Synthesis of meso-arylsulfanyl- and alkylsulfanyl-substituted porphyrins via palladium-mediated C-S bond formation

A family of new meso-arylsulfanyl- and alkylsulfanyl-substituted porphyrins were efficiently synthesized from direct reactions of meso-brominated porphyrins with thiols via palladium-mediated C-S bond formation. The catalytic method can be performed under mild conditions with both mono- and bis-substituted meso-bromoporphyrins as well as their zinc complexes and is suitable for different types of thiols. With the use of selenols, meso-seleno-substituted porphyrins can also be prepared similarly.     

Formal synthesis of uvaricin via palladium-mediated double cyclization

[see reaction]. A novel palladium-mediated, ligand-controlled double cyclization is reported. The C2-symmetric diene produced was desymmetrized via Sharpless asymmetric dihydroxylation and was further transformed into a known intermediate in the synthesis of uvaricin.     

Asymmetric synthesis of allylic sulfides via palladium-mediated allylation of thiols

Cyclic and acyclic allylic S-p-chlorophenyl, S-2-pyridyl and S-2-pyrimidyl sulfides of 50–96% ee have been obtained in 24–87% yield through reaction of the corresponding racemic carbonates with p-chlorothiophenol, 2-mercaptopyridine and 2-mercaptopyrimidine, respectively, mediated by a complex generated in situ from Pd₂(dba)₃·CHCl₃ and the Trost ligand.     

Adsorption characteristics of tripodal thiol-functionalized porphyrins on gold

X-ray photoelectron and Fourier transform infrared spectroscopy studies are reported for self-assembled monolayers (SAMs) of two tripodal thiol-functionalized metalloporphyrins (Zn and Cu) and three benchmark tripods on gold substrates. The tripodal unit common to all five molecules is 1-(phenyl)-1,1,1-tris(4-mercaptomethylphenyl)methane (Tpd). Both porphyrins contain S-acetyl-protected thiols and are linked to the 4-position of the phenyl ring of Tpd via a phenylethyne group. The benchmark molecules include (1) two tripods containing a bromine atom at the 4-position of the apical phenyl ring, one a free thiol and the other its S-acetyl-protected analogue, and (2) a S-acetyl-protected tripod containing a phenylethyne unit at the 4-position of the apical phenyl group. Together, the spectroscopic studies reveal that none of the five tripodal molecules bond to the gold surface via all three sulfur atoms. Instead, the average number of bound thiols ranges from 1.5 to 2, with the porphyrinic molecules generally falling at the middle to upper end of the range and the smallest benchmark tripods falling at the lower end. Similar surface binding is found for the S-acetyl-protected and free benchmark tripods, indicating that the presence of the protecting group does not influence binding. Furthermore, the surface binding characteristics of the SAMs are not sensitive to deposition conditions such as solvent type, deposition time, or temperature of the solution.     

Efficient asymmetric synthesis of biologically important tryptophan analogues via a palladium-mediated heteroannulation reaction.

A novel and concise synthesis of optically active tryptophan derivatives was developed via a palladium-catalyzed heteroannulation reaction of substituted o-iodoanilines with an internal alkyne. The required internal alkyne 14a or 25 was prepared in greater than 96% de via alkylation of the Sch?llkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Sch?llkopf chiral auxiliary was chosen here for the preparation of L-tryptophans would be available from D-valine while the D-isomers required for natural product total synthesis would originate from the inexpensive L-valine (300-g scale). Applications of the palladium-catalyzed heteroannulation reaction were extended to the first asymmetric synthesis of L-isotryptophan 38 and L-benz[f]tryptophan 39. More importantly, the optically pure 6-methoxy-D-tryptophan 62 was prepared by this protocol on a large scale (>300 g). This should permit entry into many ring-A oxygenated indole alkaloids when coupled with the asymmetric Pictet-Spengler reaction. In addition, an improved total synthesis of tryprostatin A (9a) was accomplished in 43% overall yield employing this palladium-mediated process.     

