Chiral bicyclic NHC/Ir complexes for catalytic asymmetric transfer hydrogenation of ketones.

A diverse series of chiral bicyclic NHC/Ir complexes were prepared via a previously developed divergent synthesis of chiral imidazolium salts. Among the complexes, 8dz was found to be an excellent catalyst precursor for the Ir-catalyzed asymmetric transfer hydrogenation of ketones. The reaction of ketones with 8dz proceeded smoothly to give corresponding alcohols with high enantioselectivities (up to 98%) and productivities (TON up to 4500).

Enantioselective synthesis of planar-chiral ferrocene-fused 4-pyridones and their application in construction of pyridine-based organocatalyst library.

A couple of planar-chiral ferrocene-fused 4-pyridone derivatives 2a and 2b were synthesized in enantiomerically pure form by scalable asymmetric transformations. Pyridones 2 are versatile precursors to various ferrocene-fused pyridine derivatives, which are useful nucleophilic asymmetric organocatalysts.

Synthesis of substituted styrenes and 3-vinylphenols using ruthenium-catalyzed ring-closing enyne metathesis.

The synthesis of substituted styrenes 3 and 3-vinylphenols 9 was achieved by ring-closing enyne metathesis (RCEM)/dehydration of 7 and RCEM/tautomerization of 8, respectively. Those methods provide selective access to unique aromatic compounds and solve the problem of regioisomer formation.

Asymmetric α-amination reaction of alkenyl trifluoroacetates catalyzed by a chiral phosphine-silver complex.

The asymmetric α-amination of alkenyl trifluoroacetates with dialkyl azodicarboxylates catalyzed by the DTBM-SEGPHOS·AgOTf complex takes place in the presence of 2,2,2-trifluoroethanol with almost quantitative yield and high ees of up to 97%.

Catalytic enantioselective Mannich-type reaction via a chiral silver enolate.

A catalytic asymmetric Mannich-type reaction of alkenyl trichloroacetates with aldimines was achieved using SEGPHOS·AgOTf as the chiral precatalyst and N,N-diisopropylethylamine as the base precatalyst in the presence of 2,2,2-trifluoroethanol. Optically active ß-amino ketones with up to >99% ee were syn-selectively obtained in moderate to high yields via the in situ generated chiral silver enolates.

Enantioselective protonation of alkenyl trifluoroacetates catalyzed by chiral tin methoxide.

Go catalytic! A catalytic enantioselective protonation of alkenyl trifluoroacetates was achieved by using an in situ generated chiral tin bromide methoxide as the chiral catalyst in the presence of methanol. Optically active ketones containing a tertiary stereogenic center at the α-position were obtained with enantioselectivities of up to 94 % ee.

Development of asymmetric reactions catalyzed by chiral organotin-alkoxide reagents.

Asymmetric catalysis under almost-neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)-BINOL-derived chiral tin-dibromide reagent that possesses a bulky aryl group at the 3 or 3' position as the chiral pre-catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three-component Mannich-type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N-nitroso aldol reaction of unsaturated lactones with nitrosoarenes.

Synthesis of 4-vinylindoles using ruthenium-catalyzed ring-closing enyne metathesis.

The selective synthesis of substituted 4-vinylindoles by the ring-closing enyne metathesis (RCEM)/dehydration sequence is reported. In contrast with many known methods in which a pyrrole ring is constructed onto a functionalized benzene precursor, this method enables the construction of a benzene ring onto a pyrrole precursor. The RCEM/tautomerization sequence for the synthesis of 7-hydroxy-4-vinylindole is also presented as an application of this method.

Catalytic enantioselective N-nitroso aldol reaction of γ,δ-unsaturated δ-lactones.

A catalytic asymmetric N-nitroso aldol reaction of γ,δ-didehydro-δ-lactones with nitrosoarenes was achieved using chiral tin dibromide as the chiral precatalyst and sodium ethoxide as the base precatalyst in the presence of ethanol. Optically active α-hydroxyamino ketones with up to 99% ee were regioselectively obtained in moderate to high yields from various δ-aryl-substituted γ,δ-didehydro-δ-valerolactones and o-substituted nitrosoarenes.

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.

Voltammetric evaluation on poly α-aspartic acid-zinc ion complex in the helix-coil transition pH region.

Helix-coil transitions of poly α-aspartic acid (PASP) were studied by dc polarography in the presence of Zn(2+) as a marker attached to the polymer. The diffusion current (i(d)) of Zn(2+) declined markedly in the pH range of 3.5-7.4 due to a formation of metal ion-PASP macromolecular complexes. The complex formation also reflects on an increase of the magnitude at ca. 222 nm of CD spectrum, suggesting that PASP forms the helix structure by coordination of Zn(2+) in the corresponding pH region. Helix content, determined by the decrease in i(d) of Zn(2+), corresponds favorably to that by CD measurements. In the lower acidic pH region, the coordination mode of Zn(2+) to PASP is different from that at neutral pH region. The decrease in i(d) of Zn(2+) is independent of the further formation of helix structure. Zn(2+) coordinates with sparsely dissociated carboxylate groups of the helical part of PASP, which bring about an aggregation of polypeptide strands. The diffusion current of the ion attached to the polymer, therefore, is a parameter sensitive to conformational changes of PASP from acidic through neutral pH region.

