Aspects of stereocontrol in the L-Selectride reduction of 4-acyl-1,3-dioxolane derivatives

The application of L-Selectride, either alone or in combination with ZnCl₂, to aryl ketones 1, 8 and 11 resulted in highly anti-stereoselective reduction. In contrast, lactols 22 and 23 gave a moderate syn-preference using L-Selectride alone and a high syn-preference in the presence of ZnCl₂. Uniquely, high anti- stereoselectivity was observed in the reduction of o-anisyl lactol 37 with L-Selectride alone, which was switched to a high syn-preference when ZnCl₂ was present.     

Highly diastereoselective synthesis of 2-substituted-1,3-diols catalyzed by ketoreductases

The stereoselective reduction of α-substituted-β-hydroxy ketones for the preparation of the corresponding optically pure 2-monosubstituted or 2-disubstituted-1,3-diols is described. These transformations proceed in high optical purities and yields. Ketoreductases were able to catalyze the formation of either the syn or the anti diol, depending on the enzyme. By replacing the α-alkyl substituent for an OAc moiety, in low conversion time (≤24 h), ketoreductases catalyzed the formation of the OAc-protected 1,2,3-triol, in high yield and with high optical purity (>99% de, >99% ee). This is a simple and highly stereoselective method for the synthesis of different diastereomers of chiral diols.     

HBF4·OEt2 as a versatile reagent for the Hosomi-Sakurai allylation and Prins cyclization: one-pot synthesis of symmetrical 4-fluorotetrahydropyrans

The synthesis of symmetrical 2,6-disubstituted 4-fluorotetrahydropyran derivatives has been achieved using HBF₄·OEt₂ via a tandem allylation and Prins cyclization. This is a highly efficient and diastereoselective approach for the preparation of 4-fluorotetrahydropyrans in a single step. The use of readily available and easy to handle reagent HBF₄·OEt₂ makes this method simple, convenient and practical.     

Glycine Dimers: Structure,Stability, and Medium Effects

We report a study on different ionization states and conformations of the bimolecular (Gly)₂ system by means of quantum mechanical calculations. Optimized geometries for energy minima of the glycine dimer, as well as relative energies and free energies were computed as a function of the medium: gas phase, nonpolar polarizable solvent, and aqueous solution. The polarizable continuum model was employed to account for solvation effects. Energy calculations were done using the MP2/aug‐cc‐pVTZ and B3LYP/6‐311+G(2df,2p) methods on B3LYP/6‐31+G(d,p) optimized structures (some single‐point energy calculations were also done using the B3PW91 and PBE1KCIS methods). Ionized forms of the glycine dimer (either zwitterion–zwitterion or neutral–zwitterion) are predicted to exist in all media, in contrast to amino acid monomers. In aqueous solution, dimerization is an exergonic process (?4 kcal mol^?1). Thus, according to our results, zwitterion–zwitterion Gly dimers might be abundant in supersaturated glycine aqueous solutions, a fact that has been connected with the structure of α‐glycine crystals but that remains controversial in the literature. Another noticeable result is that zwitterion–zwitterion interactions are substantially underestimated when computed using methods based on density functional theory. For comparison, some calculations for the dimer of the simplest chiral amino acid alanine were done as well and differences to the glycine dimer are discussed.     

Dimeric Capsules Formed by Tetra‐CMPO Derivatives of (Thia)Calix[4]arenes

Thiacalix[4]arene 2 , calix[4]arene 3 a and its tetraether fixed in the cone conformation 3 b form homo‐ and heterodimeric capsules in apolar solvents, which are held together by a seam of NH???O=P hydrogen bonds between carbamoylmethyl phospine oxide functions attached to their wide rim. Their internal volume of ～370 ų requires the inclusion of a suitable guest. Although neutral molecules such as adamantane (derivatives) or tetraethylammonium cations form kinetically stable complexes (¹H‐ and ³¹P‐time scale), the included solvent is rapidly exchanged. The internal mobility of the included tetraethylammonium cation is distinctly higher (ΔG=42.5 and 49.7 kJ mol^?1 for 3 a and 3 b ) than that for similar capsules of tetraurea calix[4]arenes 1 . Mixtures of 1 with 2 , 3 a , or 3 b contain only the two homodimers but the heterodimerization occurs with the tetraloop tetraurea 6 , which cannot form homodimers. Two dimers with cationic guests ( 2? (C₅H₅)₂Co⁺ ?2 and 3 a? Et₃NH⁺ ? H₂O ?3 a ) were confirmed by single‐crystal X‐ray analysis.     

