Jadwiga Gajewy

Recent Progress in Lewis Base Activation and Control of Stereoselectivity in the Additions of Trimethylsilyl Nucleophiles

Trimethylsilyl nucleophiles (Me3SiNu), with silicon atoms attached to carbon, nitrogen, oxygen, or sulfur atoms, have long been recognized as effective alternatives for proton nucleophiles (HNu) in addition reactions to such electrophiles as aldehydes, ketones, imines, oxiranes, aziridines, nitrones, and polar conjugated systems. The number of examples of such additions has been growing steadily over the past 40 years, while the availability of trimethylsilyl nucleophiles was on the rise and new methods of transformation of silylated pronucleophiles into active nucleophiles were emerging. The interest in Me3SiNu additions was stimulated by the properties of the silicon atom, allowing the generation of active nucleophilic species (Nu), under different conditions in comparison to HNu sources. Activation of Me3SiNu by a Lewis base is primarily due to the affinity of silicon to fluorine or oxygen, facilitating the formation of a reactive pentacoordinate or hexacoordinate silicon intermediate, whereas HNu activation requires Brønsted or Lewis basemediated proton abstraction. Although activation of Me3SiNu and HNu may frequently be carried out with the same catalyst, deprotonation of weakly acidic carbon nucleophiles by strong bases in certain cases may be incompatible with the reaction conditions or with certain functional groups. Desilylative nucleophile activation occurs smoothly under catalytic conditions. Either 1,2-, 1,3-, or 1,4-additions can be carried out with trimethylsilyl nucleophiles, as shown in Scheme 1. The catalytic effect of the fluoride ion as well as polar N-oxide, P-oxide, and S-oxide bonds can be correlated with the dissociation energies of the Si-F and Si-O bonds (Figure 1), which are among the strongest single bonds and much stronger than the corresponding C-F and C-O bonds. Either anionic or neutral Lewis bases are suitable for activation of silylated nucleophiles. Both inorganic (especially CsF) and organic fluorides (most frequently tetra-nScheme 1. Catalytic Nucleophilic 1,2-Additions of Me3SiNu to Aldehydes, Ketones, and Imines (a) or to Epoxides and Aziridines (b), 1,3-Addition to Nitrones (c), and 1,4Additions to r, -Unsaturated Carbonyl Compounds (d) and Nitroalkenes (e) Chem. Rev. 2008, 108, 5227–5252 5227

Fine tuning of molecular and supramolecular properties of simple trianglimines – the role of the functional group

Chiral, triangular poly-azamacrocycles (trianglimines) readily available from enantiomerically pure trans-1,2-diaminocyclohexane and various aromatic dialdehydes, differ in their nature and substitution pattern. The highly symmetrical macrocycle having two electron-donating groups attached to the aryl moieties is formed under thermodynamic control that fulfilled the so called entropy of symmetry rule. Conversely, from the 2-nitroterephthaldehyde a kinetic product of trivial C1 symmetry is solely obtained, whereas from 2-methoxyterepthaldehyde a mixture of C3- and C1-symmetrical macrocycles are formed. The factors that contribute to the mechanism of the macrocycle formation were determined on the basis of an experimental/theoretical approach. The non-symmetrical structure of the macrocycle resulted from a symmetrical intermediate that appeared during cyclocondensation. The chiroptical properties of the trianglimines were studied by means of experimental ECD and VCD methods supported by quantum-chemical calculations. The nitro-substituted trianglimine appeared to be a simple, low molecular weight supergelator forming in polar media of stable chiral organogels. The structure of the gel is affected by the nature and chirality of the dopant. The hexaimine macrocycles after reduction of the CN imine bonds formed trianglamines – useful chiral ligands in stereoselective synthesis. The Zn–trianglamine complexes were employed as catalysts for asymmetric hydrosilylation of prochiral ketones, providing products of enantiomeric excess up to 98%. This remains the best result obtained for Zn–diamine catalysed asymmetric hydrosilylation of ketones so far.

Double helicity induction in chiral bis(triphenylacetamides)

A combination of experimental methods (ECD, X-ray diffraction) and theoretical calculations allowed the description of chirality transfer in bis(triphenylacetamides). For the first time it has been shown that effective helicity induction in a trityl chromophore is not only due to the presence of stereogenic center(s) but is also caused by other chirality inductors such as an axis of chirality. For all experimental and computed ECD spectra a uniformly identical sequence of signs of the Cotton effects has been found: negative at around 215 nm and positive below 200 nm. This result can only be explained by the dependence of the ECD spectra on the R absolute configuration of the proximal stereogenic element. The chirality transfer is achieved through a series of weak intramolecular interactions. Helicities of the trityl chromophores and their propeller shapes are influenced by the structure of the chiral inductor and the steric hindrance at amide nitrogen atoms. The stereogenic centers in the diamide unit act independently as chirality inductors and the direct trityl⋯trityl interactions are only rarely observed. Characteristic for the investigated crystals is the complete hindrance of the amide NH groups and their inability to be involved in any intermolecular interactions as well as their highly restricted ability for the formation of intramolecular hydrogen bonds. This results from the presence of Tr groups, which act as supramolecular NH protecting groups, especially when attached to the rigid carbocycles.

Specific Noncovalent Association of Chiral Large-Ring Hexaimines: Ion Mobility Mass Spectrometry and PM7 Study.

Ion mobility mass spectrometry and PM7 semiempirical calculations are effective complementary methods to study gas phase formation of noncovalent complexes from vaselike macrocycles. The specific association of large-ring chiral hexaimines, derived from enantiomerically pure trans-1,2-diaminocyclohexane and various isophthaldehydes, is driven mostly by CH-π and π-π stacking interactions. The isotrianglimine macrocycles are prone to form two types of aggregates: tail-to-tail and head-to-head (capsule) dimers. The stability of the tail-to-tail dimers is affected by the size and electronic properties of the substituents at the C-5 position of the aromatic ring. Electron-withdrawing groups stabilize the aggregate, whereas bulky or electron-donating groups destabilize the complexes.