High Diasteroselectivity Research Articles

Dinuclear Zinc-AzePhenol Catalyzed Asymmetric Aza-Henry Reaction of N-Boc Imines and Nitroalkanes under Ambient Conditions

The asymmetric aza-Henry reaction of N-Boc imines and nitroalkanes was realized in the presence of 10 mol % dinuclear zinc-AzePhenol catalysts under ambient conditions. A variety of nitroamines were obtained in good yields (up to 97%) with excellent enantioselectivities (up to 99% ee) and high diasteroselectivity (up to 14:1 dr). Our protocol combined the operational simplicity and mild reaction conditions, thus making the process amenable for technical applications.

Experimental and Computational Studies on Remote γ-C(sp3)–H Silylation and Germanylation of Aliphatic Carboxamides

A Pd(II)-catalyzed protocol for highly regioselective distal γ-C–H silylation and germanylation of aliphatic carboxylic acids is reported. Bidentate 8-aminoquinoline as the directing group was found to stabilize the six-membered palladacycle. A variety of aliphatic carboxylic acids and amino acids were silylated and germanylated in good yields and high diasteroselectivities. Detailed mechanistic studies involving isolation of a Pd(II) intermediate, determination of the reaction rate and order, control experiments, and isotopic labeling and DFT studies were found to be crucial for elucidating the elementary steps involved in this distal aliphatic functionalization.

ChemInform Abstract: Synthesis of Chiral Piperazinones Using Amphoteric Aziridine Aldehyde Dimers and Functionalized Isocyanides.

We have evaluated a range of functionalized isocyanides in the aziridine aldehyde-driven multicomponent synthesis of piperazinones. High diasteroselectivity for each isocyanide was observed. A theoretical evaluation of the reaction course corroborates the experimental data. Moreover, the reactivity of cis- and trans-configured aziridine aldehyde dimers has been compared. This study further probes the dimer-driven mechanism of cyclization and enables an efficient access to a wide range of chiral piperazinones bearing functionalized side chains.

Photochemistry and Redox Chemistry of an Unsymmetrical Bimetallic Copper(I) Complex.

The bimetallic copper(I) complex Cu2L2 (cis-1) is formed with high diasteroselectivity from [Cu(NCCH3)4][BF4] and HL (4-tert-butyl phenyl(pyrrolato-2-yl-methylene)amine) in a kinetically controlled reaction. cis-1 features a rather short Cu···Cu distance of 2.4756(6) Å and is weakly emissive at room temperature in solution. Oxidatively triggered disproportionation of cis-1 yields elemental copper and the mononuclear copper(II) complex CuL2 (trans-2). One-electron reduction of trans-2 gives cuprate [2]- with a bent bis(pyrrolato) coordinated copper(I) entity. The imine donor atoms of [2]- can insert an additional copper(I) ion giving exclusively the bimetallic complex cis-1 closing the oxidation-elimination-reduction-insertion cycle.

Synthesis of Chiral Piperazinones Using Amphoteric Aziridine Aldehyde Dimers and Functionalized Isocyanides.

We have evaluated a range of functionalized isocyanides in the aziridine aldehyde-driven multicomponent synthesis of piperazinones. High diasteroselectivity for each isocyanide was observed. A theoretical evaluation of the reaction course corroborates the experimental data. Moreover, the reactivity of cis- and trans-configured aziridine aldehyde dimers has been compared. This study further probes the dimer-driven mechanism of cyclization and enables an efficient access to a wide range of chiral piperazinones bearing functionalized side chains.

Model Studies on Peroxidic Glutathione Transferase (GST) Inhibitors: C5‐Methylated 1,2,4‐Trioxanes with C6‐Acrylate Side Chains

AbstractThe 1,2‐hydroxy hydroperoxide 7 was obtained with high threo diastereoselectivity from the ester‐conjugated allylic alcohol 6 through a porphyrin‐sensitized singlet oxygen ene reaction. Compound 7 was used as substrate for peroxy(trans)acetalization with aldehydes, orthoesters, and acetals, catalyzed by boron and indium Lewis acids, as well as by PPTS as a Brønsted acid catalyst (for trioxane 10). The 1,2,4‐trioxane 8 was formed with high diasteroselectivity with all‐equatorially positioned substitutents at C‐3, C‐5, and C‐6. Additionally, perorthoester 9 was obtained by indium(III)‐catalyzed condensation of an orthoester with the hydroperoxide 7. The new compounds 8 and 9 exhibited moderate inhibition of human placental glutathione transferase (GST), comparable to that shown by the 5‐unsubstituted model trioxane 11.

