Alkenylation of indoles

A similar strategy enabled the 2-alkenylation of indoles using catalytic palladium chemistry (Equation (139)).121... 

A C-H activating Pd-catalyzed alkenylation of indole is regiospecific for 2-substitution when the nitrogen carries a 2-pyridylmethyl substituent (Equation 169) <2005CC1854>. Under the same conditions A -Bn-indole reacted with methyl acrylate regioselectively to afford 3-isomers in 95% yield. 

Abstract This review details recent developments in the Pd-catalyzed C-H bond arylation and alkenylation of indoles and pyrroles, aromatic heterocycles that are frequently displayed in natural products and medicinal agents. 

Pd-Catalyzed C-H Alkenylation of Indole and Pyrrole 4.1 Mechanisms of Pd-Catalyzed C-H Bond Alkenylation... 

Scheme 42 Proposed mechanism for intramolecular alkenylation of indoles...

Capita, E., Brown, J.M. and Ricci, A. (2005) Directed palladation fine tuning permits the catalytic 2-alkenylation of indoles. Chem. Commun., 1854-6. 

Grimster, N.P., Gauntlett, C., Godfrey, C.R.A. and Gaunt, M.J. (2005) Palladium-catalyzed inter-molecular alkenylation of indoles by solvent-controlled regioselective C—H functionalization. 

Meanwhile, the alkenylation of indoles preferentially occurs at their C3 position. Gaunt and coworkers [47] reported that treatment of unsubstituted indole with... 

SCHEME 10.35 Gaunt s regioselective intermolecular alkenylation of indole. 

Grimster NP, Gauntlett C, Godfrey CRA, Gaunt MJ (2005) Palladium-catalyzed intermolecu-lar alkenylation of indoles by solvent-controlled regioselective C-H functionalization. Angew Chem Int Ed 44 3125-3129... 

C-H alkenylation and decarboxylation (Scheme 4.48) [53], as in the reaction of benzoic acids described above (Schemes 4.28 and 4.29). Since the palladium-catalyzed Fujiwara-Moritani type direct alkenylation of indoles usually takes place at the C3-position, it enables alkenylation at a position complementary to that of the Fujiwara-Moritani reaction, being of unique synthetic utility. On the other hand, the reaction of thiophene-2-carboxylic acid leads to the formation of a mixture of C2- and C3-alkenylated products. Decarboxylation may take place too early to complete directed C-H alkenylation at the C3-position. In contrast, the exclusive C3-alkenylation on a thiophene ring is possible under rhodium catalysis (Scheme 4.49) [34b]. 

Scheme 16.2 Syntheses of clavidpitic add and chanodavine-l enabled by C-H alkenylation of indoles at the C3 position.

Intermolecular direct C(3)-alkenylation of indoles using palladium(II) as catalyst and oxygen as the oxidant has been achieved. The reaction shows complete regio- and stereo-selectivity all products are ii-isomers at the C(3)-position, and no Z-isomers or 2-substituted products are detected. Aerobic a, -dehydrogenation of aldehydes and ketones is catalysed by Pd(TFA)2/4,5-diazafluorenone. The cleavage of a-C-H bond of the ketone has been identified as the turnover-limiting step of the catalytic mechanism. ... 

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