Intramolecular reactions Larock indole synthesis

The most popular Pd-catalyzed method for the production of furans and benzofurans involves reactions of alkynols. Acyclic alkynols are converted into furans, while benzene substituted alkynols are transformed into benzofurans. The use of this strategy is widespread for the synthesis of benzofurans however, it is occasionally used for the syntheses of furans. For example, intramolecular alkoxylation of alkyne 189 proceeds via an alkenylpalladium complex and subsequent carbonylation to form furan 190 [156, 157]. In addition, 3 -hydroxyalkyl-benzo[/)J furans were prepared by Bishop et al. via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis [158]. In a related series of experiments, Qing demonstrated that alkynes 191 could be efficiently converted into furans 192 [159]. 

Larock heteroannulation reaction was further extended and an intramolecular Larock indole synthesis of 2-chloroanilines bearing tethered acetylenes 106 was developed for the elaboration of a variety of polycyclic indole skeletons 107, for example, in 108-112. This intramolecular indolization method unveiled an unusual >sy -anidopalladation pathway of a tethered alkyne. The major side product is the dechlorinated starting material as a result of a reductive process. 

Boger and coworkers reported the first total synthesis of chloropeptin II and later its transformation into chloropeptin I (2009JA16036). The key step to this total synthesis was macrocycHzation of peptide 31 by an intramolecular Larock indole heteroannulation. This intramolecular reaction between a substituted 2-bromoaniline with a removable terminal alkyne substituent afforded simultaneous regioselective indole ring formation and macrocycli-zation. The TES substituent of the alkyne dictates indole cyclization regio-selectivity (Scheme 20). 

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