Unprecedented Stereoselectivity Research Articles

A Catalytic Asymmetric Pictet–Spengler Platform as a Biomimetic Diversification Strategy toward Naturally Occurring Alkaloids

Tetrahydroisoquinoline (THIQ) alkaloids constitute a large and diverse class of bioactive natural products, with the parent compounds and related downstream biosynthetic secondary metabolites spanning thousands of isolated structures. Chemoenzymatic synthetic approaches toward the relevant THIQs rely on Pictet–Spenglerases such as norcoclaurine synthase (NCS), the scope of which is strictly limited to dopamine-related phenolic substrates. To overcome these limitations in the context of chemical synthesis, we herein report asymmetric Pictet–Spengler reactions of N-carbamoyl-β-arylethylamines with diverse aldehydes toward enantioenriched THIQs. The obtained products proved to be competent intermediates in the synthesis of THIQ, aporphine, tetrahydroberberine, morphinan, and androcymbine natural products. Novel catalyst design with regard to the stabilization of cationic intermediates was crucial to accomplish high reactivity while simultaneously achieving unprecedented stereoselectivity for the reaction of biologically relevant substrates.

Tethered Tungsten-Alkylidenes for the Synthesis of Cyclic Polynorbornene via Ring Expansion Metathesis: Unprecedented Stereoselectivity and Trapping of Key Catalytic Intermediates.

This report describes an approach for preparing tethered tungsten-imido alkylidene complexes featuring a tetra-anionic pincer ligand. Treating the tungsten alkylidyne [tBuOCO]W≡CtBu(THF)2 (1) with isocyanates (RNCO; R = tBu, Cy, and Ph) leads to cycloaddition occurring exclusively at the C═N bond to generate the tethered tungsten-imido alkylidenes (6-NR). Unanticipated intermediates reveal themselves, including the discovery of [(O2CtBuC═)W(η2-(N,C)-RNCO)(THF)] (11-R) and an unprecedented decarbonylation product [(tBuOCO)W(≡NR)(tBuCCO)] (14-R), on the pathway to the formation of 6-NR. Complex 11-R is kinetically stable for sterically bulky isocyanate R = tBu (11-tBu) and is isolated and characterized by single-crystal X-ray diffraction. Finally, adding to the short list of catalysts capable of ring expansion metathesis polymerization (REMP), complexes 6-NR and 11-tBu are active for the stereoselective synthesis of cyclic polynorbornene.

ChemInform Abstract: Palladium‐Catalyzed Intermolecular Dehydrogenative Aminohalogenation of Alkenes under Molecular Oxygen: An Approach to Brominated Enamines.

AbstractThe reaction proceeds with mostly excellent (Z)‐selectivity.

Palladium-Catalyzed Intermolecular Dehydrogenative Aminohalogenation of Alkenes under Molecular Oxygen: An Approach to Brominated Enamines

A novel and efficient palladium-catalyzed dehydrogenative aminohalogenation of alkenes with molecular oxygen as the sole oxidant has been developed. This protocol provides a valuable synthetic tool for the assembly of a wide range of brominated enamines under mild conditions, with unprecedented stereoselectivity and exceptional functional group tolerance. This attractive route for the synthesis of brominated enamines is of great significance due to the products' versatile reactivity for further transformations.

High 1,3-trans Stereoselectivity in Nucleophilic Substitution at the Anomeric Position and β-Fragmentation of the Primary Alkoxyl Radical in 3-Amino-3-deoxy-ribofuranose Derivatives: Application to the Synthesis of 2-epi-(−)-Jaspine B

The high inverse stereoselectivity in the nucleophilic substitution at the anomeric position of 3-amino-3-deoxy-ribofuranose derivatives is reported. This unprecedented stereoselectivity is explained in terms of preferential nucleophilic attack on the "inside face" of the respective five-membered ring oxocarbenium ion that orients pseudoequatorially to the benzylamine group placed at the C-3 position. In addition, an unusual β-fragmentation of a primary alkoxyl radical generated from its corresponding N-phthalimide derivative was achieved, and thus taking advantages of both reactions, the total synthesis of 2-epi-(-)-jaspine B was completed.

ChemInform Abstract: Stereochemical Control in the Metallohalocarbenoid Route to Linear Enediynes.

