Catalytic Asymmetric β-Oxygen Elimination

A catalytic enantioselective β-O-elimination reaction is reported in the form of a zirconium-catalyzed asymmetric opening of meso-ketene acetals. Furthermore, a regiodivergent β-O-elimination is demonstrated. The reaction proceeds under mild conditions, at low catalyst loadings, and produces chiral monoprotected 1,2-diol building blocks in good yield and enantiomeric excess. The combination with a Mitsunobu reaction then gives access to all 1,2-diol stereoisomers and trans-1,2-aminoalcohols in high enantiomeric purity. A stereochemical analysis supported by DFT calculations reveals that a high selectivity in the hydrozirconation step is also important for achieving high enantioselectivity, although it does not constitute the asymmetric step. This insight is crucial for the future development of related asymmetric β-elimination reactions.

Chloride Ion Catalysed Rearrangement, and Isotope Exchange of the Isomeric Methylallyl Chlorides in Acetonitrile

<p><b>The bromide ion catalysed rearrangement reaction of ⍺-methylallyl bromide in acetone was studied by England and Hughes and assigned an S[n]2' mechanism, and this was the only isomeric rearrangement reaction proceeding by this mechanism which had been thoroughly investigated. 79,120 The kinetics and mechanism of the chloride ion catalysed isomeric rearrangement reactions of ⍺-and ɣ-methylallyl chloride in acetonitrile have now been investigated and an S[n]2' mechanism has been assigned to these reactions, various other possible mechanisms having been excluded. The kinetics and mechanics of the isotope exchange reactions of the two isomers in acetonitrile have also bean studied and these reactions have been assigned en S[n]2 mechanism. The isotope exchange reactions of both the methylallyl bromides and the methylallyl chlorides in acetone were studied by England and Hughes, the reaction medium being unfavourable for a study of the S[n]2' reactions of the latter substrates. A comparison of the kinetic data for the rearrangement end Isotope exchange reactions of the methylallyl chlorides in acetonitrile with that for the corresponding reactions of the methylallyl bromides in acetone la made. The two systems are similar in behaviour as may be seen from the data tabulated below.</b></p> <p>Substrate Mechanism K2 (25° C) Δ H°Δ S° (M⁻¹ sec.⁻¹) (kcal.mole⁻¹) (cal.deg.⁻¹ mole⁻¹)⍺-methylallyl chloride S[n]2 2.87X10⁻⁶ 20.8-13.9⍺-methylallyl chloride S[n]2'1.33X10⁻⁸ 24.2-13.4ɣ-methylallyl chlorideS[n]2 3.15X10⁻⁴ 18.8-11.6ɣ-methylallyl chloride S[n]2' 5.31X10⁻⁹ 24.3-14.9⍺-methylallyl bromide S[n]2 8.79X10⁻⁴ 15.9-19.1⍺-methylallyl bromide S[n]2' 1.49X10⁻⁵ 18.8-17.7ɣ-methylallyl bromide S[n]2 1.41X10⁻¹ 14.1-15.0⍺-methylallyl chloride S[n]2 2.30X10⁻⁷ 19.9-22.1ɣ-methylallyl chloride S[n]2 2.88X10⁻⁵ 15.8-26.2A comparison of the kinetic data for the isotope exchange reactions of the methylallyl chlorides in acetonitrile and acetone is also made. England and Hughes' data for the latter solvent is shown above. Relative rates of nucleophilic attack at saturated carbon, π-bonded carbon and hydrogen are discussed for these substrates, a minor concurrent elimination reaction accompanying the S[n]2' reaction of ⍺-methylallyl chloride in acetonitrile providing information on the latter. The nucleophilic reactivity of the halide ions is much greater for attack at a saturated carbon atom than for attack at a π-bonded carton atom, while toward hydrogen these ions are very weak nucleophiles as shown by the rate ratios given below for the chloride ion catalysed reactions of ⍺-methylallyl chloride in acetonitrile.</p> <p>[see thesis pdf for formula]In the absence of chloride ions a slow surface-catalysed elimination reaction takes place which promotes hydrogen chloride catalysed rearrangement. The addition of 0.05M Et4 NCl prevents the latter reaction from occurring and gives a rata ratio of 5.5 for the chloride ion catalysed and surface-catalysed elimination reactions. By comparison with other dipolar aprotic solvents, acetonitrile appears to be particularly suitable for slow reactions requiring prolonged reaction times at elevated temperatures. Acetone, as mentioned above, and both dimethyl sulphoxide and dimethylformamide were found to be unsuitable for S[n]2' studies, the latter two being: Investigated during the search for a suitable solvent in which to study the reactions of the methylallyl chlorides.</p>

Chloride Ion Catalysed Rearrangement, and Isotope Exchange of the Isomeric Methylallyl Chlorides in Acetonitrile

