A new asymmetric organocatalytic nitrocyclopropanation reaction

Using 5-(pyrrolidin-2-yl)-1H-tetrazole as an organic catalyst, the nitrocyclopropanation of 2-cyclohexen-1-one has been achieved, proceeding in high yield and with good enantioselective control.     

Thermal effects in the organocatalytic asymmetric Mannich reaction

The proline-catalyzed direct asymmetric Mannich reaction between cyclohexanone, formaldehyde, and various anilines is thermally accelerated. With only 0.5 mol % of catalyst, Mannich products with up to 98% ee have been obtained after a short period of time in reactions performed under microwave irradiation. In situ reduction of the resulting ketones affords N-aryl amino alcohols in up to 86% yield.     

The direct organocatalytic asymmetric mannich reaction: unmodified aldehydes as nucleophiles

The unprecedented application of unmodified aldehydes as nucleophilic donors in direct catalytic asymmetric Mannich-type reactions is disclosed in a full account. Our efforts in broadening the applicability of chiral pyrrolidine-based catalysts in direct asymmetric Mannich-type reactions led to the highly diastereo- and enantioselective and concise synthesis of functionalized alpha- and beta-amino acids, beta-lactams, and amino alcohols.     

Bioinspired organocatalytic asymmetric reactions

Several small organic molecule catalysts are reminiscent of natural enzymes in their mode of action and substrate interaction/activation. This striking similarity has been a great source of inspiration for the development of new organocatalytic asymmetric processes. A few representative examples, mostly dealing with catalysts interacting through multiple hydrogen-bonds (synthetic oxyanion holes), are highlighted in this perspective.     

Aminohydroxyacetone synthons: versatile intermediates for the organocatalytic asymmetric aldol reaction

A practical method for the synthesis of 1,3-aminohydroxyacetone synthons was developed, and their utility in the organocatalytic asymmetric aldol reaction was demonstrated in a short synthesis of aza-sugars.     

A highly efficient asymmetric organocatalytic aldol reaction in a ball mill

Anti-aldol products with up to >99 % enantiomeric excess (ee) have been obtained by proline catalysis in excellent yields under experimentally simple solvent-free conditions. Efficient mixing of all the components is accomplished by applying a mechanochemical technique (ball milling). The catalysis is air and moisture tolerant and can be performed with non-purified starting materials. Even mixtures of solely solid compounds react, giving (mostly solid) products through a partially homogeneous (honey-like) intermediate melt. Since the reactant ratio is almost 1:1 (avoiding the common excess of ketone), the product isolation is easy leading to high aldol product yields.     

A one-pot asymmetric organocatalytic tandem reaction for the synthesis of oxazine derivatives

An easy one-pot tandem reaction catalyzed by a chiral secondary amine for the synthesis of optically active oxazine derivatives has been performed and the corresponding substituted benzo[d]pyrido[2,1-b][1,3]oxazine derivatives were afforded in generally high yields (up to 99%) and excellent enantioselectivities (up to >99%).     

Direct organocatalytic asymmetric alpha-chlorination of aldehydes

The direct organocatalytic enantioselective alpha-chlorination of aldehydes has been developed. The reaction proceeds for a series of different aldehydes with NCS as the chlorine source using easily available catalysts such as l-proline amide and (2R,5R)-diphenylpyrrolidine. The alpha-chloro aldehydes are obtained in up to 99% yield and up to 95% ee. The synthetic utility of the enantioselective alpha-chlorination of aldehydes is demonstrated by transformation of the alpha-chloro aldehydes to the corresponding alpha-chloro alcohols (>90% yield) by standard reduction and further transformation to both a terminal epoxide and amino alcohol, both obtained without loss of optical purity. Oxidation of the alpha-chloro aldehydes followed by esterification gave optically active alpha-chloro esters without loss of optical purity. It is demonstrated that these optically active alpha-chloro esters can be converted into nonproteinogenic amino acids in overall high yields, maintaining the enantiomeric excess obtained in the catalytic enantioselective alpha-chlorination step.     

Direct organocatalytic asymmetric reductive Mannich-type reactions

A direct asymmetric reductive Manich-type reaction that allows for the formation of three contiguous stereocenters with high chemo-, diastereo-, and enantioselectivity is presented.     

Regiospecific organocatalytic asymmetric aldol reaction of methyl ketones and alpha,beta-unsaturated trifluoromethyl ketones

[structure: see text]. The aldol reaction of methyl ketones and alpha,beta-unsaturated trifluoromethyl ketones occurred under mild conditions with the combination of proline-derived N-sulfonylamide and trifluoroacetic acid as the catalyst to give the corresponding unsaturated alpha-trifluoromethyl tertiary alcohols in high yields with good enatioselectivities.     

A one-pot organocatalytic asymmetric entry to tetrahydrothioxanthenones

A simple catalytic asymmetric synthesis of tetrahydrothioxanthenones is presented. The organocatalytic enantioselective domino reactions between 2-mercaptobenzaldehyde and α,β-unsaturated cyclic ketones proceed with excellent chemoselectivity to give the corresponding tetrahydrothioxanthenones in high yields and moderate to good enantioselectivities.     

Highly enantioselective organocatalytic Biginelli reaction

A series of binol- and H8-binol-based phosphoric acids have for the first time been evaluated for their ability to catalyze Biginelli reactions of aldehydes, thiourea or urea, and beta-keto esters. A new chiral phosphoric acid, derived from 3,3'-diphenyl-H8-binol, exhibited superior catalytic activity and enantioselectivity compared to its structural analogues, affording high enantioselectivities ranging from 85 to 97% ee with a wide scope of substrates. A metal-free preparation of optically active monastrol was achieved on the basis of the current process.