Highly enantioselective hetero Diels–Alder reactions of N-sulfinyl dienophiles promoted by copper(II)- and zinc(II)-chiral bis(oxazoline) complexes

Hetero Diels–Alder reactions of 1,3-cyclohexadiene with N-sulfinyl dienophiles 1a or 1b, promoted by Cu(II)- or Zn(II)-chiral bis(oxazoline) complexes, afforded endo adducts in high yields (up to 85%) and enantiomeric excess (e.e. of up to >98%) under stoichiometric conditions. With 10 mol% loading of the Zn(II) catalyst up to 75% e.e. was obtained for the endo adduct (endo:exo=10:1, total yield 68%).     

Oxidation of alcohols with hydrogen peroxide catalyzed by soluble iron and osmium derivatives

Summary Osmium chloride OsCl₃ efficiently catalyzes (yields of products up to 90%, turnover numbers (TON) up to 1500) the oxidation of 2-cyanoethanol with hydrogen peroxide to produce the corresponding aldehyde and acid. Oxidation of isopropanol over OsCl₃ gave acetone in 58% yield. The reactions were carried out either in acetonitrile or without any solvent. The analogous iron compound FeCl₃ was found to be less efficient in the oxidation of 2-cyanoethanol (yields of products up to 67%, TON up to 135). Oxidation of isopropanol in this case gave acetone (yield 53%) and acetic acid (yield 11%). Some other soluble derivatives of iron or osmium exhibited noticeably lower catalytic activity in the alcohol oxidation with H₂O₂.     

Chiral squaramides catalyzed diastereo- and enantioselective Michael addition of α-substituted isocyanoacetates to N-aryl maleimides

An efficient diastereo- and enantioselective Michael addition of α-substituted isocyanoacetates to N-aryl maleimides catalyzed by quinine or cyclohexane-1,2-diamine derived squaramide catalysts has been disclosed, affording the corresponding adducts in good yields (up to 99%), high diastereoselectivities (up to >20:1 dr) and good to excellent enantioselectivities (up to 94% ee) under mild conditions.     

Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/linked-BINOL complex: synthesis of either anti- or syn-beta-amino alcohols

Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.     

Enantioselective water-soluble iron–porphyrin-catalyzed epoxidation with aqueous hydrogen peroxide and hydroxylation with iodobenzene diacetate

The asymmetric epoxidation of styrene derivatives by H₂O₂ (or UHP) to give optically active epoxides (ee up to 81%) and hydroxylation of alkanes to give optically active secondary alcohols (ee up to 78%) were carried out in methanol and water using chiral water-soluble iron porphyrins as catalysts.     

Furfuryl vinyl ethers in [4+2]-cycloaddition reactions

For the first time [4+2]-cycloaddition reactions were carried out between furfuryl vinyl ethers and typical dienophiles and heterodienes proceeding in uncatalyzed conditions and resulting in previously unknown heterocyclic systems containing either free vinyloxy groups or furfuryl substituents. With maleic anhydride and maleimide furfuryl vinyl ethers afforded 1-(vinyloxyalkyl)tricyclodec-8-ene-3,5-diones in up to 72% yields, and with N-benzylideneaniline or acrolein the corresponding functionally substituted tetrahydroquinolines (yield up to 65%) or 3,4-dihydropyrans (yield 23–50%) were obtained.     

Stereo‐ and Chemodivergent NHC‐Promoted Functionalisation of Arylalkylketenes with Chloral

Stereo‐ and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N‐heterocyclic carbenes, giving selectively either β‐lactones (up to 88:12 dr, up to 94 % ee) or α‐chloroesters (up to 94 % ee). Either 2‐arylsubstitution or an α‐branched iPr alkyl substituent within the ketene favours the chlorination pathway, allowing chloral to be used as an electrophilic chlorinating reagent in asymmetric catalysis.     

