An easy approach to optically active alpha-amino phosphonic acid derivatives by chiral Zn(II)-catalyzed enantioselective amination of phosphonates

A catalytic direct enantioselective electrophilic amination of beta-keto phosphonates has been developed applying chiral bisoxazoline-zinc(II) complexes as the catalyst. The reaction proceeds well for both acyclic and cyclic substrates in high yields and with up to 98% ee using azodicarboxylates as the nitrogen source. The scope of the reaction is, for example, the further transformation to optically active beta-hydroxy-alpha-amino phosphonates with very high stereoselection.     

A stereoselective synthesis of a spiro-bridged bis(α-amino acid) derivative based on Ru(II)-catalysed RCM reactions

Methodology for a stereoselective synthesis of a member of a novel family of spiro-bridged bis(α-amino acid) derivatives is described. The key step in the construction is a spirane annulation reaction effected by a Ru(II)-catalysed ring-closing metathesis (RCM) reaction of an appropriately substituted tetraene. The latter became available after stereocontrolled allylations of 3,3-bis[2-((2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl)ethyl]-1,4-pentadiene, which was prepared in several reaction steps from (2R)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazine as a chiral starting material.     

Cu(II)-catalyzed oscillatory chemical reactions

The role of copper ions in the copper-catalyzed chemical reactions is discussed. It is pointed out that copper ions can induce oscillatory behavior in many systems for the following reasons: (1) Copper cations can exist in three oxidation states (+1, +2 and +3); (2) Copper cations can form precipitates and stable complexes with a large number of reactants and intermediates; (3) Copper ions can participate in both oxidation and reduction processes, due to the surprisingly large range of redox potentials exhibited by the Cu²⁺/Cu⁺ and Cu³⁺/Cu²⁺ couples (known redox potentials span from 0.1 to 1.8 V, depending on the counter-ion or ligand present).     

Copper(II)-catalyzed reactions of activated aromatics

The catalytic reaction of cis-bisglycinato copper(II) monohydrate in the presence of hydrogen peroxide leads to hydroxylation of phenol to give catechol and hydroquinone (1:1.2 ratio) in good yield. 2,6-Dimethylphenol can be hydroxylated by hydrogen peroxide and a catalytic amount of cis-bisglycinato copper(II) monohydrate to give an aggregate of 1,4-dihydroxy-2,6-dimethylbenzene and 2,6-dimethylphenol. A similar reaction of o-cresol gives 2,5-dihydroxytoluene. The reactivity of cis-bisglycinato copper(II) monohydrate in hydrogen peroxide with o-cresol is 4.5 times faster than that of a similar reaction by trans-bisglycinato copper(II) monohydrate. A catalytic reaction of cis-bisglycinato copper(II) monohydrate with aniline in aqueous hydrogen peroxide gives polyanilines in the form of pernigraniline with different amounts of Cu(OH)2 attached to them. The two major components of polyanilines obtained have Mn values of 1040 and 1500, respectively. Resistance of films of these polyanilines increases with temperatures from 40 degrees C to a maximum value at 103 degrees C and then decreases in the region of 103-150 degrees C, showing the property of a thermolectric switch. The aggregate prepared from hydroxylation of 2,6-dimethylphenol shows a similar property in the region of 30-180 degrees C.     

Ni(II) bis(oxazoline)-catalyzed enantioselective syn aldol reactions of N-propionylthiazolidinethiones in the presence of silyl triflates

An enantioselective aldol reaction of N-propionylthiazolidinethione and representative aldehydes is disclosed. The reaction is catalyzed by [Ni(S,S)-t-BuBox](Otf)2. Enolization is effected by 2,6-lutidine, and TMSOTf facilitates catalyst turnover. Syn diastereoselectivities range from 88:12 to 97:3, and enantioselectivities are 90% or greater. Both aromatic and enolizable aliphatic aldehydes are included within the scope of this aldol addition process.     

Radical cascade cyclizations and platinum(II)-catalyzed cycloisomerizations of ynamides

Ynamides are tested as new partners in radical and organometallic transformations. A radical cascade involving a 5-exo-dig cyclization followed by a 6-endo-trig radical trapping transforms ynamides into hetero-polycyclic compounds such as isoindoles, isoindolinones and pyrido-isoindolones. Various ene-tosylynamides react with platinum(II) chloride and lead to bicyclic nitrogenated heterocycles. This unprecedented and easily operated process can be coupled with a hydrolysis of the intermediate cyclic tosylenamides in a one-pot transformation, which provides cyclobutanones.     

Nickel(II)-catalyzed asymmetric alkylation of acyclic oxocarbenium ions with carboxylic acid derivatives

A nickel(II)-catalyzed asymmetric alkylation of acyclic oxocarbenium ions generated in situ from corresponding acetals with carboxylic acid derivatives to prepare β-alkoxyl carbonyl moieties with diverse α-substituents has been disclosed. The method exhibited broad scope of acetals and carboxylic acid derivatives with excellent enantioselectivity and good functional group compatibility, and can be conducted in a gram-scale without obvious loss of efficiency.     

Synthesis and reactions of fluorous carbobenzyloxy (FCbz) derivatives of alpha-amino acids

Fluorous carbobenzyloxy ((F)Cbz) reagents RfCH(2)CH(2)C(6)H(4)CH(2)OC(O)OSu (where Su is succinimidoyl and Rf is C(6)F(13) and C(8)F(17)) have been used to make (F)Cbz derivatives of 18 of the 20 natural amino acids. The potential utility of this new family of reagents in both standard fluorous synthesis with spe separation and fluorous quasiracemic synthesis is illustrated with representative reactions of the (F)Cbz-Phe derivatives.     

