Efficient Cluster‐Based Catalysts for Asymmetric Hydrogenation of α‐Unsaturated Carboxylic Acids

The new clusters [H₄Ru₄(CO)₁₀(μ‐1,2‐P‐P)], [H₄Ru₄(CO)₁₀(1,1‐P‐P)] and [H₄Ru₄(CO)₁₁(P‐P)] (P‐P=chiral diphosphine of the ferrocene‐based Josiphos or Walphos ligand families) have been synthesised and characterised. The crystal and molecular structures of eleven clusters reveal that the coordination modes of the diphosphine in the [H₄Ru₄(CO)₁₀(μ‐1,2‐P‐P)] clusters are different for the Josiphos and the Walphos ligands. The Josiphos ligands bridge a metal–metal bond of the ruthenium tetrahedron in the “conventional” manner, that is, with both phosphine moieties coordinated in equatorial positions relative to a triangular face of the tetrahedron, whereas the phosphine moieties of the Walphos ligands coordinate in one axial and one equatorial position. The differences in the ligand size and the coordination mode between the two types of ligands appear to be reflected in a relative propensity for isomerisation; in solution, the [H₄Ru₄(CO)₁₀(1,1‐Walphos)] clusters isomerise to the corresponding [H₄Ru₄(CO)₁₀(μ‐1,2‐Walphos)] clusters, whereas the Josiphos‐containing clusters show no tendency to isomerisation in solution. The clusters have been tested as catalysts for asymmetric hydrogenation of four prochiral α‐unsaturated carboxylic acids and the prochiral methyl ester (E)‐methyl 2‐methylbut‐2‐enoate. High conversion rates (>94 %) and selectivities of product formation were observed for almost all catalysts/catalyst precursors. The observed enantioselectivities were low or nonexistent for the Josiphos‐containing clusters and catalyst (cluster) recovery was low, suggesting that cluster fragmentation takes place. On the other hand, excellent conversion rates (99–100 %), product selectivities (99–100 % in most cases) and good enantioselectivities, reaching 90 % enantiomeric excess (ee) in certain cases, were observed for the Walphos‐containing clusters, and the clusters could be recovered in good yield after completed catalysis. Results from high‐pressure NMR and IR studies, catalyst poisoning tests and comparison of catalytic properties of two [H₄Ru₄(CO)₁₀(μ‐1,2‐P‐P)] clusters (P‐P=Walphos ligands) with the analogous mononuclear catalysts [Ru(P‐P)(carboxylato)₂] suggest that these clusters may be the active catalytic species, or direct precursors of an active catalytic cluster species.     

Nickel‐Catalyzed Decarboxylative Difluoroalkylation of α,β‐Unsaturated Carboxylic Acids

The first example of nickel‐catalyzed decarboxylative fluoroalkylation of α,β‐unsaturated carboxylic acids has been developed with commonly available fluoroalkyl halides. This novel transformation has demonstrated broad substrate scope, excellent functional‐group tolerance, mild reaction conditions, and excellent stereoselectivity. Mechanistic investigations indicate that a fluoroalkyl radical is involved in the catalytic cycle.     

An Enantio‐ and Diastereoselective Chemoenzymatic Synthesis of α‐Fluoro β‐Hydroxy Carboxylic Esters

The trans‐o‐hydroxybenzylidene pyruvate aldolase‐catalysed reactions between fluoropyruvate and many (hetero)aromatic aldehydes yield aldol adducts without subsequent dehydration. Treatment of the reaction products with hydrogen peroxide yields the corresponding syn‐configured α‐fluoro β‐hydroxy carboxylic acids which have >98 % ee. The overall chemoenzymatic approach, in which fluoropyruvate serves as a fluoroacetate equivalent, may be exploited in the synthesis of polar building blocks and fragments with potential value in drug discovery.     

Allyl‐Palladium‐Catalyzed α,β‐Dehydrogenation of Carboxylic Acids via Enediolates

A highly practical and step‐economic α,β‐dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl‐palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)₂⋅2 LiCl as a base in the presence of excess ZnCl₂, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2‐enoic acids allows derivatization by numerous approaches.     

