Total Synthesis and Biological Evaluation of (+)‐Neopeltolide and Its Analogues

The stereocontrolled total synthesis of the originally proposed ( 1 ) and correct ( 2 ) structures of (+)‐neopeltolide, a novel marine macrolide natural product with highly potent antiproliferative activity against several cancer cell lines as well as potent antifungal activity, has been achieved by exploiting a newly developed Suzuki–Miyaura coupling/ring‐closing metathesis strategy. Alkylborate 44 , which was generated in situ from iodide 34 , was coupled with enol phosphate 8 by a Suzuki–Miyaura coupling. Ring‐closing metathesis of the derived diene 45 followed by stereoselective hydrogenation afforded tetrahydropyran 47 as a single stereoisomer in high overall yield from 34 . Our convergent strategy enabled us to construct the 14‐membered macrolactone core structure of 2 in a rapid and efficient manner. Total synthesis and biological evaluation of synthetic intermediates and designed synthetic analogues, performed to establish the structure–activity relationships of 2 , led to the discovery of a structurally simple yet potent cytotoxic analogue, 9‐demethylneopeltolide ( 54 ).     

Total synthesis and complete stereostructure of gambieric acid A

Total synthesis of gambieric acid A, a potent antifungal polycyclic ether metabolite, has been accomplished for the first time, which firmly established the complete stereostructure of this natural product.     

Total Synthesis and Stereochemical Revision of Iriomoteolide‐2a

Total syntheses of the proposed and correct structures of iriomoteolide‐2a, a cytotoxic marine macrolide natural product with an unusual 23‐membered macrolactone skeleton, have been accomplished for the first time. The synthesis of the correct structure involves an asymmetric epoxidation/diepoxide cyclization cascade for the construction of the bis(tetrahydrofuran) moiety, a Suzuki–Miyaura coupling for the fragment assembly, and a ring‐closing metathesis for the closure of the macrocyclic backbone. In addition, the original stereochemical assignment of iriomoteolide‐2a was revised.     

A simple,quick and novel protocol for biaryl synthesis using LiCl‐promoted in situ‐generated Pd nanoparticles

This paper describes a simple and a very quick protocol for biaryl synthesis using the Suzuki–Miyaura cross‐coupling reaction. A quintessential role of salting‐out agent LiCl was observed in the Suzuki–Miyaura cross‐coupling reaction that enhanced the reduction rate of Pd (II) to a considerable extent, resulting in the formation of nanosized palladium in a few seconds. The isolated Pd nanoparticles were characterized with X‐ray diffraction, dynamic light scattering, TGA, transmission electron microscopy and scanning electron microscopy‐dispersive X‐ray spectroscopy. The Suzuki–Miyaura cross‐coupling reaction proceeded very well with the in situ‐generated Pd nanocatalysts furnishing the desired biaryl adducts with excellent yields.     

Desulfonative pd‐catalyzed coupling of aryl trifluoroborates with arylsulfonyl chlorides

A Pd‐catalyzed cross‐coupling of aryl trifluoroborates with arylsulfonyl chlorides has been successfully achieved. This transformation is a new method for the Suzuki–Miyaura‐type reaction of aryl trifluoroborates via the cleavage of C? S bond, thus providing an alternative synthesis of biaryls. The reported cross‐coupling reactions are tolerant to many common functional groups regardless of electron‐donating or electron‐withdrawing nature, making these transformations attractive alternatives to the traditional Suzuki–Miyaura coupling approaches. Copyright © 2016 John Wiley & Sons, Ltd.     