NNN pincer Ru(II)-catalyzed dehydrogenative coupling of 2-aminoarylmethanols with nitriles for the construction of quinazolines

An efficient NNN pincer Ru(II)-catalyzed preparation of quinazolines via acceptorless dehydrogenative strategy has been developed. Under the optimized conditions, a broad range of substituted o-aminobenzyl alcohols and (hetero)aryl or alkyl nitriles were well tolerated to afford various 2-substituted quinazolines in high yields. Subsequently, a set of control experiments have been performed to elucidate the reaction mechanism, which underwent alcohol oxidation, nitrile hydration, and cyclocondensation steps. The current protocol is featured with several advantages, such as environmental benignity, operational simplicity, broad substrate scope (compatible with aliphatic nitriles, up to 87% yield), and short reaction time (mostly in 2?h).     

Room-temperature Ru(II)-catalyzed transfer hydrogenation of ketones and aldehydes in air

Transfer hydrogenation (TH) of ketones and aldehydes was efficiently carried out in 2-propanol at room temperature by means of a ruthenium(II) complex catalyst bearing a 2-(benzoimidazol-2-yl)-6-(pyrazol-1-yl)pyridine ligand. TH of the ketone substrates proceeded in air, reaching final TOFs of up to 59,400 h⁻¹, and the reduction of aldehydes proceeded under a nitrogen atmosphere to achieve final TOFs of up to 5940 h⁻¹.     

Ru(II)-catalyzed regioselective C-7 hydroxymethylation of indolines with formaldehyde

A regioselective addition of C7H bonds of indolines to formaldehyde is reported to synthesize a variety of C-7 hydroxymethylated indolines via a Ru(II)-catalyzed CH activation. More importantly, a one-pot CH formylation procedure is also developed to synthesize valuable C7-formyl indoles.     

Ru(II)-catalyzed asymmetric cyclopropanation using chiral diphenylphosphino(oxazolinyl)quinoline ligands

Several chiral 8-diphenylphosphino-2-oxazolinylquinolines were synthesized starting from 2-cyano-8-hydroxyquinoline. These N,N,P-chelates were successfully employed in the Ru(II)-catalyzed asymmetric cyclopropanation reactions of diazo-alkenes. The catalytic system exhibited good reactivity and high thermal stability and provided high yields in the intramolecular cyclopropanation, albeit somewhat decreased enantioselectivities compared to known catalytic systems. A dramatic dependency of the enantioselectivity on the substituents of the oxazoline ring was observed.     

Chiral zinc(II) and copper(II)-catalyzed asymmetric ring-opening reactions of meso-epoxides with aniline and indole derivatives

The ring-opening reactions of meso-epoxides with aniline and indole derivatives proceeded smoothly in water in the presence of Zn(II) and Cu(II) surfactant-type catalysts to afford the corresponding products in moderate to high yields with good to excellent enantioselectivities. Opposite enantiomers were obtained by using Sc(III) and Zn(II) or Cu(II) with the same chiral ligand. Crystal structures of these catalysts may explain the reversal of the enantioselectivity. Some reactions were also tested in dichloromethane (DCM), and it was revealed that the reactions proceeded faster in water than in DCM. Finally, several non-linear effect experiments suggested unique structure of these chiral catalysts.     

trans-Cyclopropyl beta-amino acid derivatives via asymmetric cyclopropanation using a (Salen)Ru(II) catalyst

trans-Cyclopropyl beta-amino acid derivatives can be synthesized in five steps with excellent enantioselectivities using a chiral (Salen)Ru(II) cyclopropanation catalyst in the key asymmetry-induction step. This facile synthesis proceeds with high overall yield and can be used to prepare a number of carbamate-protected (Cbz and Boc are demonstrated) beta-amino acid derivatives.     

Palladium(II)-catalyzed oxidative homo-coupling of 1,3-dimethyluracil derivatives

A palladium-catalyzed oxidative homo-coupling of 1,3-dimethyluracil was examined. Two types of uracil dimer, C5–C5′ linked dimer and C5–C6′ linked dimer were obtained in variable yields depending on the conditions along with a low yield of C5–C5′ and C6–C5′ linked uracil trimer.     

Novel acetoxylation and C-C coupling reactions at unactivated positions in alpha-amino acid derivatives

[Structure: see text] Under special conditions, N-phthaloyl-alpha-amino acid amides of 8-aminoquinoline can be either acetoxylated or arylated selectively at the beta-carbon. In certain cases, arylation can be effected at the gamma-carbon.     

Scope of Ru(II)-catalyzed synthesis of pyridines from alkynes and nitriles

Pyridines can be efficiently synthesized by Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,6-diynes to alpha,omega-dinitriles or electron-deficient nitriles or by Ru(II)-catalyzed [2 + 2 + 2] cocyclization of electron-deficient alkynes and electron-deficient nitriles. The reactions with dinitriles seem likely to proceed via ruthenacyclopentadiene intermediates and the reactions with electron-poor nitriles via azaruthenacyclopentadienes. The reaction with asymmetric electron-deficient alkynes affords 2,3,6-trisubstituted pyridines in good yield.     

Intermolecular rhodium(II)-catalyzed reactions with silicon-substituted carbonyl ylides

[reaction: see text] The Rh(II)-catalyzed reaction of benzyl 2-trialkylsilyl-2-diazoacetates with various acyclic and cyclic ketones affords novel dioxolanones via silicon-substituted carbonyl ylides in up to 98% yield.