Reductive Dimerization of Triruthenium Clusters Containing Cationic Aromatic N‐Heterocyclic Ligands

The cationic cluster complexes [Ru₃(μ‐H)(μ‐κ²N,C‐L¹ Me)(CO)₁₀]⁺ ( 1 ⁺; HL¹ Me=N‐methylpyrazinium), [Ru₃(μ‐H)(μ‐κ²N,C‐L² Me)(CO)₁₀]⁺ ( 2 ⁺; HL² Me=N‐methylquinoxalinium), and [Ru₃(μ‐H)(μ‐κ²‐N,C‐L³ Me)(CO)₁₀]⁺ ( 3 ⁺; HL³ Me=N‐methyl‐1,5‐naphthyridinium), which contain cationic N‐heterocyclic ligands, undergo one‐electron reduction processes to become short lived, ligand‐centered, trinuclear, radical species ( 1 – 3 ) that end in the formation of an intermolecular C? C bond between the ligands of two such radicals, thus leading to neutral hexanuclear derivatives. These dimerization processes are selective, in the sense that they only occur through the exo face of the bridging ligands of trinuclear enantiomers of the same configuration, as they only afford hexanuclear dimers with rac structures (C₂ symmetry). The following are the dimeric products that have been isolated by using cobaltocene as reducing agent: [Ru₆(μ‐H)₂{μ₆‐κ⁴N₂,C₂‐(L¹ Me)₂}(CO)₁₈] ( 5 ; from 1 ⁺), [Ru₆(μ‐H)₂{μ₆‐κ⁴N₂,C₂‐(L² Me)₂}(CO)₁₈] ( 6 ; from 2 ⁺), and [Ru₆(μ‐H)₂{μ₄‐κ⁸N₂,C₆‐(L³ Me)₂}(CO)₁₈] ( 7 ; from 3 ⁺). The structures of the final hexanuclear products depend on the N‐heterocyclic ligand attached to the starting materials. Thus, although both trinuclear subunits of 5 and 6 are face‐capped by their bridging ligands, the coordination mode of the ligand of 5 is different from that of the ligand of 6 . The trinuclear subunits of 7 are edge‐bridged by its bridging ligand. In the presence of moisture, the reduction of 3 ⁺ with cobaltocene also affords a trinuclear derivative, [Ru₃(μ‐H)(μ‐κ²N,C‐L^3′ Me)(CO)₁₀] ( 8 ), whose bridging ligand (L^3′ Me) results from the formal substitution of an oxygen atom for the hydrogen atom (as a proton) that in 3 ⁺ is attached to the C⁶ carbon atom of its heterocyclic ligand. The results have been rationalized with the help of electrochemical measurements and DFT calculations, which have also shed light on the nature of the odd‐electron species, 1 – 3 , and on the regioselectivity of their dimerization processes. It seems that the sort of coupling reactions described herein requires cationic complexes with ligand‐based LUMOs.     

Dimerisation Process of Silybin‐Type Flavonolignans: Insights from Theory

Natural polyphenols are known to be oxidized by free radicals, which partially explains the antioxidant properties of a number of these compounds. This oxidation may also be used to synthesise new compounds of biological interest, for example, dimers. The present theoretical study describes the existing experimental evidence showing that silybin and dehydrosilybin [natural polyphenols isolated from milk thistle (Silybum marianum)] form dimers regioselectively. Based on DFT calculations, thermodynamic and kinetic values were computed in order to better understand the physicochemical behaviour of these dimerisation processes. Calculations showed that after H‐atom transfer (from polyphenol to radical), dimerisation could proceed in two steps: 1) bond formation and, when possible, 2) tautomerisation reorganisation. The former step is the limiting step, while the latter is crucial for the process to be thermodynamically favourable (ΔG<0). If this rearrangement is impossible then dimerisation is not feasible, or at least becomes a minor process (e.g., dehydrosilybin dimerisation after H‐atom abstraction from the 3‐OH group). This explains the regioselectivity of polyphenol dimerisation.     

Diastereoselective ortho-lithiation of [5]ferrocenophanes

Planarly chiral ferrocene derivatives with bridged cyclopentadienyl rings are interesting ligands in asymmetric catalysis. A planar stereogenic unit is conveniently introduced by diastereoselective ortho-lithiation. The directed lithiation of several [5]ferrocenophane derivatives followed by quenching with chlorodiphenylphosphane led to planarly chiral ligands. The sense of diastereoselection was studied by computational methods. Absolute configuration of methoxy phosphane was determined by single crystal X-ray diffraction study.     

Novel four-component reaction towards diastereoselective synthesis of tetrahydropyrimidinthiones

The first multicomponent synthesis of tetrahydropyrimidinthiones has been realized via the four-component assembly of aromatic aldehyde, enaminone, aromatic amine, and thiourea. The reaction was performed at room temperature and the products were obtained in excellent diastereoselectivity.