Asymmetric synthesis of the balanol heterocycle via a palladium-mediated epimerization and olefin metathesis

[formula: see text] The enantioselective formal synthesis of balanol, a potent protein kinase C inhibitor, was accomplished from D-serine utilizing a Pd-catalyzed equilibration of diastereomeric 5-vinyloxazolines to set the stereochemistry of the vicinal amino and hydroxyl groups. A ruthenium-catalyzed ring-closing metathesis was employed to form the seven-membered nitrogen heterocyle.     

Photophysical properties of unsymmetric meso-substituted porphyrins synthesized via the Suzuki coupling reaction

A new family of porphyrins containing different groups in meso positions was synthesized by Suzuki coupling reaction of meso mono- and dibromo-diarylporphyrins with several boronate esters, catalyzed by palladium organometallic complexes. These procedures gave high yields of unsymmetric porphyrins bearing carboxylate anchoring groups, with enhanced absorptions in the red and showing no tendency for aggregation in toluene or THF solutions. Such properties are of interest for application in dye-sensitized solar cells.     

A concise synthesis of all four possible benzo[4,5]furopyridines via palladium-mediated reactions

[reaction: see text] By taking advantage of the alpha- and gamma-activation of chloropyridines as well as palladium-mediated reactions, all four possible benzo[4,5]furopyridine tricyclic heterocycles, benzo[4,5]furo[2,3-b]pyridine, benzo[4,5]furo[2,3-c]pyridine, benzo[4,5]furo[3,2-c]pyridine, and benzo[4,5]furo[3,2-b]pyridine, are efficiently synthesized from 2-chloro-3-iodopyridine, 3-chloro-4-stannylpyridine, 4-chloro-3-iodopyridine, and 2-chloro-3-hydroxypyridine, respectively.     

Synthesis of arnottin I through a palladium-mediated aryl-aryl coupling reaction

6H-Dibenzo[b,d]pyran-6-one, 6H-benzo[d]naphtho[1,2-b]pyran-6-one, and their derivatives were prepared via the palladium mediated aryl-aryl coupling reaction of aryl ortho-halobenzoate. The short step synthesis of arnottin I(1) was achieved by this method.     

Biaryl synthesis via palladium-catalyzed aryne multicomponent coupling

Aryl iodides have been introduced as electrophiles in the three-component Heck coupling of arynes. Following optimization studies to favor three- versus two-component coupling, the reaction proceeds in good yield to afford a variety of functionalized biaryls.     

Total synthesis of hydroxystrobilurin A via Stille coupling

A six-step total synthesis of the fungicidal natural product hydroxystrobilurin A is described, utilising Stille chemistry for efficient access to the strobilurin (E,Z,E)-triene system.     

An expedient synthesis of ellipticine via Suzuki-Miyaura coupling

A simple and efficient total synthesis of ellipticine was developed via the Suzuki-Miyaura coupling of sterically sensitive 2-hydroxybenzeneboronic acid with a multifunctional aryl halide using Pd(OAc)₂ as a catalyst and Cu(OAc)₂·H₂O as an additive in DMSO/H₂O as a key step followed by double N-arylation and cyclization.     

Facile and efficient synthesis of meso-arylamino- and alkylamino-substituted porphyrins via palladium-catalyzed amination

meso-Arylamino- and alkylamino-substituted porphyrins were efficiently synthesized by reactions of meso-halogenated porphyrins with amines via palladium-catalyzed amination. The combination of palladium acetate and the commercially available phosphine ligand bis(2-diphenylphosphinophenyl) ether (DPEphos) is effective for catalyzing the couplings of both [5-bromo-10,20-diphenyl porphyrino]zinc(II) and [5,15-dibromo-10,20-diphenylporphyrino]zinc(II) with amines to give the corresponding monoamino- and diamino-substituted porphyrins in high yields under mild conditions. The corresponding halogenated free-base porphyrins also underwent the cross-coupling reactions efficiently under similar catalytic conditions.     

