Indoles silver® carbonate

The primary product of the Heck type ring closure is an indole derivative containing an exocyclic double bond. This compound, however in most cases isomerises spontaneously to the aromatic isomer. In the example shown in 3.9. the addition of silver carbonate prevented the isomerisation of the double bond into the five membered ring.12... 

As the first application of Heck reaction in making heterocyclic compounds — namely indole derivatives, the Mori-Ban reaction has been widely used in variety synthesis of indoles. In a program to synthesize CC-1065 analogs, Sundberg prepared indole 19 from o-bromo-JV-allylaniline 18 in an excellent yield using the Jeffrey s conditions. Silver carbonate and sodium carbonate were less effective than triethylamine. 

Conceptually it would be possible to prepare N-silylmethyliminium salts by the addition of an electrophile to the p carbon of N-silylmethylenamines [Eq. (5)]. The reaction of l-(trimethylsilylmethyl)indoles with silver fluoride is reported to be initiated by the addition of silver cation to the 3-position to form N-silylmethyliminium fluoride 44, whose desilylation by fluoride ion leads to azomethine ylides 45 (86JA1104). This is the only example known for the reaction depicted by Eq. (5). The narrow application of this method may arise from the lack of a general preparation for N-silylmethylenamines. 

Stringent conditions were required as azoles are susceptible to oxidative homocoupling and electron-rich indoles are prone to decomposition under oxidative conditions. Silver(I) carbonate displayed superior reactivity compared to AgOAc and Ag20. 

Silver(I) carbonate outperformed other oxidants, such as Ag20 (39%) and AgOAc (42%), using thiophene and N,N-(Boc)2-allylamine as the model system. The reaction was highly regioselective (>99 1) to afford the ( )-isomer exclusively. C5-01efination was achieved for 2-substituted and 2, 3-disubtituted thiophenes, whereas C3-vinylation was obtained for 2,5-disubstituted thiophenes. 3-Methylthiophene afforded a 5 2 mixture of 2- and 5-olefinated products. Notably, no al-lylic migration or partial deprotection was detected. Other het-eroarenes, such as indole, A-methylindole, benzothiazole, ben-zoxazole, and thiazole, were incompatible however, additional allylamines could be utilized. 

Silver(I) carbonate functioned as an co-oxidant with TEMPO. Tricyclohexylphosphine was employed to suppress homocoupling between heteroarenes. Substituted thiophenes, furans, and indoles could be selectively olefinated (C5-alkenylation for thiophenes and furans, C3-alkenylation for indoles, E/Z <99 1). Unsubstituted thiophenes produced poor yields (24%) however, formyl, acetyl, and ketyl substituents were well tolerated. For electron-deficient substrates, tricyclohexylphosphine was reduced to 10 mol % to achieve good conversions. A variety of ketones could be employed using 2-methyl thiophene as a coupling partner. 

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