A chiral N,N,N-terdentate bis(imidazolidine)pyridine (PyBidine) has showed remarkable ligand acceleration effects in various metal catalyzed asymmetric reactions. For an example, PyBidine-Cu(OTf)2 catalyzed a highly endo-selective ［3＋2］ cycloaddition of nitroalkenes with imino esters. X-ray crystallographic analysis of the PyBidine-Cu(OTf)2 complex and DFT calculations suggest that an intermediary generated Cu-enolate of the imino ester reacts with nitroalkenes, which are activated by NH-proton of imidazolidine ligand. Based on the intelligent role of imidazolidine, a new chiral imidazolidine-containing NCN palladium pincer complex (tBu-PhBidine-PdX) was prepared by a ligand introduction route. The neutral tBu-PhBidine-PdCl complex demonstrated significant catalytic activity for the reaction of nitroalkenes with malononitrile to give the products in good yields with high enantioselectivities. On the contrary, the cationic chiral imidazolidine-containing tBu-PhBidine-PdOTf catalyst promoted the nucleophilic addition of unprotected indoles to N-Boc imines. Using sulfinyl amines as the N-Boc imine precursors, the combined use of catalyst with K2CO3 activated the N-H-free indoles to give chiral 3-indolyl methanamines with up to 98% ee. Compared with conventional acid-catalyzed Friedel-Crafts reactions, this reaction proceeding under mildly basic conditions shows advantages for the use of acid-sensitive substrates. Furthermore, chiral bis(imidazolidine)-containing PhBidine-Rhodium complexes (PhBidine-RhX2 and tBu-PhBidine-RhX2) were prepared by a C-H insertion method. The tBu-PhBidine-Rh(OAc)2 smoothly catalyzed an asymmetric Mannich reaction of malononitrile with N-Boc imines to give products, which are useful for the synthesis of chiral α-amino acids.
Over the last two decades, transition-metal-catalyzed chelate-assisted direct functionalization of aryl C-H bonds has been well developed. These methodologies realized the efficient carbon-carbon, carbon-oxygen, carbon-nitrogen, and carbon-halogen bond formations. However, the related catalytic direct thiolation and selenation have yet to be disclosed despite the utilities of organosulfur and organoselenium compounds as building blocks in bioactive molecules and functional organic materials. Very recently, several research groups including our group have developed chelate-assisted intermolecular direct thiolation and selenation by using various transition metal catalysts, such as palladium, rhodium, nickel, copper, ruthenium, and cobalt. This article describes our recent studies on chelate-assisted catalytic direct thiolation and selenation of aryl C-H bonds. The reactions with thiols, disulfides, selenols, diselenides, and elemental selenium proceeded well in the presence of palladium or nickel catalyst to provide a variety of organochalcogen compounds. In addition, an appropriate choice of the directing group can be made to control the reaction sites.
Reductive molecular transformations by indium/hydrosilane catalyst systems are described herein. A catalytic reductive molecular transformation using a hydrosilane is an important synthetic tool, because silicon-based reducing reagents are frequently easy to handle and exhibit high chemoselectivity to each functional group, due to their lower reactivity than that of other reducing agents. In order for a hydrosilane to show the potential ability as a valuable reducing agent in organic synthesis, therefore, the appropriate choice of a catalyst is an imperative and a significant matter. We continue to perform the use of indium catalysts as good promoters for a variety of silane-mediated reductive transformations. In this review, we summarized our recent results for indium-catalyzed or-mediated transformations as the following chapters: (i) simple reductions of functional groups, especially for carboxylic acid derivatives; (ii) reductive alkylations at oxygen-, nitrogen-, halogen-, carbon-, and sulfur-atoms, by using carboxylic acids as alkylation reagents; (iii) applied reactions based on the reductive transformations including cyclization and hydroamination; (iv) other type reactions promoted by indium (III) compounds, such as Knoevenagel condensation and oxidative coupling through Oppenauer oxidation.
Recently, π-conjugated molecules with curved-π surface have attracted considerable interest for their unique properties originating from their curved structures. However, most of them consist of only carbon and hydrogen atoms. In these situations, we have developed novel synthetic protocols for construction of distorted structures directly from 2D π-conjugated molecules under mild reaction conditions. By applying phenol and aniline oxidation methods, we have succeeded in the synthesis of highly distorted cyclophanes, π-extended heterohelicenes, and highly twisted porphyrin oligomers. Furthermore, we have succeeded in the synthesis of a nitrogen-embedded buckybowl as a novel bowl-shaped π-conjugated molecule with a pyrrolic nitrogen in its skeleton. These heteroatom containing curved-π conjugated molecules exhibit unique characteristics due to the combination of the curved structure with heteroatoms such as circularly polarized luminescence, strong C60 binding, and near IR electrochromism. We believe that the chemistry of heteroatom containing curved-π conjugated molecules would enhance the potential of three-dimensional π-conjugated molecules for molecular materials.
Intein-mediated protein splicing system is an autocatalytic process in which an intervening protein sequence (intein) excises itself from the intein-embedded polypeptide sequence; concomitantly creating a new peptide bond between its two flanking sequences (exteins). In the intein-mediated protein splicing, sequentially occurring N-S, S-S, and S-N acyl transfers are cornerstone events. Chemical bases involved in such acyl transfer steps have provided insights of great use for developing wide varieties of chemical methodologies for peptide/protein chemistry. Therefore, we have continued our research efforts to develop innovative methodologies for preparation of peptide thioesters on the basis of “Intein Chemistry”. Peptide/protein thioesters have served as an indispensable synthetic intermediate of tremendous use in native chemical ligation (NCL) which has proven extraordinarily powerful for chemical synthesis or semisynthesis of proteins. In this review, we present the development of both N-sulfanylethylanilide (SEAlide) peptides as a crypto-thioester and chemical protocols for thioester preparation applicable to naturally occurring peptide sequences on the basis of the chemistry found in the intein-mediated protein splicing.
Regio- and stereoselective synthesis of organoboron compounds has great importance due to their wide applicability and high stereospecificity in many transformations such as Suzuki-Miyaura cross coupling reaction. Generally, hydroboration of unactivated terminal alkenes proceeds in anti-Markovnikov selective manner to produce linear products. In this short review, recent examples of catalytic Markovnikov hydroboration of unactivated terminal alkenes, and its application to asymmetric synthesis are described.
To date, a large number of transformations utilizing organoboranes have been developed. In this review, electrophile-induced 1,2-metallate rearrangement of alkenyl borates will be focused. Since Zweifel’s pioneering work, a number of reactions utilizing the rearrangement have been reported. Some of the reactions will be presented.
Glycan chains of various glycoconjugates are known to play pivotal roles in biological systems. Given their structural complexity diversity, chemical synthesis is expected to be powerful in understanding functions of glycan chains at molecular level. However, synthesis of glycan chains is more problematic than other biomolecules such as oligopeptides and oligonucleotides, because high efficiency, especially in terms of precise stereocontrol is difficult to achieve. In addition, glycan containing molecules having biological relevance often have highly complex structures. To remove these problems, various studies have been conducted, among which highly significant contributions have been made by researchers in Japan. Based on these, this brief article summarizes recent advances in the synthesis of complex glycans, glycolipids and glycoproteins, along with development of methodologies, made by researchers in Japan.