifluoromethylindoles via this route (Scheme 15, equation 1) [104]. In a series of papers, Kaneko and coworkers described the photochemical synthesis of indoles from quinoline Af-oxides via benzoxazepines, which were not isolated (equation 2) [105-109]. A similar photolysis of 5-(alkoxycarbonylamino)isoquinoline 2-oxides afforded l-alkoxycarbonyl-4-hydroxyindoles (equation 3) [110]. Irvine s group reported similar photochemical syntheses of indoles from quinoline Af-oxides albeit in low yields [111]. 

Treatment of 3-(3 -methyl-2-oxobutyl>3-hydroxyindole with thionyl chloride gave, unexpectedly, the thiolan derivative (29), and reduction of tra f-4-phenyl-but-3-en-2-one with sulphurated sodium borohydride gave 3-acetyl-2,6-diphenyl-4-hydroxy-4-methylthian, of unknown configuration. The cis- and /runr-isomers of 2-mercaptothiolan-2,5-dicar-boxylic acid were formed by base-catalysed rearrangement of 1,2-dithian-3,6-dicarboxylic acid. Unexceptional methods were used to synthesize various thiosugar derivatives, and the synthesis of a-methylbiotin, a new natural product, by a modification of the Hofman-LaRoche method has been described. ... 

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