Rhodium carbene reactions 3- indoles

Rhodium-Catalyzed Reactions via Zwitterionic Intermediates Diazo compounds are also known to undergo insertion into C—H bonds by action of a rhodium-based catalyst, giving rise to a zwitterionic species characterized by a similar reactivity to that of onium ylide species [170]. Recently, Hu et al. [171] have described that zwitterionic intermediates 150, obtained by carbene insertion into a C—H bond in indoles, can be trapped by imine 151 activated by a chiral Brpnsted acid. After optimization of conditions, three-component reactions carried out at -10 °C in toluene afforded the desired products 152 in high yields, >20 1 diastereoselectivities for the flnft-isomer, and 84-99% ee (Scheme 3.66). 

Tryptophan offers an indole side chain that can be used for ligation chemistry. A water-compatible rhodium carbene can be added to the indole ring (19) [105,139]. The reactive species is generated in situ by a conjugated diazo compound by a rhodium catalyst like rhodium(II) acetate [63,139,149]. The reaction takes place in the two- and three-position of indole. Thus, a mixture of N-alkylated and C-alkylated product is obtained. It is necessary to add hydroxylamine hydrochloride as an additive to bind to the distal rhodium carbenoid complex. The usage of this salt lowers the pH value below 3.5 and therefore limits the scope of this methodology. As a side reaction, the carbene inserts into the O-H bond of water (Table 6). 

The Rh-catalyzed annulation of triazoles has been explored by several investigators as a novel indole synthesis. Fokin s team generated azavinyl carbenes with rhodium and parlayed this reaction into an indole synthesis (equation 3) [54], Davies and colleagues described a one-pot indole synthesis from tosyl azide and cyclohexenyl derivatives involving an in situ triazole formation (equation 4) [55], and Lin reported a synthesis of 3-indolylimines using a similar approach (equation 5) [56]. Miura and coworkers effected the Rh-cat-alyzed intramolecular synthesis of 3,4-fused indoles... 

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