Versatile synthesis of meso-aryloxy- and alkoxy-substituted porphyrins via palladium-catalyzed C-O cross-coupling reactions

[reaction: see text] meso-Aryloxy- and alkoxy-substituted porphyrins were conveniently synthesized by direct reactions of meso-halogenated porphyrins with alcohols via palladium-catalyzed C-O cross-coupling reactions. Using a combination of palladium precursor Pd(OAc)(2) or Pd(2)(dba)(3) and phosphine ligand DPEphos or Xantphos allowed both 5-bromo-10,20-diarylporphyrin and 5,15-dibromo-10,20-diarylporphyrin, as well as their zinc complexes, to be effectively coupled with a variety of alcohols to give the corresponding mono- and bis-substituted meso-aryloxy/alkoxyporphyrins in moderate to high yields under mild conditions.     

Heterocycle synthesis via direct C-H/N-H coupling

A method for five- and six-membered heterocycle formation by palladium-catalyzed C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)(2) oxidant, and toluene solvent at 80-120 °C. Cyclization is effective for sp(2) as well as aliphatic and benzylic sp(3) C-H bonds.     

A compact all-carbon tripodal tether affords high coverage of porphyrins on silicon surfaces

[Structure: See text] Redox-active molecules designed to give high charge density on electroactive surfaces are essential for applications in molecular information storage. To achieve a small molecular footprint and thereby high surface charge density, a compound consisting of a triallyl tripod attached via a p-phenylene unit to a porphyrin (1) has been synthesized. The zinc chelate of 1 (Zn-1) was attached to Si(100). Electrochemical measurements indicate that the molecular footprint (75 A) in the monolayer is only approximately 50% larger than the minimum achievable, indicating high surface coverage. IR spectroscopy indicates that the bands due to the nu(C=C) (1638 cm(-1)) and gamma(CH) (915 cm(-1)) vibrations present in the solid sample (KBr pellet) are absent from the spectra of the monolayers of Zn-1, consistent with saturation of the double bond in each of the three legs of the tripod upon the hydrosilylation process accompanying attachment. Comparison of the relative intensities of the in-plane (998 cm(-1)) versus out-of-plane (797 cm(-1)) porphyrin modes indicates the average tilt angle (alpha) of the porphyrin ring with respect to the surface normal is approximately 46 degrees , a value also observed for analogous porphyrins tethered to Si(100) via monopodal carbon linkers. Accordingly, the higher packing densities afforded by the compact tripodal linker are not due to a more upright orientation on the surface. The charge-retention half-lives (t1/2) for the first oxidation state of the Zn-1 monolayers increase from 10 to 50 s at low surface coverage (1-5 x 10(-11) mol.cm(-2)) to near 200 s at saturation coverage (approximately 2 x 10(-10) mol.cm(-2)). Taken together, the high surface charge density (despite the lack of upright orientation) of the triallyl-tripodal porphyrin makes this construct a viable candidate for molecular information storage applications.     

The synthesis of substituted phenylpyrimidines via suzuki coupling reactions

This paper describes the mon‐, di‐, and triarylation of the pyrimidine ring. It is possible to introduce one or more aryl rings in generally good yields and in a specific order, namely first in position 4, second in position 6, followed by position 2. A study of solvent and catalyst requirements has also been conducted.     

Microwave-assisted synthesis of salicylamide via BCl3 mediated coupling

A novel and efficient microwave-assisted, BCl3-mediated coupling reaction to synthesize salicylamide structures from phenols and isocyanates is described.     

Concise total synthesis of honokiol via Kumada cross coupling

A concise four-step efficient synthesis of honokiol 1 in 68% overall yield is described here. The present method involves tetrakis(triphenylphosphine)palladium [Pd(Ph₃)₄] catalyzed Kumada coupling in two key steps. First coupling generates biaryl backbone intermediate 5 and second generates 2,4′-O-dimethylhonokiol 3. Final demethylation under AlCl₃/DMS condition affords honokiol in quantitative yield.     

Palladium-catalyzed synthesis of indole fused coumarins via cross-dehydrogenative coupling

The present method describes a palladium-catalyzed cross-dehydrogenative coupling reaction of coumarin and aniline for the synthesis of indole fused coumarin derivatives. The one-pot method is operationally simple and molecular oxygen is used as sole oxidant. The target compounds are obtained in good yields from commercially available precursors.