Organocatalytic asymmetric Michael-type/Wittig reaction of phosphorus ylides: synthesis of chiral α-methylene-δ-ketoesters

An asymmetric Michael-type reaction of phosphorus ylides and α,β-unsaturated ketones under the catalysis of a chiral ion pair catalyst has been described. The ion pair catalyst containing a chiral counteranion was prepared by simply mixing 9-amino-(9-deoxy)-epi-quinine with l-N-Boc-proline. The optically active α-methylene-δ-ketoesters could be obtained with good to excellent enantioselectivities (up to 95% ee) under mild reaction conditions.     

Investigation of the reaction of α-thioamides, α-esters and α-nitriles with N-halosuccinimides

Investigation of the reaction of α-thioamides, α-esters and α-nitriles with NBS and NCS is described. The scope of this stereoselective oxidative transformation to the β-haloacrylamides, β-acrylates and β-acrylonitriles has been determined. A mechanistic rationale to explain the observed differences in reactivity between the amide, ester and nitrile series is proposed.     

Three-component and nonclassical reaction of phosphines with enynes and aldehydes: formation of γ-lactones featuring α-phosphorus ylides

Inverted carbenoid species, generated from attack of phosphines at the α(δ')-carbon of hex-2-en-4-ynedioic acid dialkyl esters, react with aldehydes to give γ-lactones possessing an α-phosphorus ylide moiety.     

Carbene catalyzed umpolung of α,β-enals: a reactivity study of diamino dienols vs. azolium enolates,and the characterization of advanced reaction intermediates

Since their discovery by Bode and Glorius in 2004, N-heterocyclic carbene catalyzed conjugate umpolung reactions of α,β-enals have been postulated to involve the formation of diamino dienols (“homoenolates”) and/or azolium enolates (“enolates”), typically followed by addition to electrophiles, e.g. Michael-acceptors. In this article, we provide evidence, for the first time, for the postulated individual and specific reactivity patterns of diamino dienols (γ-C–C-bond formation) vs. azolium enolates (β-C–C-bond formation). Our study is based on the pre-formation of well defined diamino dienols and azolium enolates, and the in situ NMR monitoring of their reactivities towards enone electrophiles. Additionally, reaction intermediates were isolated and characterized, inter alia by X-ray crystallography.     

Microbial deracemization of α-substituted carboxylic acids: control of the reaction path

A novel approach to preparing optically active α-substituted carboxylic acids using the whole cells of Nocardia diaphanozonaria JCM 3208 is described. When 2-phenylthiopropanoic acid and 2-methyl-3-phenylpropanoic acid were subjected to the reaction under aerobic conditions, the oxidation reaction proceeded preferentially rather than deracemization of these substrates. Herein, we report the design of reaction conditions to increase the deracemization activity in preference to oxidation reactions. In addition, we have successfully detected a metabolic intermediate in the reaction mixture of 2-methyl-3-phenylpropanoic acid, which indicates that the deracemization is a competitive reaction against the β-oxidation pathway of fatty acid metabolism.     

Stretching the α-helix: a direct measure of the hydrogen-bond energy of a single-peptide molecule

Atomic force microscopy was used to measure the force required to stretch individual molecules of the peptide cysteine₃–lysine₃₀–cysteine from the α-helical state into a linear chain (approximately 200 pN). The measured force versus peptide elongation was used to calculate the work done in breaking the hydrogen bonds which give rise to the helical structure. The average experimental value of the hydrogen-bond energy (20.2 kJ/mol) is in good agreement with reported theoretical calculations. In addition, the stiffness of individual peptides was measured directly using a force modulation technique and found to vary from approximately 0.005–0.012 N/m during elongation.     

Organocatalytic direct asymmetric vinylogous Michael reaction of an α,β-unsaturated γ-butyrolactam with enones

An organocatalytic asymmetric direct vinylogous Michael addition of α,β-unsaturated γ-butyrolactam to enones has been achieved with a simple bifunctional thiourea-tertiary amine catalyst, affording the γ-substituted butyrolactam products with high diastereo- and enantioselectivity (up to >40:1 dr and 94-99% ee).     

Photoaddition reactions of azomethine ylides generated from α-aminonitriles to fullerene C60: Formation of fulleropyrrolidines and reaction efficiencies changes depending on reaction conditions

Photoaddition reactions of C₆₀ with both (trimethylsilyl)methyl and either benzyl or phenethyl group containing α-aminonitriles were carried out to explore how product distributions and reaction efficiencies can be influenced by reaction solvent systems. The results show that photoreactions produce both trimethylsilyl- and cyano group containing fulleropyrrolidines as a major (or exclusive) product. Especially, photoreactions performed in either EtOH containing solution or oxygenated environment take place with a much more efficient manner.     

