Tsuneo Imamoto

Organocerium reagents. Nucleophilic addition to easily enolizable ketones

Abstract Organocerium reagents, prepared from organolithiums and anhydrous cerium (III) chloride, react cleanly with easily enolizable ketones to afford the addition products in good to excellent yields.

Rigid P-Chiral Phosphine Ligands with tert-Butylmethylphosphino Groups for Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized Alkenes

Both enantiomers of 2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*), 1,2-bis(tert-butylmethylphosphino)benzene (BenzP*), and 1,2-bis(tert-butylmethylphosphino)-4,5-(methylenedioxy)benzene (DioxyBenzP*) were prepared in short steps from enantiopure (S)- and (R)-tert-butylmethylphosphine-boranes as the key intermediates. All of these ligands were crystalline solids and were not readily oxidized on exposure to air. Their rhodium complexes exhibited excellent enantioselectivities and high catalytic activities in the asymmetric hydrogenation of functionalized alkenes, such as dehydroamino acid derivatives and enamides. The practical utility of these catalysts was demonstrated by the efficient preparation of several chiral pharmaceutical ingredients having an amino acid or a secondary amine component. A rhodium complex of the structurally simple ligand BenzP* was used for the mechanistic study of asymmetric hydrogenation. Low-temperature NMR studies together with DFT calculations using methyl α-acetamidocinnamate as the standard model substrate revealed new aspects of the reaction pathways and the enantioselection mechanism.

Cerium chloride-promoted nucleophilic addition of grignard reagents to ketones an efficient method for the synthesis of tertiary alcohols

Abstract In the presence of anhydrous cerium(III) chloride, Grignard reagents react with Ketones to afford addition products in high yields, even though the substrates are susceptible to abnormal reactions with Grignard reagents alone.

Asymmetric Hydrogenation Catalyzed by (S,S)-R-BisP*-Rh and (R,R)-R-MiniPHOS Complexes: Scope, Limitations, and Mechanism

A new class of chiral C2-symmetric bis(trialkyl)phosphine ligands has been prepared and used in Rh(I)-catalyzed asymmetric hydrogenation reactions. The ligands, 1,2-bis(alkylmethylphosphino)ethanes 1a-g(abbreviated as BisP*, alkyl = t-butyl, 1-adamantyl, 1-methylcyclohexyl, 1,1-diethylpropyl, cyclopentyl, cyclohexyl, isopropyl) and 1,2-bis(alkylmethylphosphino)methanes 2a-d(abbreviated as MiniPHOS, alkyl = t-butyl, cyclohexyl, isopropyl, phenyl) are prepared by a simple synthetic approach based on the air-stable phosphine–boranes. These new ligands give the corresponding Rh(I) complexes, which are effective catalytic precursors for the asymmetric hydrogenation of a representative series of dehydroamino acids and itaconic acid derivatives. Enantioselectivities observed in these hydrogenations are universally high and in many cases exceed 99%. X-Ray characterization of four precatalysts, study of the pressure effects, deuteration experiments, and characterization of the wide series of intermediates in the catalytic cycle are used for the discussion of the possible correlation between the structure of the catalysts and the outcome of the catalytic asymmetric hydrogenation.

Carbonyl addition reactions promoted by cerium reagents

Organocerium reagents are generated by the reaction of organolithiums with anhydrous cerium chloride or cerium io- dide. The reagents are less basic than organolithiums or Gri- gnard reagents, and they react with various carbonyl compounds to give the corresponding addition products in high yields, even though the substrates are susceptible to enolization or metal-halogen exchange with simple organolithiums. The same reagents react with d,g-unsaturated carbonyl compounds to yield lr2-addition products with high regioselectivity. It has also been found that cerium chloride significantly pro- motes the addition reactions of Grignard reagents to carbonyl compounds with remarkable suppression of abnormal reactions. Various tertiary alcohols, which are difficult to prepare by the conventional Grignard reaction, can be synthesized by this method. Several applications of this methodology to practical organic syntheses are described.

Chemoselective transfer hydrogenation of α,β-unsaturated ketones catalyzed by pincer-Pd complexes using alcohol as a hydrogen source.

A pincer-Pd complex was utilized in the chemoselective transfer hydrogenation of α,β-unsaturated ketones using n-BuOH as a hydrogen source and solvent. Good to excellent yields were obtained for various substrates even with reducible groups. Based on deuterium-labeling experiments, the reaction mechanism is proposed to occur via a pincer-Pd-hydride intermediate.

Unsymmetrical P-Chirogenic Bis(phosphane) Ligands: Their Preparation and Use in Rhodium-Catalyzed Asymmetric Hydrogenation

A series of bis(phosphanes) (SP,SP′)-R1(Me)PCH2CH2P′R2R3 (1a−k; R1, R2, and R3 = 1-adamantyl, tert-butyl, cyclohexyl, cyclopentyl, isopropyl, methyl, phenyl; abbreviated as unsymmetrical BisP*) has successfully been synthesized, by coupling of the (RP)-configured tosylates 5a−d or mesylates 6a−g with lithiated (SP)-R1(Me)PH−BH3 adducts. Asymmetric hydrogenations catalyzed by rhodium complexes of the unsymmetrical BisP* moieties as ligands revealed extremely high enantioselectivities − 99% (9b) and 98% (9e) − when the trisubstituted and tetrasubstituted dehydro-α-amino acid derivatives 8b and 8e, respectively, were used as substrates. It was found that unsymmetrical BisP* species tended to exhibit higher enantioselectivity than C2-symmetrical BisP* species in the Rh-catalyzed hydrogenation of (Z)-dehydro-β-amino acid and enamide derivatives. These results implied that the differentiation between the chiral environments at the two phosphorus atoms could effectively achieve higher enantioselectivity. For each substrate, moreover, it was possible to improve the enantioselectivity by changing the combination of substituents on the two phosphorus atoms. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Reductive coupling of carbonyl compounds to pinacols by using low-valent cerium

Abstract Aldehydes and ketones, on treatment with a low-valent cerium reagent, undergo reductive dimerization to produce the corresponding pinacols in high yield.

The reaction of carbonyl compounds with diiodomethane in the presence of samarium: novel syntheses of iodohydrins and cyclopropanols

Abstract The iodomethylation of carbonyl compounds giving iodohydrins has been achieved under ordinary conditions by the use of diiodomethane and samarium. A novel synthesis of cyclopropanols from α-haloketones or 1,2-dibenzoylethane is also described.

Phosphine catalyzed aldol reaction between ketene silyl acetals and aldehydes: nucleophilic O–Si and C–Si bond cleavage by phosphines

Abstract A highly nucleophilic phosphine, tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP), catalyzes the aldol reaction between ketene silyl acetals and aldehydes to give the corresponding aldol products in good to high yields. This reaction is considered to proceed through naked enolates produced by nucleophilic O–Si and C–Si bond cleavage.