Pyrroles copper catalyzed synthesis

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>. 

A copper-catalyzed homocoupling of ketoxime carboxylates 19 was invented to afford symmetrical pyrroles 20. Treatment of ketoxime with CuBr in the presence of NaHSOs as an additive in dimethyl sulfoxide (DMSO) at elevated temperatures led to the synthesis of pyrroles 20 in good yield (14GC112). 

An interesting enantioselective copper-catalyzed coupling of pyrroles 261 with isatins 260 was reported for the synthesis of 3-substituted-3-hydroxy-2-oxindoles 262. This reaction proceeds in moderate to high yield with high ee (140L3192). 

An interesting pyrrole synthesis is based on an application of a copper catalyzed 1,4-addition of an activated CH2 group to a conjugated ene— dizo system [89]. 

The copper-catalyzed reaction has been employed in the synthesis of various pyrrole derivatives (Figure 20.1) [10],... 

Double N-arylation can also be conducted by using copper catalysts. In 2007, Martin, Li, and co-workers independently reported pyrrole synthesis via copper-catalyzed C—N bond formation between l,4-dihalo-l,3-dienes and amines [13]. They applied this methodology to carbazole synthesis (Scheme 23.9). In general, diiodobiaryl gave better results than dibromobiaryls. As a nitrogen source, carbamates and amides were investigated in their reports. 

An efficient Cu-catalyzed cycloisomerization of alkynyl imines into the 2-monosubstituted and 2,5-disubstituted pyrroles was reported by Gevorgyan and coworkers (Scheme 8.3). This methodology was efficient to the synthesis of various types of fused heteroaromatic compounds and even synthesis of ( ) monomorine. A C(sp )-H of the substrate was activated during this copper-catalyzed pyrrole formation [12]. Moreover, they also realized the... 

Chiba and coworkers developed a Cu(NTf2)2-catalyzed synthesis of pyrroles from a-ethoxycarbonyl vinyl azides and ethyl acetoacetate through the 1,4-addition reaction of the acetoacetate to the vinyl azides [19]. Jiao and coworkers reported a copper- or nickel-catalyzed highly selective denitrogenative annula-tion of vinyl azides with acetaldehydes to 2,4- and 3,4-diaryl-substituted pyrroles. Cu(OAc)2 could catalyze the formation of 2,4-diaryl-substituted pyrroles. This selective polysubstituted pyrrole synthesis could proceed under mild conditions without any acidic or basic conditions [20] (Scheme 8.8). 

CuOTf-catalyzed synthesis of polysubstituted pyrroles from a-diazoketones, nitroalkenes, and amines was reported by Lu, Wang, and coworkers. The corresponding polysubstituted pyrroles could be obtained in moderate yields using air as the oxidant. This cascade process of the polysubstituted pyrrole formation involves an NH insertion of carbene, a copper-catalyzed oxidative dehydrogenation of amine, and a [3+2] cycloaddition of azomethine ylide [21] (Scheme 8.9). 

Isocyanides have been explored extensively in cascade reactions, due to their unusual reactivities to form multiple bonds in a one-pot manner with remarkable versatility in producing heterocycles. The reaction of isocyanides with Cu(I) in the presence of base could form the a-cuprioisocynanides, which could undergo formal [3+2] cycloaddition with alkynes to form pyrrole rings. Recently it was reported that the a-cuprioisocynanide intermediates occurred in the copper-catalyzed cascade reaction of isocyanides with A/-(2-haloaryl)propiolamides 109 for the synthesis of... 

In a subsequent report, they described an alternative synthesis of pyrroles through a two sequential copper-catalyzed vinylations of hydrazydes/cyclization strategy (Scheme 41) [130]. Alternatively, the synthesis of various A -acylpyrroles was accomplished by Li through a copper-catalyzed double A -alkenylation of amides [131]. For more details see the chapter devoted to the synthesis of heterocycles by means of arylation/vinylations. 

The addition of 1,3-dicarbonyl compounds to /3-chloroazoalkenes is the basis of a pyrrole synthesis (Scheme 70a) 81TL1059). Pyrroles are also obtained by the reaction of enamines with azoalkenes (Scheme 70b) (79TL2969,81TL1475), and the copper(II) chloride catalyzed addition of 1,3-dicarbonyl compounds to arylazoalkenes (Scheme 70c) (82JOC684). 

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