<p><b>The bromide ion catalysed rearrangement reaction of ⍺-methylallyl bromide in acetone was studied by England and Hughes and assigned an S[n]2' mechanism, and this was the only isomeric rearrangement reaction proceeding by this mechanism which had been thoroughly investigated. 79,120 The kinetics and mechanism of the chloride ion catalysed isomeric rearrangement reactions of ⍺-and ɣ-methylallyl chloride in acetonitrile have now been investigated and an S[n]2' mechanism has been assigned to these reactions, various other possible mechanisms having been excluded. The kinetics and mechanics of the isotope exchange reactions of the two isomers in acetonitrile have also bean studied and these reactions have been assigned en S[n]2 mechanism. The isotope exchange reactions of both the methylallyl bromides and the methylallyl chlorides in acetone were studied by England and Hughes, the reaction medium being unfavourable for a study of the S[n]2' reactions of the latter substrates. A comparison of the kinetic data for the rearrangement end Isotope exchange reactions of the methylallyl chlorides in acetonitrile with that for the corresponding reactions of the methylallyl bromides in acetone la made. The two systems are similar in behaviour as may be seen from the data tabulated below.</b></p> <p>Substrate Mechanism K2 (25° C) Δ H°Δ S° (M⁻¹ sec.⁻¹) (kcal.mole⁻¹) (cal.deg.⁻¹ mole⁻¹)⍺-methylallyl chloride S[n]2 2.87X10⁻⁶ 20.8-13.9⍺-methylallyl chloride S[n]2'1.33X10⁻⁸ 24.2-13.4ɣ-methylallyl chlorideS[n]2 3.15X10⁻⁴ 18.8-11.6ɣ-methylallyl chloride S[n]2' 5.31X10⁻⁹ 24.3-14.9⍺-methylallyl bromide S[n]2 8.79X10⁻⁴ 15.9-19.1⍺-methylallyl bromide S[n]2' 1.49X10⁻⁵ 18.8-17.7ɣ-methylallyl bromide S[n]2 1.41X10⁻¹ 14.1-15.0⍺-methylallyl chloride S[n]2 2.30X10⁻⁷ 19.9-22.1ɣ-methylallyl chloride S[n]2 2.88X10⁻⁵ 15.8-26.2A comparison of the kinetic data for the isotope exchange reactions of the methylallyl chlorides in acetonitrile and acetone is also made. England and Hughes' data for the latter solvent is shown above. Relative rates of nucleophilic attack at saturated carbon, π-bonded carbon and hydrogen are discussed for these substrates, a minor concurrent elimination reaction accompanying the S[n]2' reaction of ⍺-methylallyl chloride in acetonitrile providing information on the latter. The nucleophilic reactivity of the halide ions is much greater for attack at a saturated carbon atom than for attack at a π-bonded carton atom, while toward hydrogen these ions are very weak nucleophiles as shown by the rate ratios given below for the chloride ion catalysed reactions of ⍺-methylallyl chloride in acetonitrile.</p> <p>[see thesis pdf for formula]In the absence of chloride ions a slow surface-catalysed elimination reaction takes place which promotes hydrogen chloride catalysed rearrangement. The addition of 0.05M Et4 NCl prevents the latter reaction from occurring and gives a rata ratio of 5.5 for the chloride ion catalysed and surface-catalysed elimination reactions. By comparison with other dipolar aprotic solvents, acetonitrile appears to be particularly suitable for slow reactions requiring prolonged reaction times at elevated temperatures. Acetone, as mentioned above, and both dimethyl sulphoxide and dimethylformamide were found to be unsuitable for S[n]2' studies, the latter two being: Investigated during the search for a suitable solvent in which to study the reactions of the methylallyl chlorides.</p>

Entrapment of Phenylalanine Ammonia-Lyase in Nanofibrous Polylactic Acid Matrices by Emulsion Electrospinning

Immobilization of the recombinant, plant-derived Petroselinum crispum phenylalanine ammonia lyase (PcPAL) in electrospun matrices have the potential to create promising, easy-to-use biocatalysts. Polylactic acid (PLA) a biologically inert, commercial biopolymer, was chosen as the material of the carrier system. PLA could be electrospun properly only from water-immiscible organic solvents, which limits its application as a carrier of sensitive biological objects. The emulsion electrospinning is a proper solution to overcome this issue using non-ionic emulsifiers with different hydrophilic-lipophilic balance (HLB) values. The stabilized emulsion could protect the sensitive PcPAL dissolved in the aqueous buffer phase and improve fiber formation, plus help to keep the biocatalytic activity of enzymes. In this study, the first approach is described to produce PLA nanofibers containing PcPAL enzymes by emulsion electrospinning and to use the resulted biocatalyst in the ammonia elimination reaction from l-phenylalanine.