Modular ligands in asymmetric synthesis. Copper-mediated cyclopropanation

The chiral imidazoline/copper catalyst system efficiently mediates asymmetric intermolecular cyclopropanations. Complexes derived from (R,R)- or (S,S)-1,1-diphenylethylenediamine, cyclic ketones, and Cu(I) or Cu(II) triflates were compared. The reaction between (−)-menthyl diazoacetate and 1,1-diphenylethylene affords cyclopropane carboxylates in up to 80% yield and with up to 78% de.     

Effect of medium acidity on the efficiency of oxidation of 2,4,6-trinitrotoluene to 2,4,6-trinitrobenzoic acid

An effect of boric acid additives on oxidation of 2,4,6-trinitrotoluene (TNT) to 2,4,6-trinitrobenzoic acid (TNBA) with chromic anhydride in concentrated (96—100%) H₂SO₄ has been studied. In the presence of tetrahydrosulfatoboric acid HB(HSO₄)₄ formed in situ (up to 5 mol.%) or added as a preliminary prepared solution (up to 1 mol. %), TNT is selectively oxidized to TNBA in the yields up to 95—99%. The mechanism including formation of TNT dication as a key step of its oxidation at the methyl group has been suggested.     

Asymmetric reductive amination of boron-containing aryl-ketones using ω-transaminases

The asymmetric reductive amination of aryl-ketones bearing various boron-functionalities (acid, ester or potassium trifluoroborates) was investigated employing enantiocomplementary ω-transaminases as catalysts. Under the optimized conditions, high conversions (up to 94%) and excellent ee’s (up to >99%) were obtained providing access to both (R)- and (S)-configured amino-aryl boronates under mild reaction conditions.     

New P,N-ferrocenyl ligands for rhodium-catalyzed hydroboration and palladium-catalyzed allylic alkylation

A set of nine new chiral P,N-ferrocenyl ligands for metal-catalyzed enantioselective reactions has been prepared. The rhodium-catalyzed hydroboration of styrene with catechol borane proceeded with high regioselectivity (up to 97:3) or with high enantioselectivity (up to 92% ee) depending on the catalyst. Good results were also obtained in the palladium-catalyzed asymmetric alkylation of 1,3-diphenylallylic systems (up to 94% ee).     

Chiral Diamine-catalyzed Asymmetric Aldol Reaction

A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine (1R,2R)-cyclohexane-1,2-diamine(6) and trifluoroacetic acid (TFA) was employed for asymmetric Aldol reaction in em-PrOH at room temperature. A loading of 10%(molar fraction) catalyst 6 with TFA as a cocatalyst could catalyze the Aldol reactions of various ketones or aldehydes with a series of aromatic aldehydes, furnishing Aldol pro- ducts in moderate to high yields(up to >99%) with enantioselectivities of up to >99% and diastereoselectivities of up to 99:1.     

Calixarene-based chiral primary amine thiourea promoted highly enantioselective asymmetric Michael reactions of α,α-disubstituted aldehydes with maleimides

Calix[4]arene based chiral bifunctional thiourea-primary amines have been shown to act as effective catalysts for the Michael addition of aldehydes to maleimides for the first time. The corresponding adducts were generally obtained preferentially in (R)- or (S)-forms with high yields (up to 99%) and with high to excellent enantioselectivities (up to 98% ee).     

Triggering Activity of Catalytic Rod‐Like Supramolecular Polymers

Supramolecular polymers based on benzene‐1,3,5‐tricarboxamides (BTAs) functionalized with an L ‐ or D ‐proline moiety display high catalytic activity towards aldol reactions in water. High turnover frequencies (TOF) of up to 27×10^?4 s^?1 and excellent stereoselectivities (up to 96 % de, up to 99 % ee) were observed. In addition, the catalyst could be reused and remained active at catalyst loadings and substrate concentrations as low as 0.1 mol % and 50 mM , respectively. A temperature‐induced conformational change in the supramolecular polymer triggers the high activity of the catalyst. The supramolecular polymer’s helical sense in combination with the configuration of the proline (L ‐ or D ‐) is responsible for the observed selectivity.     

