A high-yield, highly diastereo- and enantioselective nitro-Mannich reaction of α-aryl nitromethanes with amidosulfones catalyzed by a novel chiral phase-transfer catalyst, bearing multiple H-bonding donors, derived from quinine was developed. A variety of α-aryl nitromethanes and amidosulfones were investigated; and the corresponding products were obtained in excellent yields with excellent diastereo- and enantioselectivities (up to 99% yield, > 99:1 dr and >99% ee). As a demonstration of synthetic utility, the resulting β-nitroamines could be converted to corresponding meso-symmetric and optically pure unsymmetric anti-1,2-diarylethylenediamines.

New quaternary ammonium types of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors derived from α-amino acids were readily prepared and found to be highly efficient in the asymmetric nitro-Mannich reactions of amidosulfones. Very broad substrate generality was observed, and the products were achieved in high enantio-/diastereoselectivities (90–>99.9% ee, 90 : 10 to 92 : 8 dr). Compared with previous reports, the enantioselectivity of aliphatic amidosulfones has been improved to a high level (91–93% ee).

The enantioselective nitro-Mannich reaction of unactivated ketone-derived imines (ketimines) has long been a challenge. With the introduction of the protecting group 6-methyl-2-pyridylsulfonyl to the ketimines, this challenging reaction was performed successfully by using a novel bifunctional quaternary ammonium salt bearing a thiourea group derived from quinine, and when relatively small quantities of nitroalkanes were used, the corresponding products were obtained in good to high yields with high enantioselectivities (up to 93% ee). Density functional theory (DFT) calculations are also performed to give the possible transition-state model.

•Synthesized a series of APT catalysts bearing multiple H-bonding donors.•First (PTC) system used in this reaction.•Good reaction activity and enantioselectivities (yields 96–99%, up to 95% ee).A series of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors derived from cinchona alkaloids are synthesized, and successfully applied to asymmetric nitro-Mannich of isatin-derived N-Boc ketimines. The products 3-substituted 3-amino-oxindoles were constructed in excellent yields (96–99%) and good enantioselectivities (up to 95% ee).Download high-res image (94KB)Download full-size image

AbstractAn efficient diastereo- and enantioselective aza-Henry reaction of β,γ-unsaturated nitroalkenes with N-Boc amidosulfones has been realized under the catalysis of bifunctional chiral phase-transfer catalysts bearing multiple H-bonding donors, which was derived from cinchona alkaloids. This asymmetric catalytic protocol is suitable for a wide range of substrates, and give the corresponding products in high to excellent yields (up to 99%) with excellent diastereo- and enantioselectivities (up to >99 : 1 dr, up to >99% ee). Density functional theory (DFT) calculations are also performed and give the possible transition-state model to illustrate the mechanism of the developed reaction.

•A metal-free pathway for forming 6-aryl(alkyl)thiophenanthridines is developed.•This pathway is characterized by SH bond cleavage, then CS/CC bond formation.•This reaction is suitable for a wide scope of substrates.A metal-free pathway for constructing 6-aryl(alkyl)thiophenanthridines through oxidative cascade cyclization of isocyanides with thiols is developed. This pathway is characterized by SH bond cleavage of commercially available thiols, and subsequent CS/CC bond formation, which is suitable for a wide scope of substrates and by which a variety of 6-aryl(alkyl)thiophenanthridines could be synthesized in good to excellent yields.

We have developed a new base-promoted intermolecular cascade cyclization reaction of substituted 3-aryl(heteroaryl)-3-chloroacrylaldehydes and tetrahydroisoquinolines in one pot. The reaction provides a facile and practical synthesis of pyrrolo[2,1-a]isoquinolines. A number of pyrrolo[2,1-a]isoquinolines were synthesized in moderate to high yields (up to 97%).

Bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors have rarely been explored. The first quaternary ammonium type of these catalysts derived from cinchona alkaloids were readily prepared and found to be highly efficient catalysts for asymmetric nitro-Mannich reactions of amidosulfones. Compared with previous reports, very broad substrate generality was observed, and both enantiomers of the products were achieved in high enantio- and diastereoselectivity (90–99% ee, 13:1 to 99:1 dr).

Multi-component condensation of 2-naphthol, aromatic aldehydes, and cyclic 1,3-dicarbonyl compounds catalyzed by ionic liquid [NSPTEA][HSO4] was accomplished for the synthesis of a series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones under solvent-free conditions. High yields, ease recovery, short reaction time and reusability of catalyst are significant advantages. ZrOCl2·8H2O was also found to act as an effective catalyst towards this transformation.

The enantioselective nitro-Mannich reaction of unactivated ketone-derived imines (ketimines) has long been a challenge. With the introduction of the protecting group 6-methyl-2-pyridylsulfonyl to the ketimines, this challenging reaction was performed successfully by using a novel bifunctional quaternary ammonium salt bearing a thiourea group derived from quinine, and when relatively small quantities of nitroalkanes were used, the corresponding products were obtained in good to high yields with high enantioselectivities (up to 93% ee). Density functional theory (DFT) calculations are also performed to give the possible transition-state model.