Oxidative Dearomatization Of Phenols Research Articles

Elucidation of a Dearomatization Route in the Biosynthesis of Oxysporidinone Involving a TenA-like Cytochrome P450 Enzyme.

Oxidative dearomatization of phenols is an important transformation for synthesis of complex molecules. Oxysporidinone and related 2-pyridones are featured with a hydroxy-substituted cyclohexanone ring, which is proposed from dearomatization of phenol. However, detailed biochemical characterization of this process is still undiscovered. Herein, we identified oxysporidinone biosynthetic gene cluster in Fusarium oxysporum by regulator activation and gene knockout study. Through in vivo and in vitro study, we confirmed that the phenol dearomatization process involves two enzymes. OsdM, as a TenA-like cytochrome P450 expected with ring-expansion activity, converts the phenol ring and the 4-hydroxy-2-pyridone core into an unexpected fused [6-5-6] ring system. OsdN, on the other hand, catalyses two successive ene-reductions, which is followed by hydroxylation via OsdM. This new route enriches current knowledge on enzymatic phenol dearomatization and TenA-like P450s mechanism.

Development of a Catalytic Ester Activation Protocol for the Efficient Formation of Amide Bonds using an Ar−I/HF⋅pyridine/ mCPBA System

AbstractA new catalytic approach for the activation of esters, that possess a p‐hydroxyphenyl group as a potential activating group on the ester residue, was developed and applied to the efficient synthesis of amides and peptides. A characteristic feature of this protocol is the in‐situ generation of a hypervalent iodine(III) species using an Ar−I/HF⋅pyridine/mCPBA system. A reactive acyl fluoride intermediate is smoothly generated via the oxidative dearomatization of phenols in the presence of a catalytic amount of 4‐iodoanisole, thereby affording various amides and peptides including sterically hindered derivatives.

Studies toward the Total Syntheses of Calyciphylline D-Type Daphniphyllum Alkaloids.

An efficient construction of an aza-[5.7.6.5] tetracyclic core structure of calyciphylline D-type Daphniphyllum alkaloids has been achieved. The synthetic route features a diastereoselective cyclopropanation, efficient construction of the core bridged 8-aza-[3.2.1]octane skeleton through a [3 + 2] IMCC strategy, oxidative dearomatization of phenol, and gram-scale preparation in each step.

Mechanistic Study on the Bidentate Nitrogen-Ligated Iodine(V) Reagent Promoted Oxidative Dearomatization of Phenols

Mechanistic Study on the Bidentate Nitrogen-Ligated Iodine(V) Reagent Promoted Oxidative Dearomatization of Phenols

Site‐selective Oxidative Dearomatization of Phenols and Naphthols into ortho‐Quinols or Epoxy ortho‐Quinols using Oxone as the Source of Dimethyldioxirane

AbstractA novel reactivity of dimethyldioxirane, generated in situ from Oxone and acetone, with substituted phenols and naphthols is reported. This methodology allowed the synthesis of ortho‐quinols or epoxy ortho‐quinols from a site‐selective oxidative dearomatization process, with good yields under very mild conditions. A short total synthesis of natural product lacinilene C methyl ether is also described using this process as the key step.magnified image

Enantioselective Synthesis of Cyclohexadienone Containing Spiroketals via DyKat Ketalization/oxa-Michael Addition Cascade.

An oxidative dearomatization of phenol followed by a dynamic kinetic (DyKat) ketalization/oxa-Michael addition cascade using cinchona alkaloid-based chiral bifunctional amino-squaramide catalysts is reported. A broad array of sterically hindered [5,5]-spiroketals attached to a cyclohexadienone moiety in spiro-fashion is synthesized in an enantiopure form. Further, the methodology was optimized and extended to the corresponding benzannulated [5,5]-spiroketals attached to a cyclohexadienone moiety in spiro-fashion. In general, good yields and excellent diastereoselectivies and enantioselectivities (up to 20:1 dr and up to 99% ee) were obtained.

Total Synthesis of (±)-Prostratin

Summary Prostratin, a highly complex diterpene natural product, is a pre-clinical candidate in developing a cure for HIV-1 infection and also a potent and selective inhibitor of several tumors. Despite nearly 40 years of progress, prostratin and related natural products still present formidable challenges for synthetic chemists. Here, we report a total synthesis of (±)-prostratin that proceeds in 23 steps from cyclopentadiene. The synthetic strategy includes rapid assembly of the tricyclic core and highly controlled establishment of the densely functionalized C ring, featuring an array of stereoselective transformations including alkoxide-guided 1,4-additions and cyclopropane formation. This work should enable further explorations of chemical and biological spaces based on prostratin and related natural products.

Biocatalytic Highly Enantioselective Oxidative Dearomatization of Phenols

Biocatalytic Highly Enantioselective Oxidative Dearomatization of Phenols

Sodium Hypochlorite Pentahydrate Crystals (NaOCl·5H2O): A Convenient and Environmentally Benign Oxidant for Organic Synthesis

The novel oxidant of sodium hypochlorite pentahydrate (NaOCl·5H2O) crystals is now available for industrial and laboratory use. It is superior to conventional aqueous sodium hypochlorite solutions (aq. NaOCl). The crystalline material is 44% NaOCl and contains minimal amounts of sodium hydroxide and sodium chloride, and the aqueous solution, which is prepared from NaOCl·5H2O and water, has a pH of 11–12. Examples of the selective organic synthesis using NaOCl·5H2O involve the oxidations of primary and secondary alcohols, selective oxidations to sulfoxide and sulfone, oxidative cleavage of disulfide to sulfonyl chloride and bromide, oxaziridine synthesis, and oxidative dearomatization of phenols.

