Pyrrole syntheses based on titanium-catalyzed hydroamination of diynes

Titanium-catalyzed hydroamination of 1,4- and 1,5-diynes by primary amines leads to imino-alkynes that undergo in situ 5-endo dig and 5-exo dig cyclization reactions, respectively. The products are 1,2,5-trisubsituted pyrroles accessed directly from readily available diyne starting materials.     

Pd-catalyzed decarboxylative coupling of propiolic acids: one-pot synthesis of 1,4-disubstituted 1,3-diynes via Sonogashira-homocoupling sequence

One-pot synthesis of symmetric 1,4-disubstituted 1,3-diynes from iodoarenes and propiolic acid via Sonogashira reaction followed by Pd-catalyzed decarboxylative homocoupling is developed in high yields. Also, this system allows the one-pot synthesis of unsymmetric 1,4-disubstituted 1,3-diynes by cross-coupling of two different 3-substituted propiolic acids.     

Unprecedented Cu-catalyzed coupling of internal 1,3-diynes with azides: one-pot tandem cyclizations involving 1,3-dipolar cycloaddition and carbocyclization furnishing naphthotriazoles

A one-pot protocol for the synthesis of triazole-annulated polyheterocycles via metal-catalyzed coupling of internal 1,4-disubstituted 1,3-diynes and organic azides has been described. The mechanistic rationale for the reaction suggests tandem cyclizations involving copper-catalyzed cycloaddition and 6-endo carbocyclization reactions. The cascade cyclization leads to an increase in molecular complexity to furnish naphtho[1,2-d]triazoles in satisfactory yields. The generality of the method has been demonstrated by using a series of aromatic/aliphatic azides and symmetrical internal 1,3-diynes.     

Efficient domino approaches to multifunctionalized fused pyrroles and dibenzo[b,e][1,4]diazepin-1-ones

Efficient domino approaches for the synthesis of multifunctionalized tricyclic fused pyrroles and dibenzo[b,e][1,4]diazepin-1-ones have been established. The reaction pathways were controlled by varying enaminones with different substituted patterns to give a series of new fused pyrroles and dibenzo[b,e][1,4]diazepin-1-ones selectively. The complete anti diastereoselectivity was achieved for the first reaction.     

Rhodium-catalyzed enantioselective synthesis, crystal structures, and photophysical properties of helically chiral 1,1'-bitriphenylenes

The highly enantioselective synthesis of helically chiral 1,1'-bitriphenylenes has been achieved via rhodium-catalyzed double [2 + 2 + 2] cycloaddition of biaryl-linked tetraynes with 1,4-diynes (up to 93% ee). Crystal structures and photophysical properties of these helically chiral 1,1'-bitriphenylenes have also been studied.     

Synthesis of polysubstituted N-H pyrroles from vinyl azides and 1,3-dicarbonyl compounds

Two synthetic methods for tetra- and trisubstituted N-H pyrroles are presented: (i) the thermal pyrrole formation by the reaction of vinyl azides with 1,3-dicarbonyl compounds via the 1,2-addition of 1,3-dicarbonyl compounds to 2H-azirine intermediates generated in situ from vinyl azides; (ii) the Cu(II)-catalyzed synthesis of pyrroles from alpha-ethoxycarbonyl vinyl azides and ethyl acetoacetate through the 1,4-addition reaction of the acetoacetate to the vinyl azides. By applying these two methods, regioisomeric pyrroles can be prepared selectively starting from the same vinyl azides.     

Cu-catalyzed tandem C-N bond formation for the synthesis of pyrroles and heteroarylpyrroles

A highly efficient Cu-catalyzed tandem C-N bond-forming reaction of 1,4-dihalo-1,3-dienes has been developed. The transformation allows the synthesis of pyrroles and heteroarylpyrroles with a wide variety of functional groups and substitution patterns from readily available precursors.     

