New boron-based reactions utilizing boron reagents such as silylboranes, cyanoboranes, alkynylboranes, chloroboranes, and aminoboranes are described. They involve transition metal-catalyzed silaboration, cyanoboration, and alkynylboration, which allow efficient synthesis of functionalized organoboron compounds. The application to the catalytic asymmetric silaboration is also demonstrated. Another mode of boron-element addition reaction has been shown by transmetalative carboboration of alkynes, in which the activation of the boron-halogen bonds and the supply of the organic fragment from organometallic reagents are involved as key elementary steps. In addition to those new catalytic reactions for boron-carbon bond formation, we have also utilized amino borane as new iminium ion generators in non-acidic Strecker-type reaction, Mannich reaction, reductive amination, and Ugi reaction. A protective group for the boronyl group in Suzuki-Miyaura cross-coupling was established and used as a temporary mask in iterative synthesis of oligoarenes.
Optically active phosphine ligands possessing stereogenic centers on phosphorus atoms have been synthesized using phosphine-boranes as intermediates. Electron-rich P-chiral phosphine ligands (BisP, MiniPHOS, and DiSquareP) having a bulky alkyl group and a small alkyl group on the phosphorus atom exhibit excellent to almost perfect enantioselectivities in the Rh-catalyzed asymmetric hydrogenation of enamides and related substrates. Air-stable P-chiral phosphine ligands (t-Bu- and 1-Ad-QuinoxP) are also prepared with the phosphine-borane methodology. These ligands have exceedingly high enantioselectivities of up to 99.9% not only in Rh-catalyzed asymmetric hydrogenation but also in Rh- or Pd-catalyzed carbon-carbon bond-forming reactions.
Asymmetric hydrogenation of ketones catalyzed by XylBINAP/chiral diamine-Ru (II), To1BI-NAP/PICA-Ru (II), η6-arene/TsDPEN-Ru (II), and MsDPEN-CpIr (III) complexes affords a variety of sec-ondary alcohols with high enantioselectivity. Complete conversion is attainable with a low catalyst loading. The high catalyst efficiency is rationalized by a novel “metal-ligand cooperative mechanism.”
A catalytic one-step procedure for the chemo- and regioselective acylation of carbohydrates has been developed. With 1 mol% of an organocatalyst, acylation of octyl β-D-glucopyranoside took place preferentially on the secondary hydroxyl group at C (4) among four hydroxyl groups including the primary hydroxyl group at C (6) in 99% selectivity and in 98% yield. Competitive acylation between primary and secondary hydroxyl groups usually takes place chemoselectively at the primary one. On the other hand, with the present catalyst, chemoselective acylation in favor of a secondary hydroxyl group and regioselective acylation in favor of one out of three secondary hydroxyl groups can be performed with perfect selectivity.
Powerful bifunctional organocatalysts, (S)-3-(N-isopropyl-N-3-pyridinylaminomethyl) BINOL (6a) and (S)-3-[2-(diphenylphosphino) phenyl] BINOL (10a), for the aza-Morita-Baylis-Hillman (aza- MBH) reaction, were developed. In these catalysts, chiral Bronsted acid units are connected with a Lewis base unit via a spacer. The acid-base moieties act cooperatively as an enzyme-mimetic catalyst to activate substrates in the carbon-carbon bond forming reaction between a, α, β-unsaturated carbonyl compounds and N-tosylimines with high enantioselectivity.
Two catalytic systems were developed for efficient catalytic enantioselective α-fluorination reactions of carbonyl compounds. Cationic Pd complexes were found to be effective for fluorination of active methine and methylene compounds, and various substrates including β-ketoesters, β-ketophosphonates, and other related compounds were fluorinated in environmentally friendly alcoholic solvents (up to 99% ee). This system was also applicable to the reaction of 3-substituted oxindole derivatives. In addition, we succeeded in developing a novel trinary system NiCl2-binap/R3SiOTf/2, 6-lutidine for the reaction of less acidic α-aryl acetic acid derivatives, and the desired reaction proceeded smoothly to give the corresponding monofluorinated compounds in a highly enantioselective manner (up to 88% ee). Our fluorination reactions are versatile, being applicable to stereoselective synthesis of chiral fluorinated analogues of fundamental building blocks and catalytic asymmetric synthesis of BMS204352, a promising agent for the treatment of stroke.
Palladium-catalyzed alternating copolymerization of olefins with carbon monoxide has been successfully applied to new substrates, namely, 3-perfluoroalkyl-substituted 1-propene (1) and vinyl acetate. The key to success was the choice of ligands. The bulky phosphine-phosphite ligand, (R, S) -BINAPHOS (2e) realized the 1, 2-insertion of 1a, b to enable the subsequent CO insertion. With phosphine-sulfonate ligand 7a, the first example of the alternating copolymerization of vinyl acetate with CO has been performed via CO insertion to the stable chelation intermediate which has never been performed with the conventional ligands for the copolymerization.
Oligoarenes are expected to be useful as frameworks for functional molecules. With the aim of using these molecules as catalyst backbones, we investigated synthetic methods for multifunctionalized oligoarenes. Recently, we developed a repetitive two-step method consisting of a sequence of cross-coupling followed by triflation. Here, our studies on oligoarene synthesis, together with the work of other groups, are described.
This account mainly describes the synthesis and functions of novel artificial double helices recently developed by our group. We have proposed the first design rationale for artificial double helices with a controlled helicity by employing chiral amidinium-carboxylate salt bridges with m-terphenyl ligands, and synthesized several artificial double helices together with triple- and quadruple-stranded helices. An artificial double helix bearing Pt (II) -acetylide complex moieties has proven effective as a catalyst for the asymmetric cyclopropanation, demonstrating that the chiral space provided by double helices can be effective for asymmetric catalytic reactions. Furthermore, we have serendipitously discovered a spiroborate-based double helicate bearing oligophenol strands and water-soluble double helices of oligoresorcinols. The oligoresorcinol double helices bound cyclic and linear oligosaccharides in water to form rotaxanes and hetero-double helices, respectively, with a remarkable selectivity for the glucosidic linkage patterns and chain lengths.