A Study on the Diastereoselective Synthesis of α‐Fluorinated β3‐Amino Acids by α‐Fluorination

The treatment of a β³‐amino acid methyl ester with 2.2 equiv. of lithium diisopropylamide (LDA), followed by reaction with 5 equiv. of N‐fluorobenzenesulfonimide (NFSI) at ?78° for 2.5 h and then 2 h at 0°, gives syn‐fluorination with high diastereoisomeric excess (de). The de and yield in these reactions are somewhat influenced by both the size of the amino acid side chain and the nature of the amine protecting group. In particular, fluorination of N‐Boc‐protected β³‐homophenylalanine, β³‐homoleucine, β³‐homovaline, and β³‐homoalanine methyl esters, 5 and 9 – 11 , respectively, all proceeded with high de (>86% of the syn‐isomer). However, fluorination of N‐Boc‐protected β³‐homophenylglycine methyl ester ( 16 ) occurred with a significantly reduced de. The use of a Cbz or Bz amine‐protecting group (see 3 and 15 ) did not improve the de of fluorination. However, an N‐Ac protecting group (see 17 ) gave a reduced de of 26%. Thus, a large N‐protecting group should be employed in order to maximize selectivity for the syn‐isomer in these fluorination reactions.     

Synthesis of 3‐(2‐hydroxy‐1‐phenylethyl)‐ and 3‐(2‐hydroxy‐2‐phenylethyl)adenine,DNA adducts derived from styrene

3‐(2‐Hydroxy‐2‐phenylethyl)‐ and 3‐(2‐hydroxy‐1‐phenylethyl)adenine, DNA adducts derived from styrene, along with their 9‐substituted analogues were prepared by alkylation of 8‐bromoadenine with corresponding allyl‐protected bromohydrins followed by a new deallylation procedure using tetrakis(triphenylphosphine)palladium catalyzed reductive cleavage by poly(methylhydrosiloxane) in the presence of p‐toluenesulphonic acid. This novel procedure proved to be useful for purine derivatives, which were resistant to other deallylation protocols. Structure of positional isomers was assigned using 2D NMR experiments HMBC and HMQC.     

N1‐(4‐tert‐Butyl­phenyl)‐N2‐hydroxy‐α‐oxo‐α‐phenyl­acet­amidine and N2‐hydroxy‐N1‐(4‐nitro­phenyl)‐α‐oxo‐α‐phenyl­acet­amidine hemihydrate

In the title compounds, C₁₈H₂₀N₂O₂, (I), and C₁₄H₁₁N₃O₄·0.5H₂O, (II), respectively, the oxime groups have an E configuration. In (I), the mol­ecules exist as polymers bound by intermolecular C—H⋯O and O—H⋯N hydrogen bonds around inversion centres. In (II), intermolecular OW—H⋯N, OW—H⋯O and O—H⋯OW interactions stabilize the molecular packing.     

Enantioselective 1,4‐Addition Reaction of α,β‐Unsaturated Carboxylic Acids with Cycloalkanones Using Cooperative Chiral Amine–Boronic Acid Catalysts

An enantioselective 1,4‐addition of α,β‐unsaturated carboxylic acids with cycloalkanones has been developed by using chiral amine–boronic acid cooperative catalysts. In the presence of a chiral amine and boronic acid, cycloalkanones and carboxylic acids are activated as chiral enamines and mixed anhydrides, respectively. The corresponding 1,4‐adducts are obtained in high yield with high enantioselectivity. Furthermore, subsequent oxylactonization of the 1,4‐adducts gives spirolactones with high diastereoselectivity.     

A Novel Diastereoselective Synthesis of 6‐Aryl‐5‐hydroxy‐2,3‐dihydropyrano[2,3‐c]pyrazol‐4(1H)‐ones

A novel one‐pot diastereoselective synthesis of trans‐6‐aryl‐5‐hydroxy‐2,3‐dihydro[2,3‐c]pyrazol‐4(1H)‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h is described via the Darzens condensation reaction of 2‐chloro‐1‐(5‐hydroxy‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)ethanone ( 2 ) with different aromatic aldehydes in aqueous basic medium. The structures of the compounds prepared were determined by analytical and spectral analyses.