Fluorinated organic compounds have received increasing attention due to their unique biological nature in medicinal science and peerlessly excellent property in material science. And thus, a lot of methods for synthesizing highly functionalized fluorinated organic compounds and a number of suitably designed fluorinating reagents have been developed in recent years, most of which have been well documented in excellent reviews and books. However, no review on unique utilization of fluorine(F2) for functionalizing or synthesizing fluorine-free organic compounds has been published. This review involves the fluorine-promoted functionalizations such as oxidations of thiophenes to thiophene S,S-dioxides, pyridines and quinolines to the corresponding N-oxides, and amino group to nitro group along with direct hydroxylation and iodination of aromatics, epoxidation of electron-deficient alkenes, and direct functionalization of 2-position of pyridines. Almost instantaneous oxygen transfer reactions under mild conditions and effective generations of hydoxylium and iodonium ion equivalents otherwise impossible characterize the fluorine-promoted functionalizations.
Addition reaction of heteroatom compounds to carbon-carbon unsaturated bonds based on the cleavage of heteroatom-heteroatom single bonds is one of the most useful and basic methods for selective introduction of heteroatom functional groups into organic molecules. Recently, we have developed addition reactions of tetraphenyldiphosphine bearing P-P single bond to alkynes in the presence of transition metal catalysts or upon photoirradiation. While the photoinduced radical reactions afford the bisphosphination products, the transition-metal-catalyzed reactions give rise to the hydrophosphination products, surprisingly. Based on the combination of tetraphenyldiphosphine and organic dichalcogenides under photoirradiation conditions, we have revealed regioselective addition of both phosphino and chalcogeno groups to carbon-carbon unsaturated bonds.
The chiral bipyridine ligand developed by C. Bolm in 1990 has been revived after 15 years. In this review article, the ring-opening reactions of meso-epoxides with several nucleophiles such as aniline derivatives, alcohols, thiols, indoles, etc. using metal-chiral bipyridine complexes as catalysts are surveyed. Remarkably, the reactions proceeded smoothly in water. For example, in the presence of Sc(III), Zn(II) and Cu(II) surfactant-type catalysts, the ring-opening reactions proceeded smoothly in water to afford the corresponding products in moderate to high yields with good to excellent enantioselectivities. Opposite enantiomers were obtained by using Sc(III) and Zn(II) or Cu(II) with the same chiral bipyridine ligand. Crystal structures of these catalysts may explain the reversal of the enantioselectivity. Some reactions were also tested in dichloromethane (DCM), and it was revealed that the reactions proceeded faster in water than in DCM. Bi(III) and In(III)-chiral bipyridine complexes as chiral catalysts are also discussed.
Tetraorganosilane-type reagents that contain a 2-(hydroxymethyl)phenyl group are invented for silicon-based cross-coupling and carbonyl addition reactions. According to the reagent design, a proximal hydroxy group allows transmetallation of organic groups on silicon with palladium(II), copper(I or II), or rhodium(I) to participate in various transition metal-catalyzed C-C bond forming reactions under mild conditions with excellent chemoselectivity. High stability of the newly developed tetraorganosilicon reagents is demonstrated by their functionalization under various acidic, basic, and oxidative conditions with the silyl group intact. Moreover, simple control of their reactivity by orthogonal protection/deprotection allows highly efficient synthesis of functional molecules such as oligoarenes through iterative cross-coupling/deprotection sequences.
In this accounts, we describe our recent studies on hydrolysis, alcoholysis, and addition of alcohols to organic molecules. The reactions utilizing water and alcohols as a reagent are one of the most basic and simple reactions. The palladium-catalyzed asymmetric hydrolysis and alcoholysis of vinyl ethers gave valuable axially-chiral 1,1'-bi-2-naphthol and 1,1'-bi-2-phenol derivatives and chiral P-chirogenic compounds in optically active form. The reaction is applied for hydrolytic deallylation of N-allyl amide and allyl esters. The later one was achieved by palladium/ruthenium dual catalysts which is the first example of catalytic irreversible ester hydrolysis. Gold complexes also catalyzed vinyl ether alcoholysis and hydroalkoxylation of olefins. In the later reaction, simple unactivated olefins can be used as substrates and gave the product in 92% yield. The copper-DTBM-SEGPHOS complex catalyzed alcoholysis of azlactones which is the first example showing zero-order kinetic resolution.
There has been a considerable progress in the development of the rhodium(I)-catalyzed carbon-carbon bond forming reactions using organoboronic acids during the past decade. In most cases, the intermediate organorhodium(I) complexes are hydrolyzed without being used for a further reaction despite their potential usefulness for carbon-carbon bond formation. We then envisaged that the intramolecular trapping of the intermediate species might be feasible if an accepting functional group was placed at an appropriate position in the molecule. In this article, we describe various types of cascade reactions triggered by addition of arylrhodium(I) species across alkynes. The resulting alkenylrhodium(I) intermediate subsequently undergoes either (type-i) intramolecular addition across a carbon-heteroatom multiple bond, (type-ii) intramolecular addition across a carbon-carbon multiple bond, or (type-iii) β-oxygen elimination. It is also illustrated that the reactivity order of organorhodium(I) intermediates toward nitriles and esters is opposite to that of organolithium and organomagnesium reagents. The synthetic potential of the rhodium-catalyzed reaction of alkynyl oxiranes with arylboronic acids was demonstrated by applying to the total synthesis of (±)-Boivinianin B.
Despite increasing pharmaceutical importance, fluorinated arenes remain difficult to synthesize. Particularly, developing general methods that enables to introduce fluoride on the aromatic ring at the final stage is of great interest. In this mini review, the recent progress of aromatic fluorination reactions using transition metals will be described.
Science has unveiled tricks hidden in the unique chemical structures and biological activities of naturally occurring compounds. Triggered by these findings, scientists have discovered substances and developed them into new drugs, which have been used in the mid 20th century and beyond to cure the sick. The author recalls his educational research experiences in the chemical synthesis of kanamycin, an antibiotic, in the isolation and structural determination of aplysiatoxin, a marine toxin, and in his corporate research and development of drugs with active forms of vitamin D from the 1960s to the 1980s. Biologically active natural products from marine sources often have highly complex structures. He hopes that in the 21st century the highly advanced organic syntheses will play a key role in the discovery and development of new drugs from marine natural products to treat unmet needs.