Preparation of benzolactams by Pd(OAc)2-catalyzed direct aromatic carbonylation

We developed a new method for Pd(II)-catalyzed direct aromatic carbonylation in a phosphine-free catalytic system using Pd(OAc)2 and Cu(OAc)2 in an atmosphere of CO gas containing air. The carbonylation proceeded with ortho-palladation, inducing a remarkable site selectivity to afford a variety of five- or six-membered benzolactams from secondary omega-arylalkylamines, such as N-alkylbenzylamines or N-alkylphenethylamines.     

Ammonium bromides/KF catalyzed trifluoromethylation of carbonyl compounds with (trifluoromethyl)trimethylsilane and its application in the enantioselective trifluoromethylation reaction

The trifluoromethylation of aldehydes and ketones is a potentially powerful method to introduce the CF₃ moiety into organic molecules. In general, the trifluoromethylation reaction has been performed by treatment of Me₃SiCF₃ under initiation by TBAF, TBAT, TMAF as well as CsF. However, these commercially available fluorides are rather expensive and moisture sensitive. Potassium fluoride (KF) is an inexpensive and commonly used fluoride source and can be also used as an initiator for the trifluoromethylation, but the method suffers from the significant limitation that only DMF is available as a solvent. Therefore, novel methods are highly desirable for laboratory-scale as well as large-scale preparations. Here we wish to report a convenient procedure where a KF/TBAB combination acts as a catalyst for trifluoromethylation of aldehydes, ketones, and imides in a variety of organic solvents to provide trimethylsilyl-protected α-trifluoromethyl alcohols in good to high yields. Application of the method in the enantioselective trifluoromethylation is also discussed.     

Interlayer Reaction of Polyamine/α-Zirconium Phosphate Intercalation Compounds with Some Aldehydes

Abstract

The intercalation compound between α-zirconium phosphate and N,N′-bis-(3-aminopropyl)-1, 3-propanediamine has two different modifications with respect to the conformation of the guest amine molecules: one is “bent form” and the other “straight form”. Reactivity of each phase with a series of aldehydes was examined. ¹³C CP/MAS NMR indicated that the tetraamine reacts stereoselectively with aldehydes to form cis-imine in the interlayer spacing. Depending on the molecular size of aldehyde, it is found that a significant difference can be recognized in the yields of the imine products for the two phases of intercalation compounds. It is also noted that residual water molecules in the interlayer spacing play an important role in the imine formation reaction.     

Total Synthesis and Functional Evaluation of Fourteen Derivatives of Lysocin E: Importance of Cationic,Hydrophobic, and Aromatic Moieties for Antibacterial Activity

Lysocin E ( 1 ) is a structurally complex 37‐membered depsipeptide comprising 12 amino‐acid residues with an N‐methylated amide and an ester linkage. Compound 1 binds to menaquinone (MK) in the bacterial membrane to exert its potent bactericidal activity. To decipher the biologically important functionalities within this unique antibiotic, we performed a comprehensive structure‐activity relationship (SAR) study by systematically changing the side‐chain structures of l ‐Thr‐1, d ‐Arg‐2, N‐Me‐d ‐Phe‐5, d ‐Arg‐7, l ‐Glu‐8, and d ‐Trp‐10. First, we achieved total synthesis of the 14 new side‐chain analogues of 1 by employing a solid‐phase strategy. We then evaluated the MK‐dependent liposomal disruption and antimicrobial activity against Staphylococcus aureus by 1 and its analogues. Correlating data between the liposome and bacteria experiments revealed that membrane lysis was mainly responsible for the antibacterial functions. Altering the cationic guanidine moiety of d ‐Arg‐2/7 to a neutral amide, and the C7‐acyl group of l ‐Thr‐1 to the C2 or C11 counterpart decreased the antimicrobial activities four‐ or eight‐fold. More drastically, chemical mutation of d ‐Trp‐10 to d ‐Ala‐10 totally abolished the bioactivities. These important findings led us to propose the biological roles of the side‐chain functionalities.     

Pd(OAc)2-catalyzed carbonylation of amines

A phosphine-free catalytic system [Pd(OAc)2-Cu(OAc)2-air] induced a substrate-specific carbonylation of amines in boiling toluene under CO gas (1 atm). Symmetrical N,N'-dialkylureas were obtained by the carbonylation of primary amines. N,N,N'-Trialkylureas were selectively formed by addition of a secondary amine to the above reaction vessel. Secondary amines did not give tetraalkylureas. However, dialkylamines with a phenyl group on their alkyl chains, such as N-monoalkylated benzylic amine or phenethylamine derivatives, underwent a direct aromatic carbonylation to afford five- or six-membered benzolactams. In the carbonylation, the chelation effect or steric repulsion between Pd(II) and the meta-substituent in the ortho-palladation and the ring sizes of cyclopalladation products that were formed prior to carbonylation were found to generate good site selectivity and increase the reaction rate. In contrast, carbonylation of omega-arylalkylamines with a hydroxyl group gave neither ureas nor benzolactams but instead produced 1,3-oxazolidinones smoothly. Hydrochlorides of amines also underwent carbonylation to afford the corresponding amides under the conditions used. This procedure made it possible to prepare ureas of amino acid esters and N-alkylcarbamates in practical yields.     

