The Direct catalytic asymmetric cross-Mannich reaction: a highly enantioselective route to 3-amino alcohols and alpha-amino acid derivatives

The first proline-catalyzed direct catalytic asymmetric one-pot, three-component cross-Mannich reaction has been developed. The highly chemoselective reactions between two different unmodified aldehydes and one aromatic amine are new routes to 3-amino aldehydes with dr>19:1 and up to >99 % ee. The asymmetric cross-Mannich reactions are highly syn-selective and in several cases the two new carbon centers are formed with absolute stereocontrol. The reaction does not display nonlinear effects and therefore only one proline molecule is involved in the transition state. The reaction was also catalyzed with good selectivity by other proline derivatives. The Mannich products were converted into 3-amino alcohols and 2-aminobutane-1,4-diols with up to >99 % ee. The first one-pot, three-component, direct catalytic asymmetric cross-Mannich reactions between unmodified aldehydes, p-anisidine, and ethyl glyoxylate have been developed. The novel cross-Mannich reaction furnishes either enantiomer of unnatural alpha-amino acid derivatives in high yield and up to >99 % ee. The one-pot, three-component, direct catalytic asymmetric reactions were readily scaled up, operationally simple, and conductible in environmentally benign and wet solvents. The mechanism and stereochemistry of the proline-catalyzed, one-pot, three-component, asymmetric cross-Mannich reaction are also discussed.     

Preparations of N- and P-substituted acetylenes under metal-free conditions

An efficient strategy towards triazole- or phosphine-oxide-substituted alkynes with the assistance of strong base LiHMDS is described. The facile and practical reaction took place from easily prepared substrates in a one-pot manner without participation of any transition metal catalysts or ligands, exhibiting good functional groups tolerance (up to 37 examples) and high efficiency (up to 90% yields). The isolation of the key intermediate proved the hypothesis of the proposed mechanism of the one-pot preparation.     

Organocatalytic Michael-Knoevenagel-hetero-Diels-Alder reactions: an efficient asymmetric one-pot strategy to isochromene pyrimidinedione derivatives

Synthesis of isochromene pyrimidinedione derivatives having five stereocenters has been achieved by a one-pot Michael-Knoevenagel condensation-inverse-electron-demand hetero-Diels-Alder reaction of α, β-unsaturated aldehydes, olefinic nitroalkanes, and 1,3-dimethylbarbituric acid via a one-pot strategy with excellent diastereo- and enantioselectivities (up to 99% ee). The structures and absolute configurations of the products were confirmed by X-ray analysis.     

A catalytic deracemisation of alcohols

Racemic alcohols have been converted into enantiomerically enriched alcohols with up to 99% ee in a one-pot oxidation/reduction procedure.     

Mechanochemical Synthesis of Short DNA Fragments

We demonstrate the first mechanochemical synthesis of DNA fragments by ball milling, enabling the synthesis of oligomers of controllable sequence and length using multi-step, one-pot reactions, without bulk solvent or the need to isolate intermediates. Mechanochemistry allowed for coupling of phosphoramidite monomers to the 5′-hydroxyl group of nucleosides, iodine/water oxidation of the resulting phosphite triester linkage, and removal of the 5′-dimethoxytrityl (DMTr) protecting group in situ in good yields (up to 60 % over three steps) to produce DNA dimers in a one-pot manner. H-Phosphonate chemistry under milling conditions enabled coupling and protection of the H-phosphonate linkage, as well as removal of the 5′-DMTr protecting group in situ, enabling a one-pot process with good yields (up to 65 % over three steps, or ca. 87 % per step). Sulfurization of the internucleotide linkage was possible using elemental sulfur (S8) or sulfur transfer reagents, yielding the target DNA phosphorothioate dimers in good yield (up to 80 % over two steps). This work opens the door to creation of solvent-free synthesis methodologies for DNA and RNA therapeutics.     

Synthesis of cycloparaphenylene under spatial nanoconfinement

Suzuki coupling reactions between symmetrical monomers were conducted in various mesoporous silica nanoreactors grafted with palladium catalysts, enabling the selective formation of [12]cycloparaphenylene precursor with separate yield up to 25% in one-pot reactions, much higher than that in homogeneous reaction. The spatial nanoconfinement of the nanoreactors promotes the macrocyclization while limits the concomitant linear oligomer formation, offering more possibilities for the synthesis of macrocycles from symmetrical monomers in one-pot reaction.     

In situ generation of 3,3,3-trifluoropropanal and its use for carbon-carbon bond-forming reactions

The DIBAL reduction of 2-phenylethyl 3,3,3-trifluoro-2-methylpropionate 2 at -78 degrees C afforded the aluminum acetal 3, and this intermediate, on worming up to 0 degrees C, was found to slowly decompose into the corresponding aldehyde 4, which smoothly reacted with appropriate nucleophiles in a one-pot manner in good to excellent yields with up to 93% diastereoselectivity.     

A consecutive one-pot two-step approach to novel trifluoromethyl-substituted bis(indolyl)methane derivatives promoted by Sc(OTf)3 and p-TSA

A one-pot two-step reaction of 3-(trifluoroacetyl)coumarin and indole afforded trifluoromethyl-substituted bis(indolyl)methane compounds containing coumarin skeleton. The atomic economic and simply manipulative reaction involved premier treatment of reaction mixtures with Sc(OTf)₃, followed by p-TSA in one-pot process. The reaction proceeded to give the title compounds in high yields (up to 95% yield).     

