Recent advances in asymmetric reactions catalyzed by chiral phosphoric acids

This review summarizes the very recent advances in asymmetric reactions catalyzed by chiral phosphoric acids（CPAs）, a family of versatile catalysts that catalyze a broad range of reactions to afford diverse chiral molecules. In the past years, different kinds of chiral phosphoric acids have been designed and developed into a privileged class of catalysts in asymmetric synthesis. A number of remarkable achievements have been made by many groups around the world. Due to length limitation, this review only summarizes those works published from January 2016 to November 2017. Meanwhile, catalytic systems which combine metal catalysts and chiral phosphoric acids will not be discussed in this review.

Asymmetric PCR method in generation of HBV ssDNA for pyrosequencing

Objective To explore the optimal primer ratio and concentration of asymmetric polymerase chain reaction (A-PCR) in producing hepatitis B virus (HBV) single-stranded DNA (ssDNA) for pyrosequencing. Methods A-PCR was carried out to generate HBV ssDNA with forward to reverse primers of different ratios (50∶1, 100∶1) and concentrations (13.0 pmol/25μL and 0.14 pmol/25μL, 19.5 pmol/25μL and 0.21 pmol/25μL), and the product yield and quality were compared respectively. Results The forward to reverse primer ratio of 50∶1 provided better yield and concentration of 19.5 pmol/25μL and 0.21 pmol//25μL generated a clearer band. Conclusion A simple and feasible method to produce HBV ssDNA for pyrosequencing in batch is established.

Asymmetric Reformatsky Reaction Induced by Dipeptides

For the first time, synthetic dipeptides were applied to the catalysis of asymmetric Reformatsky reaction. Review in this domain & factors influencing enantioselectivity were discussed.

Direct asymmetric aldol reaction using MBHA resin-supported peptide containing L-proline unit

MBHA resin-supported tripeptide catalyst system containing L-proline unit has been developed for use in the direct asymmetric aldol reaction of acetone and aldehydes, which afford the corresponding products with satisfactory isolated yields and enantiomeric excesses. 2009 Hong Bin Zou. Published by E]sevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Asymmetric Baylis-Hillman Reaction between Chiral Activated Alkenes and Aromatic Aldehydes in Me_(3)N/H_(2)O/Solvent Medium

Chiral activated alkene, L-menthyl acrylate and （＋）-N-α-phenylethyl acrylamide, induced asymmetric Baylis-HiUman reaction of aromatic aldehydes was realized at 25℃ for 7 days in Me3N/H2O/solvent homogeneous medium. The corresponding Baylis-Hillman adducts were obtained in good chemical yield with moderate to excellent diastereoselectivity （up to 99% de）.

Asymmetric Diels-Alder Reaction of 1-(S_R)-p-Tolylsulfinyl-3-penten-2-one with Cyclopentadiene Catalzed by a Chiral Titanium Reagent

Double asymmetric Diels-Alder reaction of 1(SR)-p-Tolylsulfinyl-3-penten-2-one with cyclopentadiene using a chiral titanium reagent was performed. The diastereoselectivity dependent on the size of aryl substituent involved in the chiral ligands was discussed Absolute configuration of the cycloadducts was conformed. Dramatic reversal of selectivity is observed.

ASYMMETRIC 1,3-DIPOLAR CYCLOADDITION REACTION BY A CHIRAL SOURCE,5-(1-MENTHYLOXY)-2(5-H)-FURANONE

5-(1-Menthyloxy)-2(5-H)-furanone is used as s chiral dipolarophile for thermal asymmetric 1,3-dipolar cycloaddition reaction with C-phenyl-N-phenyl nitrone to give the diastereomerically pure cycloaddition product.

Precise Detection,Control and Synthesis of Chiral Compounds at Single‑Molecule Resolution

Chirality,as the symmetric breaking of molecules,plays an essential role in physical,chemical and especially biological processes,which highlights the accurate distinction among heterochiralities as well as the precise preparation for homochirality.To this end,the well-designed structure-specific recognizer and catalysis reactor are necessitated,respectively.However,each kind of target molecules requires a custom-made chiral partner and the dynamic disorder of spatial-orientation distribution of molecules at the ensemble level leads to an inefficient protocol.In this perspective article,we developed a universal strategy capable of realizing the chirality detection and control by the external symmetry breaking based on the alignment of the molecular frame to external stimuli.Specifically,in combination with the discussion about the relationship among the chirality(molecule),spin(electron)and polarization(photon),i.e.,the three natural symmetry breaking,single-molecule junctions were proposed to achieve a single-molecule/event-resolved detection and synthesis.The fixation of the molecular orientation and the CMOS-compatibility provide an efficient interface to achieve the external input of symmetry breaking.This perspective is believed to offer more efficient applications in accurate chirality detection and precise asymmetric synthesis via the close collaboration of chemists,physicists,materials scientists,and engineers.

