Asymmetric Cyanation of α-Ketimino Ester Derivatives with Chiral Ru-Li Combined Catalysts.

Asymmetric cyanation of α-ketimino esters catalyzed by combined systems of amino acid/BINAP derivative/Ru(II) complexes and lithium compounds was examined. The use of an appropriate combination of amino acid and BINAP ligands achieved high enantioselectivity for a variety of α-alkynyl (Val/XylBINAP/Ru), α-alkenyl (Val/TolBINAP/Ru), and α-aryl imino esters (Val/XylBINAP/Ru) as well as an isatin-derived cyclic imino amide (t-Leu/BINAP/Ru) to afford the α-cyano-α-amino esters and the amide with an α-nitrogen-substituted quaternary chiral center with up to 98% ee.

Asymmetric Hydrogenation of α-Alkyl-Substituted ß-Keto Esters and Amides through Dynamic Kinetic Resolution.

Asymmetric hydrogenation of α-alkyl-substituted ß-keto esters and amides with the DIPSkewphos/3-AMIQ-Ru(II) catalyst system through dynamic kinetic resolution was examined. A series of ß-keto esters and amides with a simple or functionalized α-alkyl group were applicable to this reaction, affording the α-substituted ß-hydroxy esters and amides in ≥99% ee (anti/syn ≥ 99:1) in many cases. The 5 g scale reaction was readily achieved. The mode of enantio- and diastereoselection in the transition state model was proposed.

Ag-Catalyzed Cyanomethylation of Amines Using Nitromethane as a C1 Source.

A new methodology to afford α-amino nitriles through oxidative cyanomethylation of amines using nitromethane as the methylene source in the presence of Me3SiCN without the addition of an external oxidant was developed. A catalytic amount of AgCN and a stoichiometric amount of LiBF4 cooperatively promoted the transformation. A wide variety of the amines, including both aromatic compounds and aliphatic ones, which are labile under oxidative conditions, were applicable to the reaction.

Asymmetric Hydrogenation of α-Amino Esters into Optically Active ß-Amino Alcohols through Dynamic Kinetic Resolution Catalyzed by Ruthenabicyclic Complexes.

Racemic α-substituted α-amino esters were hydrogenated into enantioenriched ß-amino alcohols through dynamic kinetic resolution with chiral ruthenabicyclic complexes. The reaction was carried out with a substrate/catalyst molar ratio of 200-1000 under 15 atm of H2 at 25 °C to afford a variety of ß-substituted ß-aminoethanols in up to 96% ee (24 examples). The mechanistic studies including deuteration experiments suggested that the reaction proceeds with 1,2-hydride migration of the α-amino acetalate intermediate into the α-hydroxy imine followed by the continuous reduction of the imino compound, affording the amino alcohol product.

Aerobic Allylic Amination Catalyzed by a Pd(OAc)2/P(OPh)3 System with Low Catalyst Loading.

A Pd(OAc)2/P(OPh)3 combination catalyzed Tsuji-Trost-type allylic amination under aerobic conditions. Both aromatic and aliphatic secondary amines were transformed into the corresponding allylic amines with a tiny amount of the catalyst system (typically 0.02 mol % Pd), only when allylic phosphates were employed as electrophiles. Other typical electrophiles, such as allylic acetate and carbonate, were marginally reactive. A Pd(0) complex, Pd[P(OPh)3]3, formed in situ was suggested as an active species by mechanistic experiments.

Photosensitized Intramolecular [2+2] Cycloaddition of 1H-Pyrrolo[2,3-b]pyridines Enabled by the Assistance of Lewis Acids.

The [2+2] photocycloaddition of alkenyl-tethered 1H-pyrrolo[2,3-b]pyridine derivatives sensitized with 3',4'-dimethoxyacetophenone under irradiation by a high-pressure mercury lamp through Pyrex glass was dramatically accelerated by the addition of Lewis acids, preferably Mg(OTf)2, to give the products stereoselectively in high yields. The reaction without a Lewis acid gave only small amounts of the [2+2] cycloaddition products. Conformational fixation of the substrates by coordination with a Lewis acid was presumed to facilitate the cycloaddition.

Nucleophilic Isocyanation.

Isonitriles are frequently employed as both substrates for organic transformations and ligands for organometallic chemistry. However, despite the wide application of the isonitriles, their synthesis generally depends on the traditional dehydration of N-formamide. "Nucleophilic isocyanation" using cyanide as an N-nucleophile is another straightforward strategy affording the corresponding isonitriles. This method has been available since the 19th century but is still an immature procedure and is therefore more rarely used. In this review, we summarize the concepts and recent progress in nucleophilic isocyanation, including the relatively rare examples of catalytic isocyanation.

Stereoselective Construction of Methylenecyclobutane-Fused Indolines through Photosensitized [2+2] Cycloaddition of Allene-Tethered Indole Derivatives.