Abstract Methods for the stereoselective preparation and unmasking of disubstituted Z enediynes are reported. The origins of the unprecedented stereoselectivity of the process are uncovered.

A Bacterial Enzyme Catalyzing Double Reduction of a β,δ-Diketo Ester with Unprecedented Stereoselectivity

AbstractVarious ketoreductases exclusively participate in all common biological events, and they are a class of important biocatalysts for the production of chiral alcohols. While many types of ketoreductase have been extensively studied and their functions, properties and utilities have been well known, the capability of stereoselectively reducing two carbonyl groups in the same diketohexanoate ester molecule to form a dihydroxy product by a single ketoreductase has not been evidently characterized. Here we show that a unique and novel enzyme, diketoreductase, was cloned from Acinetobacter baylyi, heterogeneously expressed in Escherichia coli and purified to homogeneity. The diketoreductase is up to 78% homologous to bacterial 3-hydroxyacyl coenzyme-A reductases. However, recombinant diketoreductase does not reduce HMG-CoA, showing that the inference of function of enzymes like the diketoreductase based on sequence homology may be in error. The enzyme directly converts a β,δ-diketo ester to the corresponding dihydroxy ester. More remarkably, our results demonstrate that the recombinant enzyme possesses unprecedented stereoselectivity with both diastereomeric and enantiomeric excesses of greater than 99%. This new enzyme is of immediate value in developing a practical biocatalytic route to the side chains of statin drugs, such as Lipitor®.

A Bacterial Enzyme Catalyzing Double Reduction of a β,δ-Diketo Ester with Unprecedented Stereoselectivity

Various ketoreductases exclusively participate in all common biological events, and they are a class of important biocatalysts for the production of chiral alcohols. While many types of ketoreductase have been extensively studied and their functions, properties and utilities have been well known, the capability of stereoselectively reducing two carbonyl groups in the same diketohexanoate ester molecule to form a dihydroxy product by a single ketoreductase has not been evidently characterized. Here we show that a unique and novel enzyme, diketoreductase, was cloned from Acinetobacter baylyi, heterogeneously expressed in Escherichia coli and purified to homogeneity. The diketoreductase is up to 78% homologous to bacterial 3-hydroxyacyl coenzyme-A reductases. However, recombinant diketoreductase does not reduce HMG-CoA, showing that the inference of function of enzymes like the diketoreductase based on sequence homology may be in error. The enzyme directly converts a β,δ-diketo ester to the corresponding dihydroxy ester. More remarkably, our results demonstrate that the recombinant enzyme possesses unprecedented stereoselectivity with both diastereomeric and enantiomeric excesses of greater than 99%. This new enzyme is of immediate value in developing a practical biocatalytic route to the side chains of statin drugs, such as Lipitor®.

A Bacterial Enzyme Catalyzing Double Reduction of a β,δ-Diketo Ester with Unprecedented Stereoselectivity

AbstractVarious ketoreductases exclusively participate in all common biological events, and they are a class of important biocatalysts for the production of chiral alcohols. While many types of ketoreductase have been extensively studied and their functions, properties and utilities have been well known, the capability of stereoselectively reducing two carbonyl groups in the same diketohexanoate ester molecule to form a dihydroxy product by a single ketoreductase has not been evidently characterized. Here we show that a unique and novel enzyme, diketoreductase, was cloned from Acinetobacter baylyi, heterogeneously expressed in Escherichia coli and purified to homogeneity. The diketoreductase is up to 78% homologous to bacterial 3-hydroxyacyl coenzyme-A reductases. However, recombinant diketoreductase does not reduce HMG-CoA, showing that the inference of function of enzymes like the diketoreductase based on sequence homology may be in error. The enzyme directly converts a β,δ-diketo ester to the corresponding dihydroxy ester. More remarkably, our results demonstrate that the recombinant enzyme possesses unprecedented stereoselectivity with both diastereomeric and enantiomeric excesses of greater than 99%. This new enzyme is of immediate value in developing a practical biocatalytic route to the side chains of statin drugs, such as Lipitor®.

