Pyrroles from diynes

One-pot Multi-Component Synthesis of Azaindoles and Pyrroles from One Molecule of silicon-Tethered Diyne and Three or Two Molecules of Organo-nitriles Mediated by Zirconocence. 

Zhang S, Sun X, Zhang WX et al (2009) One-pot multicomponent synthesis of azaindoles and pyrroles from one molecule of a silicon-tethered diyne and three or two molecules of organonitriles mediated by zirconocene. Chem Eur J 15 12608-12617... 

Gold complexes can also be utilized as catalysts for the synthesis of pyrroles from 1,5-diynes. 2,5-Dimethylpyrrole is synthesized from the reaction of hexa-l,5-diyne and ammonia in the presence of a gold-carbene complex, Au-I [13] ... 

Poly(unsaturated) substrates can be used for sequential hydroamination/5-entio-cyclization reactions, which can be formally - but not mechanistically - seen as sequential inter/intramolecular hydroamination, to yield heterocyclic products, e.g., pyrroles from 1,4-diynes (30) [201]. 

The condensed isobenzofuran derivative l,3-dimethyl-2,5,7-triphenyl-2/f-furo[3,4-/]isoindoloquinone (64), has been prepared in four steps from a pyrrole derivative143 (Scheme 79) a thiophene analog of64 has been obtained in a similar manner.144 Key intermediates in both types of reactions are condensed rhodacyclopentadienes (cf. 63) which are obtained from appropriate diynes. 

Titanium-catalyzed hydroamination of the diyne 470 has been demonstrated to proceed via a 5-r r/o- /g-cyclization affording the pyrrole 471 (Equation 130). Pyrroles have also been isolated as products from similar reactions involving related 1,5-diynes, which resulted from S-exo-dig-annuhitiom <2004OL2957>. 

Construction of the phosphole ring, with one useful exception, is accomplished by methods that are quite different from those employed for the N, S, O ring systems. Because of fundamental differences in the chemistry of phosphines versus amines, none of the familiar carbonyl condensation processes are known to be applicable to phosphole synthesis. Thus an attempt to use the Paal-Knorr condensation of 1,4-dicarbonyl compounds with PhPH2 <65JCS2184> and with PH3 <88ZOB783> failed to give phospholes. The only successful method known to the present that is common to both the phosphole and pyrrole ring systems is the condensation of 1,3-diynes with primary phosphines... 

A domino Mannich/aza-Michael reaction was applied to the synthesis of 2,5-cis-configured polysubstituted pyrrolidines from y-malonate-substituted a,P-unsaturated esters with N-protected arylaldimines [117]. In this report, bifunctional thioureas were trialed with the Takemoto catalyst, being the most efficient with respect to yield as well as enantiomeric and diastereomeric excess. In a separate approach, the Garcia-Tellado group approached the pyrrole ring system 234, beginning with a tertiary skipped diyne 233 and a primary amine (Scheme 7.50). 

Schulte [285, 286] and later Chalk [287] described the Cu(I)-catalyzed synthesis of symmetrical 2,5-diarylpyrroles 261 from conjugated diynes 257 and primary amines 258. The reaction is believed to proceed via the transition metal-catalyzed hydroamination [33, 288-291] leading to tautomeric aminoenyne 259 or homopro-pargylic imine 260 intermediates, which further undergo 5-endo-dig cyclization to furnish pyrrole product 261 (Scheme 8.95). 

The preparation of fnnctionalized pyrroles has been accomplished through titanium-mediated reactions (Scheme 3.74) [79]. The first step in the process involves the generation of a metaUocycle from the reaction of a diyne with the titanium reagent that was generated in solntion. Once formed, treatment of the titanacycle with an activated imine followed by hydrolysis generated the pyrrole. The overall reaction can be described as an imino aza-Nazarov cyclization, and the process generated good to excellent yields of the 3-aminopyrroles. 

A catalyst prepared in situ from TiCLj and f-BuNH2 also catalyzes the reaction of a 1,3-diyne and primary aromatic amines, giving rise to pyrroles in low yields [14] ... 

Using a similar dual gold catalysis of diynes model, Hashmi, Hansmann, and coworkers explored a dual gold-catalyzed cyclization of 3,4-diethynylthiophenes to generate pentaleno[c]thiophenes through gold-vinylidenes and C-H bond activation. In these cases, 5-e (io-dig cyclization pathway was observed. This protocol can be used to construct thiophene/furan or thiophene/pyrrole 101 system skeleton from 3,4-diethynylthiophene derivatives 100 (Scheme 12.46) [49]. 

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