Noriyoshi Arai

Asymmetric Hydrogenation of Aromatic, Aliphatic, and α,β-Unsaturated Acyl Silanes Catalyzed by Tol-binap/Pica Ruthenium(II) Complexes : Practical Synthesis of Optically Active α-Hydroxysilanes

Optically active a-hydroxysilanes are regarded as a kind of chiral organometallic compound with a functional group. These molecules and their derivatives have been utilized for stereocontrolled C C bond formation and rearrangement, which resulted in a variety of chiral organic compounds. Asymmetric reduction of acyl silanes is a straightforward method to produce the chiral secondary a-hydroxysilanes. Hydroboration with B-chlorodiisopinocampheylborane (Ipc2BCl) is the most widely used method for this important transformation. The chiral oxazaborolidine reagent is effective for the reaction of acetylenic acyl silanes. 5] A chiral lithium amide reduces a,b-unsaturated acyl silanes with excellent enantioselectivity. However, these procedures require more than one equivalent of the chiral reagent to the substrate. A recently reported transfer hydrogenation catalyzed by an arene/N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (Ts-dpen) Ru complex using 2-propanol as a reducing agent is effective for aromatic acyl silanes. Although this is the only catalytic chemical process for this reaction, the substrateto-catalyst molar ratio (S/C) of 33–200 is not satisfactory for practical use. Asymmetric microbial reductions are reported to exhibit high stereoselectivity merely for specific acyl silane substrates. Thus, the development of an efficient procedure for the catalytic asymmetric reduction of acyl silanes is highly desirable. Hydrogenation possesses advantages over many other reduction methods from the atom-economical and practical points of view. Herein, we disclose for the first time the highly enantioselective hydrogenation of acyl silanes catalyzed by Tolbinap/pica Ru complexes. The reaction is conducted with a S/C value as high as 10000 under 10 atm of H2. A series of benzylic, aliphatic, and allylic a-hydroxysilanes is obtained in up to 99% ee. Benzoyl-tert-butyldimethylsilane (1a ; Scheme 1), prepared by a reported procedure, was selected as a typical substrate for screening the reaction conditions. Hydrogenation of 1a (0.42 g, 0.48m) in ethanol with [RuCl2{(S)-Tol-

Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by the TolBINAP/DMAPEN−Ruthenium(II) Complex: A Significant Effect of N-Substituents of Chiral 1,2-Diamine Ligands on Enantioselectivity

Asymmetric hydrogenation of acetophenone in the presence of Ru(II) catalysts coordinated by TolBINAP and a series of chiral 1,2-diamines was studied. The sense and degree of enantioselectivity were highly dependent on the N-substituents of the diamine ligands. The N-substituent effect was discussed in detail. Among these catalysts, the (S)-TolBINAP/(R)-DMAPEN-Ru(II) complex showed the highest enantioselectivity. The mode of enantioface selection was interpreted by using transition state models based on the X-ray structure of the catalyst precursor. The chiral catalyst effected the hydrogenation of alkyl aryl ketones and arylglyoxal dialkyl acetals to afford the chiral alcohol in >99% ee in the best cases. Hydrogenation of racemic benzoin methyl ether with the chiral catalyst through dynamic kinetic resolution gave the anti-alcohol (syn:anti = 3:97) in 98% ee, while the reaction of alpha-amidopropiophenones resulted in the syn-alcohols (syn:anti = 96:4 to >99:1) in >98% ee.

Asymmetric Hydrogenation of Alkynyl Ketones with the η6-Arene/TsDPEN–Ruthenium(II) Catalyst

Enantioselective hydrogenation of alkynyl ketones catalyzed by Ru(OTf)(TsDPEN)(η(6)-p-cymene) (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) affords the propargylic alcohols in up to 97% ee. The alkynyl moieties are left intact in most cases. The reaction can be conducted with a substrate-to-catalyst molar ratio as high as 5000 under 10 atm of H2. The mode of enantioselection is elucidated with the transition state models directed by the CH/π attractive interaction between the substrate and the catalytic species.