Iridium-Catalyzed C–H Borylation of Cyclopropanes

The borylation of cyclopropanes catalyzed by the combination of (η(6)-mes)IrBpin3 or [Ir(COD)OMe]2 and a phenanthroline derivative is reported. The borylation occurs selectively at the methylene C-H bonds of the cyclopropane ring over methine or methyl C-H bonds. High diasteroselectivities were observed from reactions catalyzed by the combination of iridium and 2,9-Me2phenanthroline. The cyclopropylboronate esters that are generated are versatile synthetic intermediates that can be converted to trifluoroborate salts, boronic acids, cyclopropylarenes, cyclopropylamines, and cyclopropanols.

Electrocyclization of Oxatrienes in the Construction of Structurally Complex Pyranopyridones

Application of a tandem Knoevenagel/6π-electrocyclization sequence is able to produce highly substituted pyranopyridones from moderate to high yields in a one-step reaction. High diasteroselectivity is observed in some cases and was rationalized on the basis of the thermodynamic control of the evidenced reversibility of a 6π-electrocyclization reaction. Numerous examples are provided establishing a novel entry in natural product-like structures of pyranopyridone alkaloids.

Organocatalytic Michael Addition of Nitro Esters to α,β‐Unsaturated Aldehydes: Towards the Enantioselective Synthesis of trans‐3‐Substituted Proline Derivatives

AbstractA facile five‐step strategy has been developed for the enantioselective synthesis of trans‐3‐substituted proline derivatives with high diasteroselectivity (dr>20:1) and enantioselectivity (up to 97% ee). The key step is the asymmetric organocatalytic Michael addition of nitro esters to α,β‐unsaturated aldehydes, which affords the chiral Michael adducts in high yields (up to 96%) and excellent enantioselectivity (up to 99% ee) by using diarylprolinol silyl ether as the organocatalyst.

Combined Theoretical and Experimental Study on High Diastereoselective Chirality Transfer Based on [2.2]Paracyclophane Derivative Chiral Reagent

We report a paracyclophane N-Me thioamide chiral reagent for the asymmetric thio-Claisen rearrangement with high diasteroselectivity. Comparisons between candidate chiral reagent N-phenyl-N-([2.2]paracyclophan-4-yl)amide, N-methyl amide, N-phenyl thioamide, and N-methyl thioamide are made both by experiment and theoretical calculations to clarify the principle behind the high diasteroselectivity. Dynamic (1)H NMR phenomenon tested by varying temperature (VT) experiments has proved that N-Ph amides have triple splitting peaks, while N-Ph thioamide would reduce the number to two, further substituting the Ph to Me made dynamic phenomenon disappear. So the side chain is thought to be the most rigid in N-Me thioamide, which accounts for a structure prerequisite favoring high efficient chirality transfer. This is confirmed by theoretical calculation: remarkable energy difference exists between the Re and Si faces of the chiral molecule. To further clarify the possible pathways for thio-Claisen rearrangement, theoretical prediction is adopted. The result implies that the cisoid pathways will dominate the process. Further experiment confirmed this: with N-Me thioamide, the asymmetrical reaction affords γ-unsaturated thioamides in good yields and high diastereoselectivities up to 98%. After removing the thioamide auxiliaries under hydrolysis conditions, product β,γ-substituted chiral alcohols reached high enantiopurity of 98% ee.

Carbons supported bio-ionic liquids: Stability and catalytic activity

[Chol][Pro] was supported on different porous carbon materials. Subsequently, the catalytic activity of the heterogeneous systems in the Michael reaction between cyclohexanone and β-nitrostyrene was studied. Excellent conversions and high diasteroselectivities were attained by supporting [Chol][Pro] on the heat treated mesoporous carbons. The stability of the [Chol][Pro] and consequently, its catalytic activity were strongly influenced by the textural and surface chemical properties of the carbon supports.

Synthesis, characterization and X-ray studies of new chiral five-six-membered ring, [4.3.0] heterobicyclic system of monomeric boronates

Nine new boronates, six of them chiral, with five-six-membered ring heterobicycles were prepared by reaction of the Schiff bases and phenyl boronic acid. The boronates were fully characterized by spectroscopic techniques, NMR 1H, 13C, 11B, Infrared spectroscopy, mass spectrometry and elemental analysis. The reaction showed high diasteroselectivity, only in the case of compound 4c, containing a methyl substituent in the aliphatic moiety, the induction is low giving a 2:1 mixture of two diatereoisomers. The results showed that the preferred stereochemistry in the heterocycles is that where all substituents in the five membered ring and the phenyl group attached to boron atom are on the same side.

