Bartoli synthesis

From ortho-Substituted Nitro-Arenes Bartoli Synthesis... 

In the extraordinary, but nonetheless efhcient and extremely practically simple process now known as the Bartoli synthesis, ort/ < -substituted nitrobenzenes treated with three mole equivalents of vinylmag-nesium bromide give 7-substituted indoles. The process works best when the 7-substitutent is large (a bromine can be used as a removable Targe group ) and it is thought that initial attack by the vinyl... 

From ortho-substituted nitroarenes Bartoli synthesis... 

Dobbs has reported a short synthesis of several complex indoles (01JOC638). The radical reduction follows the Bartoli synthesis (89TL2129, 91JCS(P1)2757) of several indole derivatives and the following example is illustrative (Scheme 43). 

Following these early investigations on the Bartoli indole synthesis, several research groups made use of this reaction to great effect as a starting point in natural product synthesis despite the inherent low to modest yields. Stolz employed the Bartoli synthesis to prepare 7-benzyloxy-4-bromoindole (33% yield from 2-benzyloxy-5-bromoni-(robenzene and vinylmagnesium bromide) in the first total synthesis of the marine bis-indole ( )-dragmacidin D [24]. 

Even though the yields of indoles from the Bartoli synthesis are usually below 50%-60%, and ort/to-substitu-tion to the nitro group is mandatory, this methodology is extraordinarily powerful for constructing indoles with substitution in the benzene ring. 

The Bartoli process has been employed effectively in the synthesis of 7-substituted indoles including 7-alkoxy (15), 7-alkyl (18) , and 7-formal indoles (21). Although the yields are only moderate, this process does provide a simple entry into indoles which were heretofore difficult to obtain. 

Recently, the Bartoli indole synthesis was extended to solid supports. In contrast to the earlier reports in the liquid phase, o,o-unsubstituted nitro analogs (see 25) prove to be useful substrates. In addition, fluoro/chloro substituted nitro derivatives are well tolerated, which typically undergo nucleophilic substitution under Bartoli conditions in the liquid phase. 

The Bartoli indole synthesis [24] is an excellent method for preparing 7-bromoindole (21) [29a, 30]. 

Bartoli, G. Bosco, M. Carlone, A. Locatelli, M. Melchiorre, P. Sambri, L. (2004) Asymmetric catalytic synthesis of enantiopure N-protected 1,2-amino alcohols., Org. Lett., 6 3913-3915. 

Baeyer-Villiger oxidation, 83 Bartoli indole synthesis, 80 bauerine B, 196... 

The synthesis of 7-substituted indoles from ortfe-substituted nitroarenes and alkenylmagnesium halides is known as the Bartoli reaction.315 Usually, ortfe-unsubstituted nitroarenes give complex mixtures of products. In some cases... 

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