Tetrahydrobenzo[5]helicenediol derivatives as additives for efficient proline-catalyzed asymmetric List-Lerner-Barbas aldol reactions of bulky aldehyde substrates

Tetrahydrobenzo[5]helicenediol（THB-[5]HDIOL） derivatives as additives for the efficient prolinecatalyzed asymmetric List-Lerner-Barbas（LLB） aldol reactions of bulky aldehyde substrates was described. It was found that with dibromo-substituted helical diols P-4 a/M-4 a as additives, the prolinecatalyzed LLB aldol reaction of 9-anthraldehyde and acetone gave the product in 83% yield and 99% ee.Transition state models revealed an edge-to-face p-p stacking between the anthracenyl group in TS（R）and the phenyl group of the additive, which might result in the high enantioselectivity.

A rapid and sensitive method to detect mycobacterium tuberculosis DNA by fluorescence polarization

Objective: To develop a new high sensitivity, rapid and simple mycobacterium tuberculosis DNA detection method using fluorescence polarization technology. Methods: In our asymmetric PCR protocol, 100 times mole of TB-R primer was added than in the usual symmetric PCR to get enough single strands PCR product. The probe TB-5′-TAMRA and PCR products were mixed in a tube and incubate for 5-15 min at 46 ℃.The polarization (mp) was measured using victor2 Multilabel Plate Reader. Results: Asymmetric and symmetric PCR products were analyzed by the FP method. Asymmetric PCR products are detected more sensitively than symmetric ones. The polarization values of probe associated with asymmetric products were much higher than with symmetric products. Conclusion: This fluorescence polarization assay in conjunction with asymmetric PCR is a powerful and widely applicable method for the rapid and sensitive detection of micro-organisms in clinical laboratories.

One-pot-synthesis of novel cinchonine-based phosphites

Cinchonine was employed as backbone for the synthesis of novel phosphite compounds with diol substituents. These monophosphinites were provided in one pot with the yields ranged from 63% to 75%. Their structures were confirmed by NMR spectroscopy and HRMS. C 2009 Sheng Yong Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Catalytic Asymmetric Carbon-Carbon Forming Reactions Catalyzed Chiral Schiff Base-Metal Complexes

1 Results In 1991, we disclosed the novel asymmetric catalysts prepared from chiral Schiff base and titanium alkoxide in the reaction of asymmetric silylcyanation of aldehydes (eq.1)[1]. Since our first report, chiral Schiff base-metal complex was proven to be efficient in a variety of asymmetric reactions. We reported the first example of enantioselective addition of diketene to aldehydes promoted by chiral Schiff base-titanium alkoxide complexes (eq.2)[2]. The products of this reaction have been cove...

Synthesis and Crystal Structure of Spiro[1-bromo-4-l-menthyloxy-5-oxo-6-oxa-bicyclo[3.1.0]hexane-2,2'-3'-(16''-methoxyacetatyl-4'-l-menthyloxybutyrolactone)]

The title compound, spiro[ 1-bromo-4-l-menthyloxy-5-oxo-6-oxa-bicyclo[3.1.0]- hexane-2,2＇-3＇-（16＇-methoxyacetatyl-4＇-l-menthyloxybutyrolactone）] 1, was obtained via tandem asymmetric double Michael addition/internal nucleophilic substitution of the chiral synthon, 5-l-menthyloxy-3-bromo-2-（5H）-furanone 2 with methoxy α-chloroacetate as a nucleophile under mild conditions, and structurally [letermined by single-crystal X-ray diffraction. Crystal data： C31H47BrO9, Mr = 643.60, orthorhombic, space group P212121. α = 9.6564（7）, b = 14.8994（11）, c = 23.6771（17） A, V= 3406.5（4） A^3, Z = 4, Dc= 1.255 g/cm^3, 2（MoKa） = 0.71073 A,μ= 1.254 mm^-1 and F（000） = 1360. The structure was refined to R =[0.0324 and wR = 0.0737 for 5123 observed reflections （I〉 2σ（I））. The crystallographic results of molecule 1 show that the interesting reaction of 2 with methoxy α-chloroacetate, in the usual manner, gave the spiro-cyclopropane skeleton with O-linked derivative containing multiple stereogenic centers 1 rather than the expected C-linked derivative.