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%).     

微波辅助铜合成2-(N,N-二甲氨基)苯并噁唑衍生物

建立了一种简单实用、经济高效的以取代2-碘芳胺和N,N-二甲基氨基硫代甲酰氯为原料,以碘化亚铜为催化剂,吡啶为溶剂,100 ℃条件下,串联合成2-(N,N-二甲氨基)苯并噁唑衍生物的微波催化体系,合成了一系列中等至良好产率的2-(N,N-二甲氨基)苯并噁唑衍生物,最高产率达90%。     

三烯胺催化2,5-二烯酮的远端不对称Mannich反应

利用三烯胺机制活化环状2,5-二烯酮,对远端的不对称Mannich反应进行研究。用手性伯胺催化环状2,5-二烯酮原位生成三烯胺中间体,与苯甲醛和苯胺经三组分一锅法反应获得了7个新型的远端不对称Mannich加成产物,其结构经¹H NMR, ¹³C NMR和HR-MS(ESI)表征。在最佳反应条件下,收率达87%,对映选择性达78%。     

Diastereo- and enantioselective synthesis of oxazine and oxazolidine derivatives with a chiral quaternary carbon center under multifunctional catalysis

An easy one-pot, multistep cascade reaction which could afford a series of substituted benzo[d]pyrido[2,1-b]oxazolidine and [1,3]oxazine derivatives in a highly enantio- (up to 98% ee) and diastereoselective (4:1 to >20:1 dr) manner with generally good to excellent yields (up to 99%) has been developed. This well designed strategy could be applied to a wide scope of substrates under mild conditions with simple operations.     

Convenient, Efficient One-Pot Synthesis of Ferrocenylcyanide

In asymmetric catalysis, chiral (central chiral, planar chiral, axial chiral) ferrocenylligands is one of the most successful class of auxiliaries in recent years, and some ofthem have reached the stage of industrial applications'. But many challenges remain forthe synthesis of the intermediate. One of them is how to get ferrocenylcyanide I directlyfrom ferrocenecarboxyaldehyde 2, which can be easily prepared according to thecorresponding literature2. As far as known, I is an important interm…     

2-Phenallyl as a versatile protecting group for the asymmetric one-pot three-component synthesis of propargylamines

2-Phenallyl was found to be a versatile protecting group of primary amines for the asymmetric one-pot three-component synthesis of propargylamines which leads to enantiomeric excess of up to 96%; it can be easily removed with a palladium(0)-catalyzed allylic substitution using 1,3-dimethylbarbituric acid as a nucleophile.     

Copper-catalyzed synthesis of enantioenriched tetraarylethanes

Herein we report the asymmetric synthesis of 1,2-dipyridyl-1,2-diarylethanes via an unusual Cu(I)-catalyzed dimerization reaction. Subjection of a variety of enantioenriched substituted 2-pyridyl alcohols to a one-pot protocol generates the desired products in good yields and diastereoselectivities and with ee's up to >99%.     

Enantioselective one-pot three-component synthesis of propargylamines

[reaction: see text] A copper(I) complex of i-Pr-pybox-diPh has been found to be an efficient catalyst for an enantioselective one-pot three-component synthesis of propargylamines from aldehydes, amines, and alkynes. The reaction has been applied to a wide variety of aromatic aldehydes with excellent yields (up to 99%) and enantiomeric excesses (up to 99% ee). A transition-state model has been proposed to explain the stereochemical outcome of the reaction.     

Microwave-assisted one-pot synthesis of isoquinolines, furopyridines, and thienopyridines by palladium-catalyzed sequential coupling-imination-annulation of 2-bromoarylaldehydes with terminal acetylenes and ammonium acetate

A palladium-catalyzed microwave-assisted one-pot reaction for the synthesis of isoquinolines is developed. The reaction is carried out by sequential coupling-imination-annulation reactions of ortho-bromoarylaldehydes and terminal alkynes with ammonium acetate, and a variety of substituted isoquinolines, furopyridines, and thienopyridines is prepared in moderate to excellent yields (up to 86%).     

Enantioselective synthesis of beta-hydroxy acid derivatives via a one-pot aldol reaction-dynamic kinetic resolution

[reaction: see text]. Combining dynamic kinetic resolution with an aldol reaction provides access to beta-hydroxy ester derivatives with high enantiomeric purity (up to 99% ee) in a one-pot procedure. Only simple starting materials are required in this enantioselective process, and preformation of a silyl enol ether is not necessary.     

Asymmetric cyclizations via a sequential Michael addition/Conia-ene reaction by combining multifunctional quaternary phosphonium salt and silver catalysis

A one-pot asymmetric Michael addition/Conia-ene reaction sequence, catalyzed by combination of a dipeptide-derived multifunctional quaternary phosphonium salt and Ag₂CO₃ has been developed, which provides a series of synthetically important chiral methylenecyclopentane derivatives in moderate to excellent yields (up to 97%) and enantioselectivities (up to 93%).     

Highly diastereoselective synthesis of tetrahydropyridines by a C-H activation-cyclization-reduction cascade

A versatile reaction cascade leading to highly substituted 1,2,3,6-tetrahydropyridines has been developed. It comprises rhodium(I)-catalyzed C-H activation-alkyne coupling followed by electrocyclization and subsequent acid/borohydride-promoted reduction. This one-pot procedure affords the target compounds in up to 95% yield with >95% diastereomeric purity.