Studies of the Electronic Effects of Zinc Cluster Catalysts and Their Application to the Transesterification of β‐Keto Esters

The electronic effects of tetranuclear zinc cluster catalysts on transesterification were investigated by changing the carboxylate ligands in the clusters. High catalyst activity crucially depended on the balance between Lewis acidity and Brønsted basicity of the catalyst; this was consistent with the dual activation of both the electrophile and nucleophile by the cooperative zinc centers. In addition, tetranuclear zinc cluster catalysts achieved the transesterification of β‐keto esters with unprecedented levels of broad substrate generality, in which a newly developed pentafluoropropionate‐bridged zinc cluster and 4‐dimethylaminopyridine additive greatly improved the reactivity of sterically congested α‐ and α,α‐disubstituted β‐keto esters.     

Heterogeneous Pd/C-catalyzed ligand-free, room-temperature Suzuki-Miyaura coupling reactions in aqueous media

A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (<1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis.     

Novel Pd/C-catalyzed redox reactions between aliphatic secondary alcohols and ketones under hydrogenation conditions: application to H-D exchange reaction and the mechanistic study

A liquid-phase redox system between secondary alcohols and ketones is described. Deuteration of either secondary alcohols or ketones using the Pd/C-H2-D2O system gave a mixture of deuterium-labeled secondary alcohols and ketones. The results indicated that the secondary alcohol was oxidized to the corresponding ketone without oxidants under the hydrogenation conditions and the hydrogenation of the aliphatic ketone to the corresponding secondary alcohol simultaneously proceeded. Detailed mechanistic studies on the redox system as well as the H-D exchange reaction are discussed.     

Matrix-assisted laser desorption/ionization mass spectrometry using a visible laser

Visible matrix-assisted laser desorption/ionization (VIS-MALDI) was performed using 2-amino-3-nitrophenol as matrix. The matrix is of near-neutral pH, and has an optical absorption band in the near-UV and visible region. A frequency-doubled Nd:YAG laser operated at 532 nm wavelength was used for matrix excitation and comparisons were made with a frequency-tripled Nd:YAG laser (355 nm). Visible and ultraviolet (UV)-MALDI produce similar mass spectra for peptides, polymers, and small proteins with comparable sensitivities. Due to the smaller optical absorption coefficient of the matrix at 532 nm wavelength, the optical penetration depth is larger, and the sample consumption per laser shot in VIS-MALDI is higher than that of UV-MALDI. Nevertheless, VIS-MALDI using 2-amino-3-nitrophenol as matrix may offer a complementary technique to the conventional UV-MALDI method in applications where deeper laser penetration is required.     

Efficient Generation of Microdroplets Using Tail Breakup Induced with Multi-Branch Channels

In recent years, research on the application of microdroplets in the fields of biotechnology and chemistry has made remarkable progress, but the technology for the stable generation of single-micrometer-scale microdroplets has not yet been established. In this paper, we developed an efficient and stable single-micrometer-scale droplet generation device based on the fragmentation of droplet tails, called “tail thread mode”, that appears under moderate flow conditions. This method can efficiently encapsulate microbeads that mimic cells and chemical products in passively generated single-micrometer-scale microdroplets. The device has a simple 2D structure; a T-junction is used for droplet generation; and in the downstream, multi-branch channels are designed for droplet deformation into the tail. Several 1–2 µm droplets were successfully produced by the tail’s fragmentation; this continuous splitting was induced by the branch channels. We examined a wide range of experimental conditions and found the optimal flow rate condition can be reduced to one-tenth compared to the conventional tip-streaming method. A mold was fabricated by simple soft lithography, and a polydimethylsiloxane (PDMS) device was fabricated using the mold. Based on the 15 patterns of experimental conditions and the results, the key factors for the generation of microdroplets in this device were examined. In the most efficient condition, 61.1% of the total droplets generated were smaller than 2 μm.     

Stable Subporphyrin meso-Aminyl Radicals without Resonance Stabilization by a Neighboring Heteroatom

Most aminyl radicals studied so far are resonance-stabilized by neighboring heteroatoms, and those without such stabilization are usually short-lived. We report herein that subporphyrin meso-2,4,6-trichlorophenylaminyl radicals and a bis(5-subporphyrinyl)aminyl radical are fairly stable under ambient conditions without such stabilization. The subporphyrin meso-2,4,6-trichlorophenylaminyl radical crystal structure displays a characteristically short C_meso−N bond and a perpendicular arrangement of the meso-arylamino group. The stabilities of these radicals have been ascribed to extensive spin delocalization over the subporphyrin π-electronic network as well as steric protection around the aminyl radical center.     

Apical functionalization of chiral heterohelicenes

We describe a synthetic protocol to selectively functionalize chiral bridged triarylamines at the apical position using regioselective copper-catalyzed amination reaction. This protocol allows the coupling of diphenylamines with a sterically hindered but electronically activated aryl-Br bond in the presence of a sterically unhindered but electronically unactivated aryl-Br bond. The unactivated aryl-Br bond was utilized further to synthesize a chiral heterohelicene homodimer using Stille coupling.     

Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH(4)OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.     

Redesign of enzyme for improving catalytic activity and enantioselectivity toward poor substrates: manipulation of the transition state

Secondary alcohols having bulky substituents on both sides of the hydroxy group are inherently poor substrates for most lipases. In view of this weakness, we redesigned a Burkholderia cepacia lipase to create a variant with improved enzymatic characteristics. The I287F/I290A double mutant showed a high conversion and a high E value (>200) for a poor substrate for which the wild-type enzyme showed a low conversion and a low E value (5). This enhancement of catalytic activity and enantioselectivity of the variant resulted from the cooperative action of two mutations: Phe287 contributed to both enhancement of the (R)-enantiomer reactivity and suppression of the (S)-enantiomer reactivity, while Ala290 created a space to facilitate the acylation of the (R)-enantiomer. The kinetic constants indicated that the mutations effectively altered the transition state. Substrate mapping analysis strongly suggested that the CH/π interaction partly enhanced the (R)-enantiomer reactivity, the estimated energy of the CH/π interaction being -0.4 kcal mol(-1). The substrate scope of the I287F/I290A double mutant was broad. This biocatalyst was useful for the dynamic kinetic resolution of a variety of bulky secondary alcohols for which the wild-type enzyme shows little or no activity.