Copper , catalyzed cyclization

In an approach toward the synthesis of tetraponerine, Gevorgyan and co-workers explored the double pyrrolization of pyrimidine derivatives 276 via a copper-catalyzed cyclization to give tricycles 277 (Equation 76) <2002OL4697, 2004JOC5638>. 

In contrast to the palladium-catalyzed reactions, little attention has been paid to other transition-metal catalysts. Recently some efficient reactions using copper(i or 11), gold(m), platinum(n), and tungsten(O) have been developed for the synthesis of nitrogen-heterocycles. The copper-catalyzed cyclizations of 2-alkynylaniline derivatives into... 

Scheme 41 Benzothiazole synthesis via copper-catalyzed cyclization-elimination...

Benzoxazoles are found in a variety of natural products and routinely find use in pharmaceutical research. They are generally made by condensation of a 2-aminophenol with a carboxylic acid or oxidative cylization of an imine intermediate. A mild copper-catalyzed cyclization of o/t/ o-haloanilides to give benzoxazoles 209 has been reported (Scheme 62) <2006JOC1802>. This route is conceptually different to the aforementioned methods in that the starting material is a 2-haloaniline rather than a 2-aminophenol. The reaction conditions tolerate various functional groups in the amide portion of the molecule. 

The synthetic utility of copper-catalyzed cyclizations has been well demonstrated in the synthesis of alkaloids. For example, the enaminone 241, prepared for the (/ )-keto ester 240 through multiple steps, gave the carba-zolone 242, Scheme 64, which was elaborated further to Aspidosperma alkaloid analogues (90TL879, 90TL883). 

Scheme 45. Copper-catalyzed cyclization of a Fischer carbene to a spirocyclopentadiene.

Application of carbon-carbon cross-coupling/67C-electrocyclization cascade reactions in pyridine synthesis is well known. Larock and coworkers developed a palladium-catalyzed coupling of vinylic imines 279 with terminal alkynes 280 followed by subsequent copper-catalyzed cyclization of 281 to give aryl, vinyl, and alkyl-substituted pyridines 282 in moderate yields. ... 

P-carbohnes [29] (Schane 3, equation 1). A variety of secondary amines were employed, and the method was adapted to the preparation of pyrrolo[3,2-/lindoles and dipyrrolo[3,2-h 2, 3 -c]pyridines [30]. Cacchi and colleagues synthesized 3-aroylindoles from the copper-catalyzed cyclization of lV-(2-iodoaryl)enaminones (equation 2) [31]. The latter were prepared from 2-haloanilines and a,p-ynones, which can react directly with 2-iodoaniline under the copper protocol to give 3-benzoyl-2-phenylindole (76%), thus bypassing the enaminone. Patel described a copper-catalyzed 3-aroylindole synthesis from 2-alkynylated... 

Batey s group reported a general method for the formation of benzoxazoles via a copper-catalyzed cyclization of ort/zo-haloanilides in 2006 (Scheme 2.135). This approach complements the more commonly... 

SCHEME 3.59 Synthesis of imidazo[l,2-a]pyridines through copper-catalyzed cyclization/ oxidation process [65]. 

The preparation of imidazo[l,2-a]pyridines has been achieved using a copper-catalyzed cyclization/oxidation process (Scheme 3.59 and Example 3.8) [65]. Using a conunon copper salt and bipyridine as the stabiUzing/solubiUzing ligand, outstanding yields of the... 

As with the synthesis of benzofurans, the use of catalytic intramolecular C—O bond forming reactions has proved to be a popular route to benzoxazoles. Evindar, Batey and co-workers reported a copper-catalyzed cyclization of o-bromobenzanilides to generate a variety of 2-substituted benzoxazoles (Scheme 24.34) [123]. A number of similar cyclizations have also been reported [63,124,125]. 

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