Mechanisms of the α,α-diphenylprolinol trimethylsilyl ether-catalyzed enantioselective aza-Michael reaction

Depending on the nature of the aza-Michael donor, the C-N bond formation in the α,α-diphenylprolinol trimethylsilyl ether-catalyzed aza-Michael reactions was found to proceed via either (i) an iminol intermediate in a stepwise reaction, or (ii) a concerted reaction. This is contrary to the commonly proposed iminium mechanism for organocatalyst-catalyzed aza-Michael reactions. The iminol intermediate is formed from the reaction between the catalyst and the amine (Michael donor). These proposed mechanisms are able to account for the experimentally observed product enantioselectivity.     

Kinetic Study on Models of the Noncatalyzed Reaction Between α, ω -Dicarboxypolyamide-11 and α, ω -Dihydroxypolyoxyalkylenes

The kinetics of the noncatalyzed reaction between α, ω -dicarboxypoly-amide-11 and α, ω -dihydroxypolyoxyalkylenes is investigated by using the reactions of 11-dodecylamidoundecanoic acid with 1-dodecanol, 2-tridecanol, α-dodecyl-ω-hydroxypolyoxyethylene or α-dodecyl-ω;-hydroxypolyoxypropylene as models. Kinetic data fit a 3rd overall order (2 in acid and 1 in alcohol). Rate constants and activation parameters are determined and compared.     

Kinetic studies of the copolymerisation of styrene and α-methylstyrene. The use of radiotracers to circumvent the effect of ceiling temperature

Styrene (M₁) and ¹⁴C-labelled α-methylstyrene (M₂) have been copolymerised in the temperature range 40 to 105°C, under conditions where [M₁] ⪢ [M₂]. Under these circumstances, the effect of the low ceiling temperature of M₂ was circumvented in deriving a value of the reactivity ratio r₁. The Arrhenius plot of r₁ was linear. Values of r₁ determined under more conventional conditions, where [M₁] ≈ [M₂], have been found to deviate further from this Arrhenius line as the temperature is increased; this illustrates the effect of ceiling temperature under these latter conditions and the unreliability of such values of r₁ when comparing reactivities.     

Synthesis of α-alkoxyalkyltributyllead compounds via the reaction of tributylplumbyllithium with α-chloroethers,and the conjugate addition of tributylplumbyllithium to enones

α-Alkoxyalkyltributylleads 1 were prepared from the reaction of tributylplumbyllithium with α-chloroethers 2. This procedure is more convenient than the conventional method which involves transmetallation from the corresponding α-alkoxyalkyltrialkyltin. Tributylplumbyllithium was also used for the synthesis of β-oxo-organolead 4.     

Chiral guanidine-catalyzed asymmetric direct vinylogous Michael reaction of α,β-unsaturated γ-butyrolactams with alkylidene malonates

The asymmetric direct vinylogous Michael reaction of α,β-unsaturated γ-butyrolactams with alkylidene malonates has been developed. Various 5-substituted 3-pyrrolidin-2-ones were obtained in high yields (up to 93%) with excellent stereoselectivities (up to 94% ee, 95 : 5 dr), using a novel bifunctional C(1)-symmetric guanidine organocatalyst embodied a secondary amine subunit.     

Chemo,regio and stereoselectivity in the reaction of p-bromobenzaldehyde with α-ethoxycrotyltributyltin

The reaction of p-bromobenzaldehyde (1) with α-ethoxycrotyltributyltin (2) has proved amenable to control in terms of chemo, regio and stereochemistry, using appropriate experimental conditions, namely Pd(PPh₃)₄ catalysis, BF₃.Et₂O catalysis or simple heating. In the latter case, a dramatic kinetic effect has been observed: 2E has been proved to be much more reactive (and much more stereoselective) than 2Z.     

Investigating the reaction mechanism and organocatalytic synthesis of α,α'-dihydroxy ketones

A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate α,α'-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used. Firstly, (13)C labelled lithium hydroxypyruvate was synthesised and used to establish where hydroxypyruvate is incorporated in the product. In separate experiments reaction intermediates were also successfully intercepted and structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS. These studies indicated that two mechanisms appear to be operating, one involving the addition of the tertiary amine catalyst to hydroxypyruvate, the other an aldol-based mechanism. Since the first mechanism may enable facial stereodifferentiation in the addition of intermediates to the aldehyde, a preliminary study on the use of chiral catalysts was performed and the first asymmetric organocatalytic synthesis of α,α'-dihydroxy ketones in aqueous media achieved, in up to 50% ee, using a quinine ether catalyst.