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We report a systematic study of the allylation of ortho-substituted benzaldehydes under catalysis of a Lewis base (N,N-dioxide), a Lewis acid (Keck allylation), and a Bronsted acid. ortho-Halobenzaldehydes were used as the aldehydic substrates, and special attention was paid to ortho-vinyl and alkynyl benzaldehydes, which might serve as interesting synthons for the preparation of more complex chiral compounds. Similar enantioselectivities were achieved under catalytic conditions. In the case of ortho-halobenzaldehydes, Lewis base catalysis proved to be more efficient, and the highest asymmetric induction for allylation of ortho-fluorobenzaldehyde reached 82 % ee, which is comparable to other used catalytic conditions. In cases of ortho-vinylbenzaldehyde, the Keck allylation provided the product in 88 % ee. An enantioenriched homoallylic alcohol was used as the starting material for the synthesis of a sertraline intermediate.

Four bis(tetrahydroisoquinoline) N,N′-dioxides were used as catalysts for the epoxide ring opening with tetrachlorosilane under various conditions. A strong solvent effect on asymmetric induction was observed for each of the used catalysts. The highest achieved asymmetric induction for the opening of meso-stilbene oxide was 69% ee. Regarding the cycloalkene oxides, 56% ee was obtained in the reaction with cyclooctene oxide.

A novel class of chiral superbases derived from the 2,2'-bipyridyl-N,N'-dioxide skeleton are presented. Combined experimental and theoretical data reveal that their proton affinities are on the order of 1050 kJ mol(-1), with protonation occurring at the oxygen atoms in a chelating manner. In the free bases, the oxygen atoms form a strongly polar binding site hidden in a hydrophobic envelope formed by the hydrocarbon backbone of the superbases. This chiral molecular structure can entrap polar intermediates or polarized transition structures and stabilize them in nonpolar solvents. Specifically, this mode of catalysis is shown for the coupling of benzaldehyde and allyltrichlorosilane.

Unsymmetrically 3,3'-substituted axially chiral bis(tetrahydroisoquinoline) N,N'-dioxides can be prepared in just three steps. They exhibit unique catalytic activity (turnover frequency, enantioselectivity, substrate scope) in the asymmetric allylation of aromatic aldehydes (up to 96% ee). The product of the enantioselective allylation of benzaldehyde served as a building block for the preparation of an intermediate useful in the enantioselective synthesis of diospongines.

Asymmetric allylation of aromatic aldehydes 1 with allyltrichlorosilane (2) can be catalyzed by new terpene-derived bipyridine N,N′-dioxides 12–15 and an axially chiral biisoquinoline dioxide 17b with good enantioselectivities. Dioxides have been found to be more reactive catalysts than their monooxide counterparts.

The effect of halogen-to-hydrogen bond substitution on the binding energetics and biological activity of a human aldose reductase inhibitor has been studied using X-ray crystallography, IC50 measurements, advanced binding free energy calculations, and simulations. The replacement of Br or I atoms by an amine (NH2) group has not induced changes in the original geometry of the complex, which made it possible to study the isolated features of selected noncovalent interactions in a biomolecular complex.

The asymmetric catalytic alkylation of ortho-substituted benzaldehydes proceeds under Lewis basic and acidic catalyst conditions to give homoallylic alcohols.

Axially chiral bipyridine N , N ′-dioxides (Lewis basic organocatalysts) are easily accessible in three steps from commercially available material. The key step of this reaction sequence is cobalt-catalyzed heterocyclotrimerization of 1-pyridyl-1,7-octadiynes with nitriles. Our effort was focused on the synthesis of unsymmetrically substituted bipyridines. The scope of the cyclotrimerization reaction was tested under thermal and microwave conditions. Two of the synthesized bipyridine N , N ′-dioxides were successfully resolved into enantiomers and tested in enantioselective allylation of aldehydes.

The bifunctional allyldisilane (II) undergoes a two-step triple allylation sequence with two aldehydes to give all-cis trisubstituted tetrahydrofurans.

Two earlier synthesized (compounds Ia) and two novel (compounds Ib) axially chiral N-oxide catalysts are tested in the ring opening of epoxides.

Three for the price of two: A bifunctional allyldisilane undergoes a two-step triple allylation sequence with pairs of aldehydes to give all-cis trisubstituted tetrahydrofurans in excellent enantio- and diastereoselectivity (see scheme). The first allylation step, which sets up the key stereogenic centres, is catalysed by a chiral Lewis base.

Unsymmetrically 3,3'-substituted axially chiral bis(tetrahydroisoquinoline) N,N'-dioxides can be prepared in just three steps. They exhibit unique catalytic activity (turnover frequency, enantioselectivity, substrate scope) in the asymmetric allylation of aromatic aldehydes (up to 96% ee). The product of the enantioselective allylation of benzaldehyde served as a building block for the preparation of an intermediate useful in the enantioselective synthesis of diospongines.

Axially chiral bipyridine N , N ′-dioxides (Lewis basic organocatalysts) are easily accessible in three steps from commercially available material. The key step of this reaction sequence is cobalt-catalyzed heterocyclotrimerization of 1-pyridyl-1,7-octadiynes with nitriles. Our effort was focused on the synthesis of unsymmetrically substituted bipyridines. The scope of the cyclotrimerization reaction was tested under thermal and microwave conditions. Two of the synthesized bipyridine N , N ′-dioxides were successfully resolved into enantiomers and tested in enantioselective allylation of aldehydes.