Unprecedented formation of a rhodium cluster triggered by rhodium-fastened N-confused gable porphyrin

Thermal reaction of N-confused porphyrin (NCP) with [RhCl(CO)2]2 caused unprecedented formation of tetranuclear rhodium complex Rh4(NCP)2(CO)4 having a gable-porphyrin-type structure, where two porphyrin pi systems were electronically connected by the rhodium cluster.     

Formation and characterization of emulsions using beta-cyclodextrin as an emulsifier

The preparation and characterization of n-alkane/water emulsions using beta-cyclodextrin (beta-CD) were studied. The prepared n-alkane/water emulsions were of the oil-in-water (O/W) type, and the stability of emulsions was in the order of n-hexadecane > n-dodecane > n-octane. From observations using polarized light microscopy and powder X-ray diffraction measurement, it was suggested that the formation of a dense film at the oil-water interface and the three-dimensional structural network created by precipitated complexes in the continuous phase are associated with the stability of emulsion. Furthermore, it was clarified that O/W-type emulsions were formed because the contact angle (theta ow) which the precipitate makes with the interface was theta ow < 90 degrees in all compounds (oils) used in this study.     

Synthesis, reactivity, and properties of N-fused porphyrin rhenium(I) tricarbonyl complexes

The thermal reactions of N-fused tetraarylporphyrins or N-confused tetraarylporphyrins with Re2(CO)10 gave the rhenium(I) tricarbonyl complexes bearing N-fused porphyrinato ligands (4) in moderate to good yields. The rhenium complexes 4 are characterized by mass, IR, 1H, and 13C NMR spectroscopy, and the structures of tetraphenylporphynato complex 4a and its nitro derivative 15 are determined by X-ray single crystal analysis. The rhenium complexes 4 show excellent stability against heat, light, acids, bases, and oxidants. The aromatic substitution reactions of 4 proceed without a loss of the center metal to give the nitro (15), formyl (16), benzoyl (17), and cyano derivatives (19), regioselectively. In the electrochemical measurements for 4, one reversible oxidation wave and two reversible reduction waves are observed. Their redox potentials imply narrow HOMO-LUMO band gaps of 4 and are consistent with their electronic absorption spectra, in which the absorption edges exceed 1000 nm. Theoretical study reveals that the HOMO and LUMO of the rhenium complexes are exclusively composed of the N-fused porphyrin skeleton. Protonation of 4 takes place at the 21-position regioselectively, reflecting the high coefficient of the C21 atom in the HOMO orbital. The skeletal rearrangement reaction from N-confused porphyrin Re(I) complex (8) to N-fused porphyrin Re(I) complex (4) is suggested from the mechanistic study as well as DFT calculations.     

Silylation Improves the Photodynamic Activity of Tetraphenylporphyrin Derivatives In Vitro and In Vivo

The effects of silyl and hydrophilic groups on the photodynamic properties of tetraphenylporphyrin (TPP) derivatives have been studied in vitro and in vivo. Silylation led to an improvement in the quantum yield of singlet oxygen sensitization for both sulfo and carboxy derivatives, although the silylation did not affect other photophysical properties. Silylation also improved the cellular uptake efficiency for both sulfo and carboxy derivatives, enhancing the in vitro photodynamic activity of the photosensitizer in U251 human glioma cells. The carboxy derivative (SiTPPC₄) was found to show higher cellular uptake efficiency and in vitro photodynamic activity than the corresponding sulfo derivative (SiTPPS₄), which indicates that the carboxy group is a more promising hydrophilic group than the sulfo group in the silylated porphyrin. SiTPPC₄ was found to show high selective accumulation efficiency in tumors, although almost no tumor selectivity was observed for the nonsilylated porphyrin. The concentration of SiTPPC₄ in tumors was 13 times higher than that in muscle 12 h after drug administration. We also studied tumor response after treatment and found that silylation enhanced in vivo photodynamic activity significantly. SiTPPC₄ shows higher photodynamic activity than NPe6 with white light irradiation.     

Diels‐alder reaction of 1‐methyl‐3,6,8‐trinitro‐2‐quinolone

1‐Methyl‐3,6,8‐trinitro‐2‐quinolone (1) behaved as the dienophile in Diels‐Alder reactions with dienes. When cyclopentadiene was used, cycloadduct 4 was obtained, which was then aromatized on treatment with triethylamine. In the reaction of 1 with hydrazone of 2‐butenal, phenanthridine derivative 7 was produced.