Irradiation of 1-(hexa-4,5-dienoyl)indole derivatives in the presence of an aromatic ketone by a high-pressure mercury lamp through Pyrex glass gave the corresponding cyclized products stereoselectively in high yields. The major part of the products was an all- cis-fused methylenecyclobutane-type compound produced through [2+2] cycloaddition, accompanied by small amounts of alkynes via 1,5-hydrogen transfer of a biradical intermediate. Among a range of aromatic ketones, 3',4'-dimethoxyacetophenone was found to sensitize the substrate quite effectively.

Chemoselectivity Control in the Asymmetric Hydrogenation of γ- and δ-Keto Esters into Hydroxy Esters or Diols.

The asymmetric hydrogenation of aromatic γ- and δ-keto esters into optically active hydroxy esters or diols under the catalysis of a novel DIPSkewphos/3-AMIQ-RuII complex was studied. Under the optimized conditions (8 atm H2 , Ru complex/t-C4 H9 OK=1:3.5, 25 °C) the γ- and δ-hydroxy esters (including γ-lactones) were obtained quantitatively with 97-99 % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H2 , [t-C4 H9 OK]=50 mm, 40 °C), the 1,4- and 1,5-diols were obtained predominantly with 95-99 % ee. The reactivity of the ester group was notably dependent on the length of the carbon spacer between the two carbonyl moieties of the substrate. The reaction of ß- and ϵ-keto esters selectively afforded the hydroxy esters regardless of the reaction conditions. This catalyst system was applied to the enantioselective and regioselective (for one of the two ester groups) hydrogenation of a γ-ϵ-diketo diester into a trihydroxy ester.

Photochemically Promoted Aza-Diels-Alder-Type Reaction: High Catalytic Activity of the Cr(III)/Bipyridine Complex Enhanced by Visible Light Irradiation.

Aza-Diels-Alder-type cycloaddition reactions between a range of N-arylimines and functionalized alkenes were effectively catalyzed by the Cr(III)/bipyridine complex under irradiation of blue light, to give the corresponding 1,2,3,4-tetrahydroquinoline derivatives in high yields with excellent diastereoselectivity. Typically, the reaction of benzylideneaniline with 1-vinyl-2-pyrrolidinone proceeded smoothly with a substrate-to-catalyst molar ratio (S/C) of 1000 and completed within 4 h at room temperature (20-25 °C), affording the cycloaddition product in 97% yield.

Double Asymmetric Hydrogenation of Linear ß,ß-Disubstituted α,ß-Unsaturated Ketones into γ-Substituted Secondary Alcohols using a Dual Catalytic System.

Double asymmetric hydrogenation of linear ß,ß-disubstituted α,ß-unsaturated ketones catalyzed by the DM-SEGPHOS/DMAPEN/RuII complex with t-C4 H9 OK afforded the γ-substituted secondary alcohols in high diastereo- and enantioselectivities. Some mechanistic experiments suggested that two different reactive species, type (I) and (II), were reversibly formed in this catalytic system: Type (I) with the diamine ligand DMAPEN enantioselectively hydrogenated the enones into the chiral allylic alcohols, and type (II) without the diamine ligand diastereoselectively hydrogenated the allylic alcohols into the γ-substituted secondary alcohols. This dual catalysis protocol was successfully applied to the reaction of a variety of aliphatic- and aromatic-substituted enone substrates.

Advancement in Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric Isomerization of Allylic Alcohols.

Catalytic asymmetric hydrogenation of ketones through the "metal-ligand cooperative mechanism" has been improved in terms of the efficiency, stereoselectivity, and scope of substrates by varying the arrangement of the catalyst structure and reaction conditions. Imino compounds are also smoothly converted to the optically active amines with appropriate catalysts. This type of catalyst exhibits excellent performance on the asymmetric isomerization of primary allylic alcohols into the optically active aldehydes. This personal account describes recent progress on these topics.

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.

Asymmetric conjugate hydrocyanation of α,ß-unsaturated N-acylpyrroles with the Ru(phgly)2(binap)-CH3OLi catalyst system.

Asymmetric conjugate hydrocyanation of α,ß-unsaturated carboxylic acid derivatives catalyzed by a Ru[(S)-phgly]2[(S)-binap]-CH3OLi system was examined. The N-acylpyrrole gave the best result in terms of reactivity and enantioselectivity. A series of substrates with alkyl or heterosubstituted alkyl groups at the ß-position reacted with a substrate-to-catalyst molar ratio of 200-2000 to afford the ß-cyano products in the range of 88%->99% ee. The mode of enantioselection in the hydrocyanation was proposed.

Enantioselective isomerization of primary allylic alcohols into chiral aldehydes with the tol-binap/dbapen/ruthenium(II) catalyst.

Efficient isomerization: The title reaction was catalyzed by the [RuCl2{(S)-tol-binap}{(R)-dbapen}]/KOH system in ethanol at 25 °C (see scheme). A series of E- and Z-configured aromatic and aliphatic allylic alcohols, including a simple primary alkyl-substituted compound (E)-3-methyl-2-hepten-1-ol, were transformed into the chiral aldehydes with at least 99 % ee. dbapen = 2-dibutylamino-1-phenylethylamine, tol-binap = 2,2'-bis(di-4-tolylphosphanyl)-1,1'-binaphthyl.

Asymmetric hydrogenation of alkynyl ketones with the η(6)-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.

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.