One-Pot Tandem Hiyama Alkynylation/Cyclizations by Palladium(II) Acyclic Diaminocarbene (ADC) Complexes Yielding Biologically Relevant Benzofuran Scaffolds

Abstract

A series of palladium acyclic diaminocarbene (ADC) complexes of the type cis -[(R 1 NH)(R 2 )methylidene]PdCl 2 (CNR 1 ) [R 1 = 2,4,6-(CH 3 ) 3 C 6 H 2 : R 2 = NC 5 H 10 ( 2 ); NC 4 H 8 ( 3 ); NC 4 H 8 O ( 4 )] were used not only to perform the C sp 2 –C sp Hiyama coupling between aryl iodide and triethoxysilylalkynes but also to subsequently carry out the one-pot tandem Hiyama alkynylation/cyclization reaction between 2-iodophenol and triethoxysilylalkynes, giving a convenient time-efficient access to the biologically relevant benzofuran compounds. The palladium ADC complexes ( 2 – 4 ) were conveniently synthesized by the nucleophilic addition of secondary amines, namely, piperidine, pyrrolidine, and morpholine on the cis -{(2,4,6-(CH 3 ) 3 C 6 H 2 )NC} 2 PdCl 2 in moderate yields (ca. 61–66%).

Palladium Acyclic Diaminocarbene (ADC) Triflate Complexes as Effective Precatalysts for the Hiyama Alkynylation/Cyclization Reaction Yielding Benzofuran Compounds: Probing the Influence of the Triflate Co‐Ligand in the One‐Pot Tandem Reaction

“…With the intent of examining the influences of the acyclic diaminocarbene ligand [(R 1 NH)(R 2 )methylidene] [R 1 = 2,4,6‐(CH 3 ) 3 C 6 H 2 : R 2 = NC 4 H 8 ; NC 5 H 10 ] alongside an anionic triflate (OCOCF 3 ) co‐ligand, we undertook the synthesis of the palladium acyclic diaminocarbene type complexes cis ‐[(R 1 NH)(R 2 )methylidene]Pd(OCOCF 3 ) 2 (CNR 1 ) [R 1 = 2,4,6‐(CH 3 ) 3 C 6 H 2 : R 2 = NC 4 H 8 ( 1 ); NC 5 H 10 ( 2 )] for their utility in one‐pot tandem Hiyama alkynylation/cyclization reaction. The initiative becomes relevant particularly from the perspective of chloro analogues of the formula, cis ‐[(R 1 NH)(R 2 )methylidene]PdCl 2 (CNR 1 ) [R 1 = 2,4,6‐(CH 3 ) 3 C 6 H 2 : R 2 = NC 5 H 10 ; NC 4 H 8 ; NC 4 H 8 O], that were effective precatalysts for the one‐pot tandem Hiyama alkynylation/cyclization reaction. Particularly, the palladium acyclic diaminocarbene complexes 1 and 2 were synthesized from the chloro derivatives cis ‐[(R 1 NH)(R 2 )methylidene]PdCl 2 (CNR 1 ) [R 1 = 2,4,6‐(CH 3 ) 3 C 6 H 2 : R 2 = NC 5 H 10 ; NC 4 H 8 ] by treatment with AgOCOCF 3 under ambient conditions in excellent yields ( ca .…”

“…With our interest lying in exploring the potential of transition metal N‐heterocyclic carbene complexes in homogeneous catalysis and in biomedical applications, we have explored the utility of various type of singlet carbene ligand scaffolds namely, the imidazole, benzimidazole, 1,2,4‐triazole based ones,, abnormal carbenes, bicyclic and the tricyclic carbene systems . In this connection, we became interested in another new motif, particularly that of the acyclic diaminocarbene ligands, for their utility in time efficient tandem reactions ,. Specifically, we sought to investigate the potential of the triflate derivatives of the palladium acyclic diaminocarbene complexes in the one‐pot tandem Hiyama alkynylation/cyclization reaction yielding biologically relevant benzofuran compounds.…”

“…Specifically, we sought to investigate the potential of the triflate derivatives of the palladium acyclic diaminocarbene complexes in the one‐pot tandem Hiyama alkynylation/cyclization reaction yielding biologically relevant benzofuran compounds. It is worth noting that as benzofuran motifs are ubiquitous in many bioactive compounds, a convenient time efficient approach like that of one‐pot tandem Heck alkynylation/cyclization reaction and one‐pot tandem Hiyama alkynylation/cyclization reaction, towards its synthesis are of significant interest.…”

1,4‐Conjugate Addition of Aryl boronic Acids on Cyclohexenone as Catalyzed by Rhodium(I) Complexes of C2‐Symmetric Bioxazoline Fused N‐heterocyclic Carbenes

“…With our longstanding interest in exploring the utility of the transition metal complexes of the N‐heterocyclic carbene ligands in catalytic and biomedical applications, we became interested in exploring the catalytic potential of rhodium N‐heterocyclic carbene complexes, and have recently reported their application in asymmetric transfer hydrogenation reactions, and proceeding further along the line, we set out to explore their utility in the 1,4‐conjugate addition using aryl boronic acid and α , β ‐unsaturated carbonyl compounds. We have also reported the use of transition metal based N‐heterocyclic carbene complexes for C‐C bond forming reactions like the bifunctional catalysis of the base‐free Micheal addition reactions, C‐C cross coupling C‐N bond formation in β ‐enaminones, hydroamination of alkynes and alkenes, C‐B bond forming reactions, tandem reactions involving Heck alkynylation/cyclization reaction and in the Hiyama alkynylation/cyclization reactions, hydrosilylation, cyanosilylation and a transfer hydrogenation reactions …”

Functionalized Benzofurans via Microwave‐Promoted Tandem Claisen‐Rearrangement/5‐endo‐dig Cyclization

“…Traditionally, these reactions are mediated by bases such as Cs 2 CO 3 in polar, aprotic solvents at elevated temperatures , but only for very few examples microwave irradiation was used to accelerate the reaction . In recent years, metal catalysis has been intensively investigated for this intramolecular heteroannulation, including, inter alia, rhodium , palladium , and indium catalysts . Transition metal catalysis offers the opportunity to combine the heteroannulation with additional steps to tandem sequences, which ultimately results in the formation of 2,3‐disubstituted benzofurans.…”