Enantiomeric excess | EPFL Graph Search

In stereochemistry, enantiomeric excess (ee) is a measurement of purity used for chiral substances. It reflects the degree to which a sample contains one enantiomer in greater amounts than the other. A racemic mixture has an ee of 0%, while a single completely pure enantiomer has an ee of 100%. A sample with 70% of one enantiomer and 30% of the other has an ee of 40% (70% − 30%). Enantiomeric excess is defined as the absolute difference between the mole fraction of each enantiomer: where In practice, it is most often expressed as a percent enantiomeric excess. The enantiomeric excess can be determined in another way if we know the amount of each enantiomer produced. If one knows the moles of each enantiomer produced then: Enantiomeric excess is used as one of the indicators of the success of an asymmetric synthesis. For mixtures of diastereomers, there are analogous definitions and uses for diastereomeric excess and percent diastereomeric excess. As an example, a sample with 70 % of R isomer and 30 % of S will have a percent enantiomeric excess of 40. This can also be thought of as a mixture of 40 % pure R with 60 % of a racemic mixture (which contributes half 30 % R and the other half 30 % S to the overall composition). If given the enantiomeric excess of a mixture, the fraction of the main isomer, say R, can be determined using and the lesser isomer . A non-racemic mixture of two enantiomers will have a net optical rotation. It is possible to determine the specific rotation of the mixture and, with knowledge of the specific rotation of the pure enantiomer, the optical purity can be determined. optical purity (%) = [α]_ ()/[α]_ () · 100 Ideally, the contribution of each component of the mixture to the total optical rotation is directly proportional to its mole fraction, and as a result the numerical value of the optical purity is identical to the enantiomeric excess. This has led to informal use the two terms as interchangeable, especially because optical purity was the traditional way of measuring enantiomeric excess.

Catalytic Enantioselective Transformations with Chiral Cyclopentadienyl Ruthenium(II) Complexes

Sung Hwan Park

The chemistry of cyclopentadienyl ruthenium(II) complexes plays an important role in ruthenium catalysis because of its high potential for various transformations. However, asymmetric catalysis with chiral cyclopentadienyl ruthenium(II) complexes is still at an infant stage, but rapidly developing because of its expected impact on multiple enantioselective applications. This thesis discusses the synthesis of a novel class of chiral cyclopentadienyl ligands, which can be readily accessed by a two-step process from alpha, beta-unsaturated aldehydes and cyclopentadiene. The novel C2-symmetric chiral cyclopentadienyl ligands were complexed with ruthenium(II) and successfully applied in asymmetric catalysis. The cyclopentane-fused CpxRu complex enables the enantioselective synthesis of benzonorcaradienes by coupling of oxa-benzonorbornadienes with internal alkynes in high enantioselectivity (up to 97.5:2.5 er). The reaction mechanism was investigated by computational studies and control experiments. The chiral cyclopentadienyl ruthenium(II) complexes show promising results for other transformations. An alkylative cycloetherification of allenols and aryl vinyl ketones was investigated using binaphthyl-derived chiral cyclopentadienyl ruthenium(II) complex. After an initial optimization study, allenol and phenyl vinyl ketone gave the desired enantio-enriched cyclic ether with a promising enantioselective ratio of 90:10. Furthermore, preliminary studies were undertaken for the [2+1] cycloaddition of enynes via ruthenium vinyl carbenes. Model substrate, 1,6-enyne, delivered the desired enantio-enriched bicyclo[3.1.0]hexane in a good yield of 72% (E:Z = 1.6:1), with enantiomeric ratios of 72.5:27.5 and 63.5:36.5 for the E- and Z-isomer, respectively.

EPFL2020

New Acetylene Chemistry

Davinia Fernández González

This thesis is divided in seven main chapters including an introduction about the state of the art in the field, four main chapters describing the main part of the work, a short insight on the implications of the presented results for other research projects and a conclusion. The experimental procedures as well as spectroscopic data are grouped in a special section at the end of the thesis. Acetylenes are versatile intermediates in chemistry, biochemistry and material sciences. The functionalization of alkynes by addition reactions to carbonyl compounds, cycloaddition or coupling reactions using metal catalysis for example make them excellent building blocks for the construction of organic molecules. Furthermore, there are several examples of natural products and drugs containing an acetylene group. Usually, they are synthesized by addition of an acetylide anion to an electrophile. However, the reverse approach (Umpolung of the reactivity) via an electrophilic acetylene synthon has been more rarely used. This constitutes a serious limitation, in particular when considering that "classical" C-C bond formation is not adequate for the synthesis of quaternary centers containing an acetylene. The subject of this thesis is the development of a new class of alkynylation reactions to access propargylic quaternary centers by using hypervalent iodine reagents for the Umpolung of the normal reactivity of alkynes. We started our studies examining the alkynylation reaction with different β-keto esters using the hypervalent iodine reagent TMS-Ethynyl BenziodoXone (TMS-EBX). The excellent reactivity of this cyclic iodine reagent as alkynylation reagent led to the formation of free acetylene products even in the presence of sterically hindered ester groups. The ethynylation reaction proceeded in good yield using TBAF both as a base and fluoride source with TMS-EBX as alkynylation reagent for cyclic and non-cyclic keto esters. Different hypervalent iodine compounds have been tested for the alkynylation of cyclic keto esters. EBX reagents have shown to be generally more efficient than the established iodonium salts. Based on these first results, we next examined the alkynylation of nitro and cyano esters as well as β-keto amides, which have never been used in the past. We were pleased to see that the developed method was also applicable for these classes of compounds affording the corresponding ethynylated products in good yield. The synthetic potential of propargylic nitro compounds bearing free acetylenes was demonstrated by their transformation into propargylic triazoles, hydroxylamines and protected amines, as well as into allyl amines in good yield. We have investigated next, the asymmetric version of the alkynylation reaction under organocatalytic phase-transfer conditions. An enantiomeric excess of 40% has been obtained for cyclic keto esters using cinchona-derived catalysts. Phosphonium catalysts gave an improved enantiomeric excess (51% ee). Higher asymmetric induction has been obtained using the binaphthyl-derived catalysts developed by Maruoka, which has been tested for different substrates to give 12-79% ee. Finally, we have conducted preliminary mechanistic investigations. In situ NMR experiments, isotope labeling and structure-activity relationship studies have allowed us to propose a first crude picture of the catalytic cycle for the alkynylation reaction. In summary, we have reported the first truly general approach for the alkynylation of soft nucleophiles using hypervalent iodine reagents. The developed reaction conditions led to high yields of unprotected acetylenes with cyclic, nitro and linear keto esters as well as keto amides. Furthermore, asymmetric induction was observed using cinchona or binaphthyl derived phase-transfer catalysts (up to 79% ee). This allows a new direct access to chiral acetylene compound in high yields under operationally simple reaction conditions. Future work will be dedicated to the improvement of the enantiomeric excess as well as the scope of the reaction.

EPFL2011

New Acetylene Chemistry

Davinia Fernández González

EPFL2011