Vinylations indoles, palladium acetate

A mixture of the appropriate phenyl vinyl sulfone, tri-o-tolylphosphine, palladium (II) acetate, triethlamine and (R)-5-bromo-3-(N-methylpyrrolidinylmethyl)-lH-indole in anhydrous acetonitrle was heated at reflux under nitrogen. The resultant reaction mixture was evaporated under reduced pressure, and the residue was column chromatographed using silica gel and elution with methylene chloride/absolute ethanol/ammonia to afford the (R )-5-trans-(2-phenylsulfonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-lH-indole. 

Metal-catalysed cyclization is an increasingly important method of synthesis (reviews [B-4I, 2998, 3069, 3501, 3505 ). Bis(acetonitrile)dichloropalladium promotes cyclization of an alkynyl carbamate with epoxypropane and a vinyl chloride [3438] an alkynylaniline is converted into an indole by heating with a palladium chloride-triphenylphosphine catalyst [3631]. Mercury(II) acetate is an effective promotor of the cyclization of the alkenylaniline (37.2) to a reduced carbazole [3861]. 

There are also several indole syntheses which are based on the use of arylhydroxyamines and which involve a [3,3]-sigmatropic rearrangement similar to that involved in Fischer cyclization. Substituted JV-acetylarylhydroxyamines can be vinylated by palladium-catalyzed addition-elimination with vinyl acetate. Under mild heating, rearrangement and cyclization occurs (Scheme 61) <84HCA1647, 88HCA344>. 

The first asymmetric total synthesis of the dimeric indole alkaloid (T)-dispegatrine (51) was accomplished by Cook (Scheme 1). Initially, (T)-lochnerine (52), the monomeric part of 51, was synthesized from 5-methoxy-D-tryptophan ethyl ester (53) via a nine-step operation that included the enolate-mediated palladium-catalyzed cyclization of vinyl iodide 54 as the key reaction. Thus-obtained 52 was treated with thaUium(lll) acetate (0.65 equiv) and BF3 Bt20 (3.0 equiv) at —40 °C to — 10°C to... 

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