Highly functionalized complex molecules are key tools for promoting biochemical research and developing pharmaceuticals, because the network of chiralities, positions of heteroatoms, and direction of lone-pairs in the molecules are strictly linked to their biological activities. Catalytic asymmetric synthesis is the basis and core technology to supply these complex compounds in a stereoselective manner. Here, the catalytic asymmetric [3+2]-cycloaddition of iminoesters and nitroalkenes has been intensively investigated for giving chiral pyrrolidine structures which are observed abundantly in natural products and pharmaceuticals. Although the endo- or exo-selective [3+2]-cycloaddition has been widely examined using chiral Cu-catalysts, there is no report on the catalytic asymmetric synthesis of exo’-adduct. We accomplished the first catalytic asymmetric exo’-selective [3+2]-cycloaddition of azomethine imines and nitroalkenes using imidazoline-aminophenol (IAP)-Ni(OAc)2 complex to give the exo’-adduct in up to 99% ee. The first catalytic asymmetric exo’-selective [3+2]-cycloaddition of methyleneindolinones with iminoesters was also achieved by the IAP-Ni(OAc)2 complex for the construction of a novel diastereomer of biologically important spiro[pyrrolidin-3,3’-oxindole]. Moreover, a novel C2-symmetric bis(imidazolidine)pyridine ligand (PyBidine) was easily synthesized in a single condensation of 2,6-pyridyl aldehyde and optically active (S,S)-diphenylethylene diamine. The newly developed PyBidine-Cu(OTf)2 complex enabled the highly endo-selective [3+2]-cycloaddition of iminoesters with nitroalkenes.
Organofluorine compounds have been receiving significant interest in materials science and medicinal chemistry. Addition reactions of perfluoroalkyl iodide to carbon-carbon double bonds are efficient and versatile for the direct introduction of a perfluoroalkyl group onto organic molecules. However studies on the addition of the perfluoroalkyl radical to electron-deficient olefins are scarce, despite the versatility of the products as fluorine-containing building blocks or monomers. Thus, a novel, efficient perfluoroalkylation of electron-deficient olefins is desirable. Recently, we have developed the effective radical hydroxyperfluoroalkylation, iodoperfluoroalkylation and hydroperfluoroalkynation of electron deficient olefins. We report here these new radical perfluoroalkylations of electron deficient olefines and the diastereoselective reactions using chiral auxiliary method. We also describes the synthesis of chiral fluorinated amino acids and peptides based on these reactions.
Although acetals are useful protective groups for carbonyl functions and widely used in organic synthesis, their protection and deprotection under acidic conditions unable to use the substrates with acid labile functions. We recently found that the combination of TESOTf (Et3SiOTf)—2,6-lutidine or 2,4,6-collidine was effective for the deprotection of acetal. The reaction proceeded under nearly neutral conditions and was applicable to the substrates with acid labile functions, and the most noteworthy of this method is the achievement of the chemoselective deprotection of acetals in the presence of ketals. The above reaction proceeds via pyridinium-type salt intermediates, which are found to be highly reactive toward various nucleophiles not only H2O but also heteroatom and carbon nucleophiles affording the corresponding substituted products. This reaction could be conducted under mild reaction conditions whereas conventional methods need harsh reaction conditions. This methodology is also applicable to the deprotection of acetal-type protective groups such as MOM-type ethers, THP ether, and methylene acetal, and the combination of TMSOTf (TESOTf)—2,2’-bipyridyl afforded the best result.
In recent years, along with growing concern about green chemistry, organocatalysis have been developed as novel catalytic systems due to its metal free nature. Because of their low toxicity and high chemical stability, organocatalysts have increasingly replaced metal catalyzed organic reactions. In particular, ring-opening polymerization (ROP) of cyclic esters, cyclic carbonates, and epoxides proceeded in a controlled/living fashion with organocatalysts. Previously, Hedrick and Waymouth mainly reported various basic or nucleophilic catalysts for ROP of lactide, lactones and trimethylene carbonate. In addition, we newly revealed organic super bases are suitable catalysts for ROP of epoxides. On the other hand, we and some other researchers investigated Brønsted acid catalysts to produce polyester or polycarbonate. In this review, we introduce our and their challenges for ROP using organocatalysts.
The transition metal catalyzed addition reactions of organic electrophiles to activated alkenes, imines and carbonyl compounds are powerful tools for new carbon-carbon bonds with high enantioselectivity. Chiral bidentate phosphoramidite ligands (Me-BIPAM and N-Me-BIPAM) were synthesized from linked-BINOL as new ligands for asymmetric addition reactions of arylboronic acids. These bidentate phosphoramidite ligands appear to be highly effective for rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to α,β-unsaturated ketones. In the course of our study on bidentate phosphoramidites as a chiral ligand for enantioselective bond-forming reactions, we found that N-Me-BIPAM is effective for arylation of N-sulfonyl arylimines with arylboronic acids. Me-BIPAM was found to be highly efficient for ruthenium-catalyzed enantioselective arylation of aldehydes, α-ketoesters, glyoxylate, and isatins. In this review, we focus on chiral bidentate phosphoramidite ligands (Me-BIPAM and N-Me-BIPAM) for asymmetric carbon-carbon bond-forming reactions of arylboronic acids.
Organicboronic acids are commonly used in organic synthesis, although unstable boronic acids are known to decompose competitively in the cross coupling reaction. Recently Burke developed a novel organoboron strategy that allows for the control of cross coupling reaction by using N-methyliminodiacetic acid (MIDA) as boron-protecting group. In this review, the application of MIDA boronate for total syntheses of natural product and the novel development of sp3 hybridized boronate chemistry are described.