Asymmetric Hydrogenation of Bicyclic Ketones Catalyzed by BINAP/IPHAN−Ru(II) Complex

Hydrogenation of 3-quinuclidinone and bicyclo[2.2.2]octan-2-one with a combined catalyst system of RuCl(2)[(S)-binap][(R)-iphan] and t-C(4)H(9)OK in 2-propanol afforded the chiral alcohols in 97-98% ee. 2-Diphenylmethyl-3-quinuclidinone was hydrogenated with the same catalyst to the cis alcohol with perfect diastereo- and enantioselectivity. The reaction of unsymmetrical ketones with a bicyclo[2.2.1] or -[2.2.2] skeleton gave the corresponding alcohols with high stereoselectivity.

Design of molecular catalysts for achievement of high turnover number in homogeneous hydrogenation

Development of highly active catalysts has been an important research area in synthetic chemistry, especially from a practical point of view. Herein, we focus on the homogeneous catalytic hydrogenation using well-defined molecular catalysts and discuss recent advances in the field with regard to the turnover number for these catalysts.

Asymmetric Hydrogenation of Aromatic Heterocyclic Ketones Catalyzed by the MsDPEN–Cp*Ir(III) Complex

Asymmetric hydrogenation of aromatic heterocyclic ketones catalyzed by Cp*Ir(OTf)(Msdpen) (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the heterocyclic alcohols in 93% to >99% ee. The reaction is conducted in a methanolic solution with a substrate-to-catalyst molar ratio of 200-5000 under 15 atm of H 2 . The heterocyclic rings of substrates are left intact.

A case of anaphylaxis caused by polyethylene glycol analogues

A case of anaphylaxis caused by polyethylene glycol analogues Yoshiko Yamasuji1, Yuko Higashi1, Masanao Sakanoue1, Hiromi Katsue1, Kazuhiro Kawai1, Noriyoshi Arai2 and Takuro Kanekura1 1Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan and 2 Division of Chemical Process Engineering, Hokkaido University, Sapporo, 060-8628, Japan

Stereoselective Preparation of Spiro[4.4] Cyclic Compounds by the Photochemical Activation of Oxazoles

A novel photocyclization of 2-aryloxazole derivatives linked with an alkene moiety through a three-atom spacer at the 5-position gave a range of functionalized spiro[4.4] cyclic compounds that included cyclopentane, tetrahydrofuran, and pyrrolidine moieties in moderate to high yields with excellent diastereoselectivity.

Novel Intramolecular Photocyclization of α-Arylthiophene Derivatives

Photoirradiation of α-arylthiophene derivatives linked with an alkene moiety through a three-atom spacer gave unprecedented cyclobutene-fused perhydrothiapentalene-type compounds in high yields, but neither [2 + 2] nor [4 + 2] cycloaddition products. The reaction afforded a single diastereomer in many cases. The chemical structure and relative configuration of a typical product were unambiguously determined by X-ray crystallographic analysis.

Asymmetric Hydrogenation of Polysubstituted Aromatic Ketones Catalyzed by the DIPSkewphos/PICA Derivative–Ruthenium(II) Complexes

The DIPSkewphos/PICA derivative‐Ru(II) complexes catalyzed asymmetric hydrogenation of significantly sterically hindered 2’,3’,4’,5’,6’‐pentamethylacetophenone, which was not reduced with NaBH4 at 25 °C, with a substrate‐to‐catalyst molar ratio (S/C) of 2000 under 50 atm of H2 in a base‐containing 2‐propanol to afford the alcohol in 99 % ee quantitatively. A series of polysubstituted aromatic ketones was smoothly reacted with an S/C of 300–10,000 under 10–50 atm of H2, yielding the alcoholic products in up to 99 % ee. The catalyst system achieved an industrial‐scale (50 kg) hydrogenation of 2’,6’‐dichloro‐3’‐fluoroacetophenone, affording the alcohol in 96 % isolated yield and in 98 % ee. The obtained alcoholic product is known as a key intermediate for the synthesis of the medicine crizotinib.