1,4‐Dihydropyrrolo[3,2‐b]pyrrole and Its π‐Expanded Analogues

Various approaches to the synthesis of 1,4‐dihydropyrrolo[3,2‐b]pyrroles are summarized. Many two‐ and three‐step reaction sequences have been developed, and have allowed access to a broad variety of structures, including not only the parent 1,4‐dihydropyrrolo[3,2‐b]pyrroles, but also their π‐expanded analogues. The newest approaches are critically compared with older strategies. The reactivity of these compounds is also reviewed, with special emphasis on electrophilic aromatic substitution. The synthesis of indolo[3,2‐b]indole derivatives has been the subject of intense investigation. Overall, a few interesting and ingenious approaches toward these ladder‐type heteroacenes have been proposed, reaching total yields in the region of 30 %. Finally, the optical, electrochemical, and other physicochemical properties are presented in the broader perspective of heteropentalenes. The parent 1,4‐dihydro‐pyrrolo[3,2‐b]pyrroles constitute the most electron‐rich, simple, aromatic heterocycles, and their simple derivatives and π‐expanded analogues possess strong violet, blue, or green fluorescence both in solution and in the solid state.     

Ruthenium-catalyzed hydrophosphinylative cyclization of 1,6-diynes. Stereoselective synthesis of exocyclic 1,3-dienylphosphine oxides

The first catalytic synthesis of exocyclic 1,3-dienylphosphine oxides was achieved by the ruthenium-catalyzed selective hydrophosphinylative cyclization of 1,6-diynes. A plausible mechanism involving a ruthenacyclopentatriene intermediate is proposed on the basis of the DFT calculations of model ruthenium complexes.     

Nucleophilic displacement of aromatic fluorine. Part V. Use of nitrogen heterocycles as nucleophiles

The scope of the nucleophilic displacement of aromatic halogens on 1,4-benzodiazepine precursors by the anions of pyrroles, pyrazoles and imidazoles was studied both with and without electron-withdrawing substitutents on the heterocyclic nucleophiles. Some of the products proved to be useful intermediates for the synthesis of novel fused 1,4-benzodiazepines.     

1,1,2-Trihaloalkenes and Dimeric Acetylenes from Acetylenic Tellurium Species

Reaction of 1-teliuroalk-1-ynes with bromine and iodine or with Cu(II) chloride furnishes respectively 1,1,2-trihaloalkcnes and 1,4-disubstituted 1,3-diynes.     

N-propargylic beta-enaminones: common intermediates for the synthesis of polysubstituted pyrroles and pyridines.

N-Propargylic beta-enaminones have been used as common intermediates for the synthesis of polysubstituted pyrroles and pyridines. Best results have been obtained using DMSO as solvent. In the presence of Cs(2)CO(3) N-propargylic beta-enaminones are cyclized to pyrroles in good to high yields, whereas omitting bases and using CuBr leads to the selective formation of pyridines.     

Diastereoselective Synthesis of Cyclododeca-1,6-diallenes ( = cyclododeca-l,2,6,7-tetraenes)

The synthesis of substituted cyclododeca-1,6-diallenes.( = cyclododeca-1,2,6,7-tetraenes) from cyclododeca-5,11-diyne-1,4-diols is described (Schemes 1 and 3). The ca. 1:1 mixtures of the stereoisomers of the cyclododeca-1,6-diallenes were formed in high yields from the ca. 1:1 diastereoisomer mixtures of the 1,4-disubstituted cyclododeca-5,11-diynes by reactions with Me₂CuLi or t-BuMgCl/Cu^II. In mechanistically relevant experiments with the pure diastereoisomers of 1,4-dimethylcyclododeca-5,11-diyne-1,4-diol, it is demonstrated that the configuration is conserved in these reactions. The first synthesis of a 1-substituted cyclododeca-2,8-diyne bearing only one propargylic leaving group gives access to a mixed 12-membered allen-yne (Scheme 5).     

