Andrei V. Malkov

Asymmetric reduction of imines with trichlorosilane, catalyzed by sigamide, an amino acid-derived formamide: scope and limitations

Enantioselective reduction of ketimines 6-10 with trichlorosilane can be catalyzed by the N-methyl valine-derived Lewis-basic formamide (S)-23 (Sigamide) with high enantioselectivity (< or = 97% ee) and low catalyst loading (1-5 mol %) at room temperature in toluene. The reaction is efficient with ketimines derived from aromatic amines (aniline and anisidine) and aromatic, heteroaromatic, conjugated, and even nonaromatic ketones 1-5, in which the steric difference between the alkyl groups R(1) and R(2) is sufficient. Simple nitrogen heteroaromatics (8a,b,d) exhibit low enantioselectivities due to the competing coordination of the reagent but increased steric hindrance in the vicinity of the nitrogen (8c,e) results in a considerable improvement. Cyclic imines 32d-d exhibited low to modest enantioselectivities.

On the Mechanism of Asymmetric Allylation of Aldehydes with Allyltrichlorosilanes Catalyzed by QUINOX, a Chiral Isoquinoline N-Oxide

Allylation of aromatic aldehydes 1a-m with allyl- and crotyl-trichlorosilanes 2- 4, catalyzed by the chiral N-oxide QUINOX (9), has been found to exhibit a significant dependence on the electronics of the aldehyde, with p-(trifluoromethyl)benzaldehyde 1g and its p-methoxy counterpart 1h affording the corresponding homoallylic alcohols 6g, h in 96 and 16% ee, respectively, at -40 degrees C. The kinetic and computational data indicate that the reaction is likely to proceed via an associative pathway involving neutral, octahedral silicon complex 22 with only one molecule of the catalyst involved in the rate- and selectivity-determining step. The crotylation with (E) and (Z)-crotyltrichlorosilanes 3 and 4 is highly diastereoselective, suggesting the chairlike transition state 5, which is supported by computational data. High-level quantum chemical calculations further suggest that attractive aromatic interactions between the catalyst 9 and the aldehyde 1 contribute to the enantiodifferentiation and that the dramatic drop in enantioselectivity, observed with the electron-rich aldehyde 1h, originates from narrowing the energy gap between the (R)- and (S)-reaction channels in the associative mechanism (22). Overall, a good agreement between the theoretically predicted enantioselectivities for 1a and 1h and the experimental data allowed to understand the specific aspects of the reaction mechanism.

Dynamic Kinetic Resolution in the Asymmetric Synthesis of β‐Amino Acids by Organocatalytic Reduction of Enamines with Trichlorosilane

A new methodology based on the organocatalytic asymmetric hydrosilylation of enamines that allows a direct access to a range of β and β -amino acid derivatives was presented. The results show a successful reduction of aromatic substrates, a sterically more hindered ortho-substituted derivatives, and the thiophenyl analogue exhibiting lower reactivity. Fast enamine-imine equilibration is crucial as imines are chiral but racemic, while α-alkyl β-amino acids can be accessed by the symmetrical Mannich reaction. The α-alkyl derivatives have relative and absolute configuration due to their reduction with LiAlH into a known amino alcohols. Predominant formation of the anti isomer in 3o is consistent with conformation of the imine intermediate in the catalytic reduction.

Enantioselective Baeyer-Villiger oxidation catalyzed by palladium(II) complexes with chiral P,N-ligands.

Asymmetric Baeyer-Villiger reaction of symmetrical cyclobutanones 1a-j with urea-hydrogen peroxide (UHP) can be catalyzed by a complex of Pd(II) and the new terpene-derived P, N-ligand 7. The resulting lactones 2a-j were obtained in high yields and with good enantioselectivity (< or =81% ee).

Asymmetric allylation of aldehydes with allyltrichlorosilane promoted by chiral sulfoxides

Allylation of aldehydes with allyltrichlorosilane in the presence of sulfoxides is reported. The use of excess of (R)-methyl-p-tolylsulfoxide resulted in the formation of the corresponding homoallylic alcohols in good yields and moderate enantiomeric excesses.

Highly Enantio‐ and Diastereoselective Generation of Two Quaternary Centers in Spirocyclopropanation of Oxindole Derivatives.

Spirocyclopropanes: Only one out of eight possible stereoisomers was obtained in the asymmetric cascade cyclopropanation of alkylidene oxindoles with ethyl 2-chloroacetoacetate. Improved catalyst design ensured that spirocyclopropyl oxindoles featuring two quaternary centers were synthesized in high yield and high enantio- and diastereoselectivity (see scheme).

New pyridine-derived N-oxides as chiral organocatalysts in asymmetric allylation of aldehydes

Abstract New chiral pyridine-type N -oxides 5a – e have been synthesized from (+)-α-pinene (+)- 6 in four steps including photochemical oxidation, followed by Krohnke annulation, α-alkylation, and N -oxidation. The methoxy derivative (+)- 5d exhibited the highest enantioselectivity as a catalyst in the title reaction, producing ( S )-(–)- 3 of 68% e.e.

Asymmetric molybdenum(0)-catalyzed allylic substitution

Abstract Application of new ligands ( R )-(−)- 8 , ( S )-(+)- 16 , and ( S )-(+)- 17 to the title reaction ( 1 or 2 → 3 ) led to excellent regio- and enantioselectivities (>30:1; ≤98% ee); although lacking the C 2 -symmetry, the catalysts can be viewed as quasi - C 2 -symmetrical since the single chiral center is sufficient to determine the sense of wrapping of the metal by the ligand.

Vanadium-Catalyzed Asymmetric Epoxidation of Allylic Alcohols in Water

Asymmetric V-catalyzed epoxidation of allylic alcohols can be carried out in water with chiral ligands, which incorporate sulfonamide and hydroxamic acid fragments. Furthermore, the reaction, notorious for its ligand-deceleration effect, in water turned into the ligand-accelerated process. By using this aqueous protocol, a range of allylic alcohols were epoxidized with up to 94% ee.

Polymer-supported organocatalysts: asymmetric reduction of imines with trichlorosilane catalyzed by an amino acid-derived formamide anchored to a polymer.

Asymmetric reduction of ketimines 1a-e with trichlorosilane can be catalyzed by the N-methylvaline-derived Lewis basic formamide anchored to a polymeric support (5a and 5b) with good enantioselectivity (< or =82% ee) and low catalyst loading (typically 15 mol %) at room temperature. This protocol represents a considerable simplification of the isolation procedure and is particularly suitable for a parallel synthesis of chiral amines 2a-e. The polymer-supported catalysts retain full activity after a multiple use.