Total Synthesis of the Tiacumicin B (Lipiarmycin A3/Fidaxomicin) Aglycone

Tiacumicin B (lipiarmycin A3, fidaxomicin) is an atypical macrolide antibiotic which is used for the treatment of Clostridium difficile infections. Tiacumicin B is also a potent inhibitor of Mycobacterium tuberculosis, but due to its limited oral bioavailability is unsuitable for systemic therapy. To provide a basis for structure–activity studies that might eventually lead to improved variants of tiacumicin B, we have developed an efficient approach to the synthesis of the tiacumicin B aglycone. The synthesis features a high‐yielding intramolecular Suzuki cross‐coupling reaction to effect macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one‐pot Corey–Peterson olefination and an ene–diene cross‐metathesis reaction. Depending on the reaction conditions, the final deprotection delivered either the fully deprotected tiacumicin B aglycone or partially protected versions thereof.     

Studies toward the total synthesis of gambieric acids: convergent synthesis of the GHIJ-ring fragment having a side chain

A stereocontrolled synthesis of the GHIJ-ring fragment having a side chain of gambieric acids, which are potent antifungal polycyclic ether natural products, has been achieved. The synthesis features convergent assembly of the tetracyclic polyether skeleton by using aldol coupling and stereoselective construction of the J-ring side chain by a cerium chloride-promoted Julia-Kocienski reaction.     

Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of a fully elaborated GHIJ-ring fragment

A stereocontrolled synthesis of a fully elaborated GHIJ-ring fragment of gambieric acids, which are potent antifungal polycyclic ether natural products, has been accomplished. The synthesis features convergent assembly of the tetracyclic polyether skeleton through aldol coupling/cyclodehydration/reductive etherification processes and stereoselective construction of the J-ring side chain by a CeCl₃-promoted Julia-Kocienski olefination.     

A green synthesis of palladium nanoparticles by Sapindus mukorossi seed extract and use in efficient room temperature Suzuki–Miyaura cross‐coupling reaction

A simple and green method for the synthesis of palladium nanoparticles using an aqueous extract of Sapindus mukorossi seed has been demonstrated. The synthesized nanoparticles were characterized using UV–visible spectroscopy, powxder X‐ray diffraction, energy‐dispersive X‐ray analysis and transmission electron microscopy. The nanocatalyst was successfully utilized in an efficient Suzuki–Miyaura cross‐coupling reaction at room temperature.     

Synthesis of Thiophene‐Based π‐Conjugated Oligomers via Ligand‐Enabled Pd‐Catalyzed Suzuki–Miyaura Coupling of Haloterthienyls

A ligand‐enabled Pd‐catalyzed Suzuki–Miyaura coupling of haloterthienyls for the synthesis of various thiophene‐based π‐conjugated oligomers including quinquethiophenes is demonstrated. An indolyl phosphine ligand plays an important role in this transformation. Thiopheneboronic acids were well applied, which might open up a window for the application of thiopheneboronic acids in the synthesis of thiophene‐based π‐conjugated oligomers in materials chemistry.     

A highly active palladium(II)–bis(oxazoline) catalyst for Suzuki–Miyaura,Mizoroki–Heck and sonogashira coupling reactions in aqueous dimethylformamide

An efficient catalytic system based on a new palladium–bis(oxazoline) ( Pd-BOX-1 ) complex has been developed. The complex Pd-BOX-1 adopts a legless chair‐type structure where the distorted square planar [PdN₂Cl₂] moiety and the benzene ring spacer represent the seat and the chair back, respectively. The catalytic activity of Pd-BOX-1 has been investigated in dimethylformamide–water under aerobic and mild conditions in Suzuki–Miyaura coupling reactions of arylboronic acids with aryl iodides, aryl bromides and aryl chlorides, Mizoroki–Heck coupling reactions of aryl halides with styrene derivatives, and Sonogashira coupling reactions of aryl halides with terminal alkynes. A wide range of functional groups as substituents on the arylboronic acids and aryl halides were considered. Pd-BOX-1 demonstrates exceptional air and moisture stability. Of note, the catalyst system based on Pd-BOX-1 shows high recycling ability in Suzuki–Miyaura coupling reactions in dimethylformamide–water without any loss in catalytic activity. Copyright © 2015 John Wiley & Sons, Ltd.     