Construction of carbocyclic ring of indoles using ruthenium-catalyzed ring-closing olefin metathesis.

The selective synthesis of substituted indoles was achieved by the ring-closing olefin metathesis (RCM)/elimination sequence or the RCM/tautomerization sequence of functionalized pyrrole precursors. The RCM/elimination sequence was also applied to double ring closure to yield a substituted carbazole.

Catalytic enantioselective synthesis of chiral γ-butyrolactones.

A tandem catalytic asymmetric aldol reaction/cyclization of ß,γ-didehydro-γ-lactones with aldehydes was achieved using chiral tin dibromide as a chiral precatalyst and sodium alkoxide as a base precatalyst. Optically active trans-ß,γ-disubstituted γ-butyrolactones were selectively obtained in moderate to high yields with up to 99% ee from γ-aryl-substituted ß,γ-didehydro-γ-butyrolactones and bulky aliphatic aldehydes.

Synthesis of biaryl compounds using tandem ruthenium-catalyzed ring-closing metathesis.

Tandem ring-closing enyne metathesis (RCEM)/ring-closing olefin metathesis (RCM) of tetraenynes with Grubbs second-generation catalyst, followed by elimination, was found to be a new and efficient synthetic approach to biaryl compounds. A preliminary asymmetric version of this approach, which used homochiral Ru-alkylidene catalysts, is also presented.

Enantiopure 1,2-bis(tert-butylmethylphosphino)benzene as a highly efficient ligand in rhodium-catalyzed asymmetric hydrogenation.

An electron-rich P-stereogenic bisphosphine ligand named "BenzP*" was conveniently prepared from o-dibromobenzene and enantiopure tert-butylmethylphosphine-borane. Its rhodium complex exhibited excellent enantioselectivities of up to 99.9% and high catalytic activity of up to 10,000 h(-1) TOF in asymmetric hydrogenations of various functionalized alkenes.

Bicyclic imidazoles for modular synthesis of chiral imidazolium salts.

The preparation of new chiral bicyclic imidazoles 5 and their transformation into imidazolium salts 6 and 7 are reported. The utility of the salts as precursors for chiral N-heterocyclic carbenes was demonstrated by the synthesis of C-N-C pincer Ni-complex 13h, the structure of which was characterized by single-crystal X-ray analysis.

Enantioselective nitroso aldol reaction catalyzed by QuinoxP*.silver(I) complex and tin methoxide.

A catalytic enantioselective O-nitroso aldol reaction of alkenyl trichloroacetates with nitrosoarenes was achieved using the (R,R)-t-Bu-QuinoxP*.AgOAc complex as the chiral catalyst and Bu(2)Sn(OMe)(2) as the achiral cocatalyst in the presence of methanol. Optically active alpha-aminooxy ketones with up to 99% ee were regioselectively obtained in high yields from various alkenyl trichloroacetates of cyclic ketones.

Haemodynamic changes in the fingers after free radial forearm flap transfer: a prospective study using SPP.

Harvesting the radial forearm flap may cause circulatory problems in the donor arm. To investigate the influence on donor hands after radial forearm flap harvesting, we assessed the process of circulatory changes prospectively by measuring skin perfusion pressure (SPP) that is clinically useful in detecting vascular lesions. The records of 17 patients (14 men and 3 women aged 59.7+/-11.8 years) who had undergone free radial forearm flap transfer for head and neck reconstruction, between December 2005 and April 2007, were analysed. SPP in the thumb (finger I), the middle finger (III) and the little finger (V) was measured in the 17 patients preoperatively and 1 month and 3, 6, 9 and 12 months postoperatively. All statistical tests were two sided, with a significance level defined as p<0.05. Preoperatively, baseline SPP was more dominant in finger I than in finger V. Postoperatively, SPP changed significantly in both fingers, while it showed no change in finger III and tended to be higher in finger I than in the other two. Harvesting the free radial forearm flap reduces skin perfusion in the fingers of the donor arm and, we assume, leads to a re-distribution of blood flow to the fingers, with the residual ulnar artery still supplying more blood flow to finger I than to finger V. This suggests the presence of an autoregulating mechanism whereby blood perfusion to the fingers is controlled by the physiological demands of individual fingers.

Catalytic asymmetric three-component Mannich-type reaction of alkenyl trichloroacetates.

A catalytic enantioselective three-component Mannich-type reaction of alkenyl trichloroacetates, ethyl glyoxalate, and aniline derivatives was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-trifluoromethylphenyl group at the 3- and 3'-positions as the chiral precatalyst in the presence of sodium ethoxide, sodium iodide, and ethanol. Optically active beta-amino ketones with up to 98% ee were syn-selectively obtained in high yields even from imines possessing a polar amino group under the influence of the in situ generated chiral tin bromide ethoxide.