Synthesis and Crystal Structure of Spiro[1-bromo-4-methoxy-5-oxa-6-oxo-bicyclo[3.1.0]hexane-2,2＇-（3＇-cyclohexanoxy-4＇-methoxybutyrolactone）

The title compound, spiro[1-bromo-4-l-menthyloxy-5-oxo-6-oxa-bicyclo[3.1.0]-hexane-2,2-3-(16-methoxyacetatyl-4-l-menthyloxybutyrolactone)] 1, was obtained via tandem asymmetric double Michael addition/internal nucleophilic substitution of the chiral synthon, 5-l-menthyloxy-3-bromo-2-(5H)-furanone 2 with methoxy α-chloroacetate as a nucleophile under mild conditions, and structurally determined by single-crystal X-ray diffraction. Crystal data: C31H47BrO9, Mr = 643.60, orthorhombic, space group P212121, a = 9.6564(7), b = 14.8994(11), c = 23.6771(17) , V = 3406.5(4) 3, Z = 4, Dc = 1.255 g/cm3, λ(MoKα) = 0.71073 , μ = 1.254 mm-1 and F(000) = 1360. The structure was refined to R = 0.0324 and wR = 0.0737 for 5123 observed reflections (I > 2σ(I)). The crystallographic results of molecule 1 show that the interesting reaction of 2 with methoxy α-chloroacetate, in the usual manner, gave the spiro-cyclopropane skeleton with O-linked derivative containing multiple stereogenic centers 1 rather than the expected C-linked derivative.

Synthesis of chiral allylic phosphonates via asymmetric reductive cross-coupling of α-bromophosphonates and vinyl bromides

Chiral phosphine-containing skeletons play a pivotal role in bioactive natural products, pharmaceuticals, chiral catalysts, and ligands. Despite considerable progress has been made in the synthesis of chiral phosphorus compounds, the development of facile and modular methods to access chiral allylic phosphorus compounds remains challenging due to the simultaneous control required for reactivity, enantioselectivity, and stereoselectivity. Herein, we present a general and modular platform to achieve the asymmetric reductive cross-coupling of α-bromophosphonates and vinyl bromides, enabling the synthesis of highly valuable chiral allylic phosphonate products with remarkable yields, enantioselectivities, and stereoselectivities.

Catalytic Enantioselective Methanolysis of 4 -substituted-2-phenyl-5(4H)-oxazolones by Cinchonine

Cinchonine alkaloid catalyzed enantioselective methanolysis of six 4-substituted 2-phenyl-5(4H)-oxazolones to (S)-methyl N-benzoyl-alpha-amino acid esters with 10-33% e.e and 72-81% yield.

Who is Who in the Carbene Chemistry of N-Sulfonyl Hydrazones

Over the past few decades,N-sulfonyl hydrazones have been recognized as alternative precursors for hazardous diazo compounds in organic synthesis,allowing for diverse innovative and original chemical transformations that were otherwise difficult to achieve.This critical review summarizes the major advancements in the carbene chemistry of N-sulfonyl hydrazones.The contents of this review are organized based on research conducted by leading scientists who have made significant contributions to this field.The individual carbene transfer reactions and their mechanisms,as well as the potential applications in the synthesis of natural products and complex bioactive molecules,are thoroughly discussed.

Carbene-catalyzed activation of cyclopropylcarbaldehydes for mannich reaction andδ-lactam formation:remote enantioselecitvity control and dynamic kinetic asymmetric transformation

An N-heterocyclic carbene(NHC)-catalyzed enantioselective Mannich reaction of the remoteγ-carbon of cyclopropylcarbaldehydes is disclosed for the first time.Diastereo-and enantiomerically enriched multicyclicδ-lactam compound is afforded as the main product from 8 possible stereo-specific isomers through dynamic kinetic asymmetric transformation(DYKAT)processes.Multiple chiral functional molecules can be afforded from the lactam products through simple protocols with retentions of the optical purities.

A New Approach to the Asymmetric Reaction of the Chiron 5-L-Menthyloxy-2(5H)-furanones with Horner-Emmons Reagent

The asymmetric reaction of the chiron 2(5H)-furanones (4a-4c) with the Homer-Emmons reagents (5a-5b) has been investigated. The newly chiral organophosphorus derivatives 6 and 7 were obtained using the phosphoryl-stabilized carbanion as a building block in DMSO under mild conditions. Through the asymmetric introduction, the Horner-Emmons reagent could be transformed to a chiral building block to afford the novel functionalized phosphorus derivatives. The structures of the synthesized compounds 6 and 7 were identified on the basis of their elementary and spectroscopic data, such as IR, 1H NMR, 13C NMR, MS and X-ray crystallography. These results provided a valuable approach to the synthesis of potentially interesting chiral organophosphorus derivatives and probing their biological activities.