Polyaniline‐anchored palladium catalyst‐mediated Mizoroki–Heck and Suzuki–Miyaura reactions and one‐pot Wittig–Heck and Wittig–Suzuki reactions

A polyaniline‐anchored palladium catalyst was prepared and screened for coupling reactions of aryl halides. The robust and recyclable catalyst was effective in Mizoroki–Heck and Suzuki–Miyaura reactions of aryl bromides and aryl iodides. The catalyst system was further employed for one‐pot Wittig–Heck and Wittig–Suzuki combinations to build conjugated compounds in good conversions. Copyright © 2014 John Wiley & Sons, Ltd.     

Syntheses of the Hexahydroindene Cores of Indanomycin and Stawamycin by Combinations of Iridium‐Catalyzed Asymmetric Allylic Alkylations and Intramolecular Diels–Alder Reactions

Short and concise syntheses of the hexahydroindene cores of the antibiotics indanomycin (X‐14547 A) and stawamycin are presented. Key methods used are an asymmetric iridium‐catalyzed allylic alkylation, a modified Julia olefination, a Suzuki–Miyaura coupling, and an intramolecular Diels–Alder reaction.     

Highly efficient polymer‐stabilized palladium heterogeneous catalyst: Synthesis,characterization and application for Suzuki–Miyaura and Mizoroki–Heck coupling reactions

A suitable approach to stabilize palladium nanoparticles (Pd NPs), with an average diameter of 3–4 nm, on magnetic polymer is described. A new magnetic polymer containing 4′‐(4‐hydroxyphenyl)‐2,2′:6′,2″‐terpyridine (HPTPy) ligand was prepared by the polymerization of itaconic acid (ITC) as a monomer and trimethylolpropane triacrylate (TMPTA) as a cross‐linker and fully characterized. Pd NPs embedded on the magnetic polymer were successfully applied in Suzuki–Miyaura and Mizoroki–Heck coupling reactions under low palladium loading conditions, and provided the corresponding products with excellent yields (up to 98%) and high catalytic activities (TOF up to 257 hr^?1). Also, the catalyst can be easily separated and reused for at least consecutive five times with a small drop in catalytic activity.     

Synthesis,microwave‐promoted catalytic activity in Suzuki–Miyaura cross‐coupling reactions and antimicrobial properties of novel benzimidazole salts bearing trimethylsilyl group

A mixture of benzimidazole salts (2–7), Pd(OAc)₂ and K₂CO₃ in DMF–H₂O catalyzes the Suzuki–Miyaura cross‐coupling reactions promoted by microwave irradiation resulting in high yield within a short time. In particular, the yield of the Suzuki–Miyaura reactions with aryl bromides was found to be nearly quantitative. The synthesized benzimidazole salts (2–7) were identified by ¹H‐¹³C, NMR, IR spectroscopic methods and microanalysis. The molecular structure of 1 was determined by X‐ray crystallography. The antibacterial and antifungal activities of the novel benzimidazole derivatives (1–7) were also tested against standard strains. Copyright © 2011 John Wiley & Sons, Ltd.     

Chemoselective one‐pot synthesis of terphenyl derivatives by sequential directed C―H functionalization–Suzuki coupling

A simple and efficient route for the preparation of terphenyl derivatives via palladium‐catalyzed sequential directed C―H arylation/Suzuki–Miyaura cross‐coupling in ‘one‐pot’ has been developed. 4,4′‐(Cyclohexane‐1,1‐diyl)diphenol is an essential ligand. This reaction can tolerate a series of functional groups and provides the terphenyl derivatives in moderate to good yield. Copyright © 2014 John Wiley & Sons, Ltd.     

Rational Design of an Iron‐Based Catalyst for Suzuki–Miyaura Cross‐Couplings Involving Heteroaromatic Boronic Esters and Tertiary Alkyl Electrophiles

Suzuki–Miyaura cross‐coupling reactions between a variety of alkyl halides and unactivated aryl boronic esters using a rationally designed iron‐based catalyst supported by β‐diketiminate ligands are described. High catalyst activity resulted in a broad substrate scope that included tertiary alkyl halides and heteroaromatic boronic esters. Mechanistic experiments revealed that the iron‐based catalyst benefited from the propensity for β‐diketiminate ligands to support low‐coordinate and highly reducing iron amide intermediates, which are very efficient for effecting the transmetalation step required for the Suzuki–Miyaura cross‐coupling reaction.     

Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C−H Arylation/Ring‐Transformation Strategy

We have described a C?H arylation/ring‐transformation strategy for the synthesis of triarylpyridines, which form the core structure of thiopeptide antibiotics. This synthetic method readily gave 2,3,6‐triarylpyridines in a regioselective manner by a two‐phase approach: C?H arylation (a nickel‐catalyzed decarbonylative Suzuki–Miyaura cross‐coupling and decarbonylative C?H coupling for the synthesis of 2,4‐diaryloxazoles) and ring transformation ([4+2] cycloaddition of 2,4‐diaryloxazoles with (hetero)arylacrylic acids). To showcase these methods, we have accomplished the formal synthesis of thiopeptide antibiotics GE2270 s and amythiamicins.     

A highly efficient heterogeneous montmorillonite K‐10‐supported palladium catalyst for Suzuki–Miyaura cross‐coupling reaction in aqueous medium

A heterogeneous montmorillonite K‐10‐supported palladium triphenylphosphine catalyst is reported for the Suzuki–Miyaura cross‐coupling reaction at room temperature. A library of electronically diverse aryl bromides and arylboronic acids underwent the cross‐coupling reaction at very good rates in aqueous solvent. The reusability of the catalyst was also examined and it was found to be effective up to three catalytic cycles. Copyright © 2014 John Wiley & Sons, Ltd.     

Mechanistic Investigation of Catalyst‐Transfer Suzuki–Miyaura Condensation Polymerization of Thiophene–Pyridine Biaryl Monomers with the Aid of Model Reactions

We have investigated the requirements for efficient Pd‐catalyzed Suzuki–Miyaura catalyst‐transfer condensation polymerization (Pd‐CTCP) reactions of 2‐alkoxypropyl‐6‐(5‐bromothiophen‐2‐yl)‐3‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)pyridine ( 12 ) as a donor–acceptor (D –A) biaryl monomer. As model reactions, we first carried out the Suzuki–Miyaura coupling reaction of X–Py–Th–X′ (Th=thiophene, Py=pyridine, X, X′=Br or I) 1 with phenylboronic acid ester 2 by using tBu₃PPd⁰ as the catalyst. Monosubstitution with a phenyl group at Th‐I mainly took place in the reaction of Br–Py–Th–I ( 1 b ) with 2 , whereas disubstitution selectively occurred in the reaction of I–Py–Th–Br ( 1 c ) with 2 , indicating that the Pd catalyst is intramolecularly transferred from acceptor Py to donor Th. Therefore, we synthesized monomer 12 by introduction of a boronate moiety and bromine into Py and Th, respectively. However, examination of the relationship between monomer conversion and the M_n of the obtained polymer, as well as the matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectra, indicated that Suzuki–Miyaura coupling polymerization of 12 with (o‐tolyl)tBu₃PPdBr initiator 13 proceeded in a step‐growth polymerization manner through intermolecular transfer of the Pd catalyst. To understand the discrepancy between the model reactions and polymerization reaction, Suzuki–Miyaura coupling reactions of 1 c with thiopheneboronic acid ester instead of 2 were carried out. This resulted in a decrease of the disubstitution product. Therefore, step‐growth polymerization appears to be due to intermolecular transfer of the Pd catalyst from Th after reductive elimination of the Th‐Pd‐Py complex formed by transmetalation of polymer Th–Br with (Pin)B–Py–Th–Br monomer 12 (Pin=pinacol). Catalysts with similar stabilization energies of metal–arene η²‐coordination for D and A monomers may be needed for CTCP reactions of biaryl D–A monomers.