Sommelet-Hauser rearrangement synthesis

Another indole/oxindole synthesis achieves the critical ortho-substitution by Sommelet-Hauser rearrangement of an anilinosiilfonium ion intermediate. Use of P-thioketones (G = R, an alkyl group) generates 2-substituted indoles, whereas P-thioesters (G = OR) lead to oxindoles. In each case, a 3-thio substituent must be removed by desulfuri2ation. 

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). 

An illustration of the Sommelet-Hauser rearrangement is the synthesis of 2-methyl-2,3,4,5,6,7-hexahydro-lH-2-benzazonine from 2-phenyl-l-[(trimethylsilyl)methyl]-piperidine in good yield, where a stable trienic intermediate aromatized only after treatment with base for 24 h at room temperature.369... 

The Sommelet-Hauser rearrangement has rarely been used as a tool in organic synthesis and then only for very special systems [54], The reason is undoubtedly that the Hofmann elimination and the dealkylation reaction of quaternary nitrogen atoms are in direct competition with the ring expansion reactions of these substrates. 

Nakano, M., Sato, Y. A convenient synthesis of o-methylbenzylamlne derivatives from benzyl halides the improved Sommelet-Hauser rearrangement. J. Chem. Soc., Chem. Commun. 1985, 1684-1685. 

The mechanism of the Gassman indole synthesis bears some resemblance to that of the Fischer indole reaction. An Sn2 displacement of the TV-chlorinated aniline with the a-keto sulfide gives rise to a sulfonium ion. After deprotonation, a [2,3]-sigmatropic rearrangement (Sommelet-Hauser rearrangement) takes place where the weak N-S bond is broken and a strong C-C bond is formed. Similar to the Fischer indole reaction, the resulting imine was transformed into indole after re-aromatization and cyclization. 

Sommelet-Hauser rearrangement in indole synthesis Gassman indole synthesis... 

Several variations exist for the classic Sommelet-Hauser rearrangement. The most important concern the use of base-free conditions for the [2,3]-sigmatropic rearrangement based on the fluoride anion induced desilylation of substituted benzyldialkyl-[(trimethylsilyl)methyl] ammonium halides" and the asymmetric versions of Sommelet-Hauser rearrangement that appeared recently in the literature. None of the above has ever been used in a modification of the Gassman indole synthesis. 

Although nitrogen ylides have been extensively used in organic transformations, especially those concerning the formation of nitrogen heterocycles,not many references are available for the use aza-sulfonium ylides and the Sommelet-Hauser rearrangement in the synthesis of indole derivatives. 

In 1981, Wierenga first introduced a modification of Gassman oxindole synthesis for the synthesis of indole derivative 34, part of the left-hand segment of the antitumor agent CC-1065. In accordance to that, addition of derivative 30 in a equimolar amount of the hindered base, [1,8-bis(dimethylamino)naphthylene (R3N), to the chloride complex of ethyl-a-(mercaptomethyl)propionate 31, followed by a triethylamine catalyzed Sommelet-Hauser rearrangement and an acid-induced cyclization gave oxindole 32. Treatment of 32 with excess BH3 SMei at room temperature afforded 33 in 95% yield. 

In 2003, Alper and co-workers, based on an earlier, reported the synthesis of substituted tosyl-indoles from substituted anilines and isopropylsulfides, introduced a practieal way for the elaboration of multigram scale of the otherwise difficult accessible methyl 7-chloroindole-4-carboxylate, based on the desulfurization and cyclization of a prior Sommelet-Hauser rearranged produet 41, derived from the reaction of methylsulfide 39 with o-chloroaniline derivative 40. 

Methods development for ring contractions generating enediynes H. Audrain etal. Tetrahedron 50,1469 (1994). Review of stereoselectivity K. Mikami, T. Nakai, Synthesis 1994, 594. Reviews J. A. Marshall, Comp. Org. Syn. 3, 975-1014 (1991) T. Nakai, K. Mikami, Org. React. 46,105-209 (1994). Cf. Meisenheimer Rearrangements Mislow-Evans Rearrangement Sommelet-Hauser Rearrangement. 

Catalytic thia-Sommelet-Hauser rearrangement toward the synthesis of oxindoles... 

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