Highly enantioselective synthesis of anti aryl β-hydroxy α-amino esters via DKR transfer hydrogenation

An efficient preparation of highly enantiomerically enriched aryl β-hydroxy α-amino esters via dynamic kinetic resolution (DKR), asymmetric transfer hydrogenation of α-amino β-keto esters is described. The anti β-hydroxyl α-amino esters were obtained both in high yields and high diasteroselectivity. The observed high anti selectivity is inconsistent with the previous results in literature. The absolute stereochemistry of the aryl β-hydroxy α-amino esters was unambiguously confirmed via chemical derivatization as well as Vibrational Circular Dichroism (VCD) techniques.

Diversity Oriented Synthesis of Pyrrolidines via Natural Carbohydrate Solid Acid Catalyst

Natural carbohydrate scaffold catalyzed diastereoselective synthesis of functionalized pyrrolidines have been developed via 1,3-dipolar cycloaddition of azomethine ylides derived from alpha-imino esters with dienes or dipolarophiles. Naturally most abundant carbohydrates, like cellulose and starch, were converted into their sulfuric acid derivative, which are exhibiting efficient catalytic properties, along with excellent cost effectivity and recyclability. The advantages of this methodology are diversity oriented metal free synthesis of functionalized pyrrolidines, mild reaction condition, high diasteroselectivity and yield.

Eco‐Friendly Olefin Dihydroxylation Catalyzed by Diphenyl Diselenide

AbstractThe first general and efficient diphenyl diselenide‐catalyzed dihydroxylation of double bonds is presented. Hydrogen peroxide can be used as the oxidizing agent, affording generally good yields and high diasteroselectivity.

An Efficient Total Synthesis of (.+‐.)‐Lycoramine

A short and unique approach to (±)-lycoramine as one of the galanthamine-type alkaloids has been efficiently developed. The alternative advantage lies in that three stereocenters, including a crucial quaternary carbon center, were constructed with high diasteroselectivity via a key one-step NBS-mediated semipinacol rearrangement of the allylic alcohol.

An Efficient Total Synthesis of (±)-Lycoramine

[reaction: see text] A short and unique approach to (+/-)-lycoramine as one of the galanthamine-type alkaloids has been efficiently developed. The alternative advantage lies in that three stereocenters, including a crucial quaternary carbon center, were constructed with high diasteroselectivity via a key one-step NBS-mediated semipinacol rearrangement of the allylic alcohol.

Nitroalkylation and nitroalkenylation reactions of γ-lactone enolates. A facile ring switch from polysubstituted γ-lactones to polysubstituted γ-lactams

Michael addition of lithium enolates of γ-butyrolactone 1 and α-methyl-γ-butyrolactone 1′ to ( E)-1-nitropropene 2 , ( E)-β-nitrostyrene 3 and ( E)-2-nitro-1-phenylpropene 4 is described. Reactions of the lithium enolate of 1′ with 2 and 4 occurred with high diasteroselectivity (80 and 92% d.e., respectively). Reactions of the zinc enolate of 1′ with two β-nitroenamines and two methylthio-substituted 1-amino-2-nitro-1,3-dienes were also examined. Catalytic reduction of the nitroalkylated and nitroalkenylated products allowed the achievement of functionalized γ-lactams and/or cyclic hydroxamic acids.

Meldrum’s Acid

Meldrum"s acid (1, isopropylidene malonate or 2,2-di­methyl-4,6-dioxo-1,3-dioxane), was first synthesized by Meldrum in 1908 [1] and the structure was incorrectly assigned as the b-lactone of b-hydroxyisopropylmalonic acid (b,b-dimethyl-b-propiolactone-a-carboxylic acid). [2] It was only 40 years later that Davidson and Bernhard assigned the correct structure. [2] Meldrum’s acid has attracted considerable attention due to its high acidity (pK a = 4.97) [3] and rigid cyclic structure. Acylated derivatives (synthetic equivalents of mixed ketenes) readily undergo alcoholysis to give b-keto esters. [4] Alkylidene derivatives are strong electrophiles and can undergo Diels-Alder reactions with high diasteroselectivity. [5] This versatile tool is a key intermediate for a large number of important building blocks and there remains much to discover.

Diastereoselective formation of anellated tetrahydrofurans using a nitrate radical induced oxidative, self-terminating radical cyclization cascade

Addition of electrogenerated nitrate radicals to CC triple bonds in the alkynyl ethers cis- 7–9 and trans- 8–9 yields anellated tetrahydrofurans 12–16 with high diasteroselectivity through a new type of an oxidative, self-terminating radical cyclization cascade. The reaction probably proceeds via an intramolecular, rate-determining hydrogen atom transfer in the vinyl radical of type 17a, and a subsequent diastereoselective 5- exo radical cyclization. Elimination of nitrogen dioxide terminates the reaction sequence. This reaction is a remarkable example for the creation of a CO bond by intermolecular addition of an O-centered radical to a π-system.