Free-radical addition of phosphine sulfides to aryl and hetaryl acetylenes: unprecedented stereoselectivity

Here, we report on the stereoselective free-radical addition of secondary phosphine sulfide 1 to aryl and hetaryl acetylenes 2a–c. When initiated by azaisobutyronitrile (AIBN, 60–65 °C), the reaction affords Z-isomers of monoadducts 3a–c in high yields (93–96%) and selectivity (~97%) (Scheme 1).† Under analogous conditions, oct-1-yne reacts with phosphine sulfide 1 non-selectively to give almost quantitatively Eand Z-isomers of oct-1-enyl(diphenethyl)phosphine sulfide in a ratio of 1:1. The stereoselectivity of the addition in the case of aryl acetylenes can be rationalised as follows (Scheme 2): initial radicaladduct A is capable of additional stabilising by resonance interaction with adjacent benzene ring (A1) and further through-space spin transfer onto the P=S moiety thus closing the six-membered ring radical species (A2, A3) or A4 with the spin distributed over the three multiple bonds and two heteroatoms (P, S). P Ph

ChemInform Abstract: Unprecedented Stereoselectivity in the Staudinger Reaction with Polycyclic Aromatic Imines.

Cycloaddition of imines derived from polycyclic aromatic amines with acid chloride (or equivalent) in the presence of triethylamine at −78°C to room temperature unexpectedly produced trans-β-lactams.

Unprecedented stereoselectivity in the Staudinger reaction with polycyclic aromatic imines

Cycloaddition of imines derived from polycyclic aromatic amines with acid chloride (or equivalent) in the presence of triethylamine at −78°C to room temperature unexpectedly produced trans-β-lactams.

Stereochemical control in the metallohalocarbenoid route to linear enediynes

Methods for the stereoselective preparation and unmasking of disubstituted Z enediynes are reported. The origins of the unprecedented stereoselectivity of the process are uncovered.

Control of Carbene Reactivity by Crystals. A Highly Selective 1,2-H Shift in the Solid-to-Solid Reaction of 1-(4‘-Biphenylyl)-2-phenyldiazopropane to (Z)-1-(4‘-Biphenylyl)-2-phenylpropene

Ruby red polycrystalline samples of 1-(4‘-biphenylyl)-2-phenyldiazopropane (1a) efficiently transform into colorless (Z)-1-(4‘-biphenylyl)-2-phenylpropene [(Z)-3a] in up to 96% yield in a highly selective photochemical solid-to-solid reaction. The solid state reaction was shown to proceed via a carbene intermediate, and it was formulated as a 1,2-H shift with unprecedented stereoselectivity. It was shown that irradiation of 1a in inert solvents gives products via 1,2-H shifts [(Z)-3a and (E)-3a] and 1,2-Ph migrations [(Z)-4a and (E)-4a] in yields that vary strongly with the polarity of solvent. Irradiation of 1a in ethanol gave similar products along with ethers 5a from insertion of the carbene into the EtO−H bond.

ChemInform Abstract: Unprecedented Stereoselectivity in the Reaction of the Novel Diboron Reagent ‐ 1,6‐Bis(dialkylboryl)‐2,4‐hexadiene ‐ with Carbonyl Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Unprecedented Stereoselectivity in the Addition of Organoiron(II) Reagents to Cyclohexanone Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Unprecedented stereoselectivity in the addition of organoiron(II) reagents to cyclohexanone derivatives

Download options Please wait... Article information DOI https://doi.org/10.1039/C39930000328 Article type Paper Download Citation J. Chem. Soc., Chem. Commun., 1993, 328-330 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Unprecedented stereoselectivity in the addition of organoiron(II) reagents to cyclohexanone derivatives M. T. Reetz and S. Stanchev, J. Chem. Soc., Chem. Commun., 1993, 328 DOI: 10.1039/C39930000328 To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Manfred T. Reetz Stephan Stanchev

Unprecedented stereoselectivity in a reaction of a novel diboron compound ? 1,6-bis(dialkylboryl)-2,4-hexadiene with carbonyl compounds

Arylboration of carbonyl compounds with a novel diboron reagent — 1,6-bis(dipropylboryl)-2,4-hexadiene — proceeds in a regio- and stereospecific way to give exclusivelyd,l-diastereomers of the corresponding 2,3-divinylsubstituted 1,4-diols. Their iodocyclization allowed preparation of 3,7-dioxabicyclo[3.3.0]octane derivatives withcis-junction of the tetrahydrofuran rings.