Electrophilic addition of alcohols to 1-vinyl-2-phenylazopyrroles and unexpected formation of 2-methylquinoline

1-Vinyl-2-phenylazopyrroles react with alcohols in the presence of acids or PdCl₂ to give 1-(1-alkoxyethyl)-2-phenylazopyrroles in up to 49% yield. In the presence of trifluoroacetic acid 2-methylquinoline unexpectedly formed (yield up to 26%) involving into the reaction the phenylazo and 1-vinyl groups.     

Organocatalysis of asymmetric aldol reaction in water: comparison of catalytic properties of (S)-valine and (S)-proline amides

(S)-Valine amides containing (S)- or (R)-α-phenylethyl substituents at N¹ atom efficiently catalyze asymmetric aldol reactions between cyclic (heterocyclic) ketones and aromatic aldehydes in water, predominantly giving rise to the aldol anti-diastereomers in high yields (up to 98%) and enantiomeric excess (up to 94%).     

Biocatalytic direct asymmetric aldol reaction using proteinase from Aspergillus melleus

The direct asymmetric aldol reaction of aromatic aldehydes with cyclic or acyclic ketones was catalyzed by proteinase from Aspergillus melleus (AMP) in acetonitrile in the presence of water. A wide range of substrates could be transformed into the corresponding aldol products in yields up to 89%, enantioselectivities up to 91% ee and diastereoselectivities up to >99:1 (anti/syn). This work provided an example of enzyme catalytic promiscuity that widens the applicability of this biocatalyst in organic synthesis without the need for additional cofactors or special equipment.     

(S)-Threonine/α,α-(S)-diphenylvalinol-derived chiral ionic liquid: an immobilized organocatalyst for asymmetric syn-aldol reactions

Chiral ionic liquids containing (S)- or (R)-threonine amide and α,α-(S)-diphenylvalinol units were synthesized In the presence of the (S)-threonine-derived catalyst reactions between ketones with secondary carbon atom(s) at the α-position with respect to the carbonyl group and aromatic (heteroaromatic) aldehydes afforded the corresponding syn-aldols in high yields (up to 99%) and with high diastereo-(syn/anti up to 97:3) and enantioselectivity (up to 99% ee), which was maintained over three reaction cycles.     

Mechanochemical Synthesis of Short DNA Fragments

We demonstrate the first mechanochemical synthesis of DNA fragments by ball milling, enabling the synthesis of oligomers of controllable sequence and length using multi-step, one-pot reactions, without bulk solvent or the need to isolate intermediates. Mechanochemistry allowed for coupling of phosphoramidite monomers to the 5′-hydroxyl group of nucleosides, iodine/water oxidation of the resulting phosphite triester linkage, and removal of the 5′-dimethoxytrityl (DMTr) protecting group in situ in good yields (up to 60 % over three steps) to produce DNA dimers in a one-pot manner. H-Phosphonate chemistry under milling conditions enabled coupling and protection of the H-phosphonate linkage, as well as removal of the 5′-DMTr protecting group in situ, enabling a one-pot process with good yields (up to 65 % over three steps, or ca. 87 % per step). Sulfurization of the internucleotide linkage was possible using elemental sulfur (S8) or sulfur transfer reagents, yielding the target DNA phosphorothioate dimers in good yield (up to 80 % over two steps). This work opens the door to creation of solvent-free synthesis methodologies for DNA and RNA therapeutics.     

Cu(I)-catalyzed asymmetric oxidative cross-coupling of 2-naphthol derivatives

The asymmetric oxidative coupling reaction between 2-naphthol or binaphthol derivatives and 3-hydroxy-2-naphthoate derivatives with the copper(I)-(S)-(−)-isopropylidenebis(4-phenyl-2-oxazoline) catalyst was carried out. The reaction proceeded in a highly cross-coupling selective manner (≤99.7%) to produce the binaphthyl or quaternaphthyl derivative in good yield (≤92%) with enantioselectivity of up to 74%.