Solvent‐Controlled C2/C5‐Regiodivergent Alkenylation of Pyrroles

A solvent‐controlled C2/C5‐selective alkenylation of 3,4‐disubstituted pyrroles has been developed. The C3 substituent of pyrroles proved crucial to the regioselectivity. Substrates bearing directing groups at the C3 position exhibited excellent C2‐selectivities in chelation‐assisted C?H activation in toluene or 1,4‐dioxane. However, a DMSO/DMF solvent system could override the chelation effect of weak directing groups, such as carboxylate and carbonyl groups, favoring instead regioselectivity towards the more electron‐rich C5 position. A series of 3‐carboxylate and 3‐carbonyl pyrroles were tested and showed moderate to good yields with good regioselectivities for both C2‐ and C5‐alkenylation process.     

Ruthenium-catalysed conversion of 1,4-alkynediols into pyrroles

Various 1,2,5-substituted pyrroles have been synthesised from 1,4-alkynediols using a ruthenium catalysed isomerisation to give the corresponding 1,4-dicarbonyl compounds, which undergo in situ cyclisation to pyrroles in the presence of amine.     

Ruthenium-catalysed double trans-hydrosilylation of 1,4-diarylbuta-1,3-diynes leading to 2,5-diarylsiloles

Dihydrosilanes undergo double trans-hydrosilylation with 1,4-diarylbuta-1,3-diynes in the presence of a cationic ruthenium catalyst to afford 2,5-diarylsiloles: in particular, 9-silafluorene is a good hydrosilylating agent to produce spiro-type siloles in good yield.     

CuI/iodine-mediated homocoupling reaction of terminal alkynes to 1,3-diynes

A facile and efficient pathway for CuI/iodine-mediated homocoupling reaction of terminal alkynes to symmetrical 1,4-disubstituted 1,3-diynes in good to excellent yields was reported.     

Heterocyclic alpha-alkylidene cyclopentenones obtained via a Pauson-Khand reaction of amino acid derived allenynes. A scope and limitation study directed toward the preparation of a tricyclic pyrrole library

The synthesis of a novel class of tricyclic pyrroles has been accomplished by using a Pauson-Khand/Stetter/Paal-Knorr reaction sequence. Full details of the Pauson-Khand reaction of amino acid tethered allenynes 4a-e and 9a-d are disclosed. The study of this reaction led to the discovery of an unprecedented substituent effect on the diastereoselectivity of the Mo(CO)6 mediated allenic Pauson-Khand reaction. It was found that amino acid tethered allenynes with aromatic side chains afford alpha-alkylidene cyclopentenones with the opposite diastereoselectivity compared to those with aliphatic side chains. This effect has been attributed to complexation of the metal mediator to the aromatic ring in the substrate. Furthermore, an isomerization of one of the diastereomers of the alpha-alkylidene cyclopentenones was encountered, leading to eventual decomposition. The stable diastereomers were found to react well in the Stetter reaction leading to 1,4-diketones that were converted to pyrroles. The observation that the first generation of 2-alkyl-substituted pyrroles was unstable led to a second generation of 2-carboxamide pyrroles with sufficient stability for biological tests which are in progress.     

New approach to the synthesis of tetrazole-containing buta-1,3-diynes: The total synthesis of 1,4-bis(2-(tert-butyl)-2H-tetrazol-5-yl)buta-1,3-diyne

An approach for the total synthesis of 1,4-bis(2-(tert-butyl)-2H-tetrazol-5-yl)buta-1,3-diyne was reported. Developed approach to the synthesis of 1,4-bis(2-(tert-butyl)-2H-tetrazol-5-yl)buta-1,3-diyne can be used for obtaining different 2,5-bis(tetrazol-5-yl)-disubstituted five-membered heterocycles (e.g. thiophenes, pyrroles, furans etc.), as well as tetrazole-containing monomers for the synthesis of new types of electroconductive and high energetic polymers.     

Trimethylsilyl‐Protected Alkynes as Selective Cross‐Coupling Partners in Titanium‐Catalyzed [2+2+1] Pyrrole Synthesis

Trimethylsilyl (TMS)‐protected alkynes served as selective alkyne cross‐coupling partners in titanium‐catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS‐protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2‐TMS‐pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2‐silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R.