Organocatalytic, Enantioselective Synthesis of Cyclohexadienone Containing Hindered Spirocyclic Ethers through an Oxidative Dearomatization/Oxa‐Michael Addition Sequence

AbstractAn unprecedented enantioselective oxa‐Michael reaction of α‐tertiary alcohols using cinchona‐alkaloid‐based chiral bifunctional squaramide catalysts is reported. An oxidative dearomatization of phenol followed by an enantioselective oxa‐Michael addition sequence provided a broad array of chiral sterically hindered tetrahydrofurans and tetrahydropyrans attached to a cyclohexadienone moiety in spiro fashion. In general, good yields and excellent enantioselectivities (up to 99 %) were observed. The chiral oxo‐cycles obtained have easily been transformed into chromans without disturbing the enantioselectivity.

Organocatalytic, Enantioselective Synthesis of Cyclohexadienone Containing Hindered Spirocyclic Ethers through an Oxidative Dearomatization/Oxa-Michael Addition Sequence.

An unprecedented enantioselective oxa-Michael reaction of α-tertiary alcohols using cinchona-alkaloid-based chiral bifunctional squaramide catalysts is reported. An oxidative dearomatization of phenol followed by an enantioselective oxa-Michael addition sequence provided a broad array of chiral sterically hindered tetrahydrofurans and tetrahydropyrans attached to a cyclohexadienone moiety in spiro fashion. In general, good yields and excellent enantioselectivities (up to 99 %) were observed. The chiral oxo-cycles obtained have easily been transformed into chromans without disturbing the enantioselectivity.

ChemInform Abstract: Asymmetric Oxidative Dearomatizations Promoted by Hypervalent Iodine(III) Reagents: An Opportunity for Rational Catalyst Design?

AbstractReview: [57 refs.

ChemInform Abstract: Molecular Complexity and Diversity from Aromatics. The Chemistry of Spiro[cyclohexa‐2,4‐dienone‐6,2′‐oxiranes] and Their Congeners: Cycloaddition and Beyond

AbstractReview: 47 refs.

Molecular Complexity and Diversity from Aromatics. The Chemistry of Spiro[cyclohexa-2,4-dienone-6,2′-oxiranes] and Their Congeners: Cycloaddition and Beyond

The efficient generation of complex molecular architectures from simple precursors is one of the most important aspects in the design and development of synthetic methodologies. The chemistry of reactive species generated by the oxidative dearomatization of phenols, such as <i>o</i>-quinone acetals, 6-acetoxycyclohexa-2,4-di­enones, and their congeners, has stimulated widespread interest among organic chemists, and the use of such reactive species has emerged as a powerful method for the efficient synthesis of complex molecules. Our approach to create molecular complexity and diversity involves the oxidative dearomatization of 2-(hydroxymethyl)phenols to give spiro[cyclohexa-2,4-dienone-6,2′-oxiranes], followed by cycloaddition and transformation of the resulting adducts in the ground and excited states. In this account, we describe the evolution of the methodology and its application which has led to the development of novel and efficient routes to a diverse array of complex molecular architectures from simple aromatics. 1 Introduction 2 Cycloaddition of Cyclohexa-2,4-dienones of Types <b>3</b> and <b>4</b> and Manipulation of the Adducts in the Ground and Excited States 2.1 Cycloaddition of Cyclohexa-2,4-dienones of Types <b>3</b> and <b>4</b>: An Efficient Route to Functionalized and Appended Bicyclo[2.2.2]octanes 2.1.1 Cycloaddition of Cyclohexa-2,4-dienones of Types <b>3</b> and <b>4</b> with Electron-Deficient π-Partners 2.1.2 Cycloaddition of Cyclohexadienones of Type <b>4</b> with Vinyl Ethers and Vinyl Acetate 2.1.3 Cycloaddition of Cyclohexadienones of Types <b>3</b> and <b>4</b> with Acyclic 1,3-Dienes: Direct Entry to Bicyclo[2.2.2]octenones Having an <i>endo</i>-Vinyl Group 2.2 Manipulation of the Oxirane Moiety or the Chloromethyl and Hydroxy Groups in the Adducts: Synthesis of Embellished Bicyclo[2.2.2]octanes 2.3 3,3-Sigmatropic Shift in Bicyclo[2.2.2]octanes: A General Stereoselective Route to Functionalized <i>cis</i>-Decalin Derivatives 2.4 Sigmatropic Rearrangements of β,γ-Enones in Excited States: Stereoselective Routes to Bicyclo[3.3.0]- and Bi­cyclo[4.2.0]octanes and Tricyclic Compounds 3 Synthetic Applications 3.1 Synthesis of Hirsutic Acid C and the Framework of ­Pupukeananes from a Common Precursor 3.2 Chemistry of Fused Spiro[cyclohexa-2,4-dienone-6,2′-oxiranes] and Their Adducts: Synthesis of Propellanes and ­Steroid–Polyquinane Hybrids 3.2.1 A General Route to [3.3.3]- and [4.3.3]Propellanes 3.2.2 Synthesis of Steroid–Polyquinane Hybrids 3.3 Synthesis of Tri- and Tetracyclic Networks of Atisane Diterpenoids 3.3.1 Synthesis of Tricyclo[6.2.2.0^1,6]dodecanes and Their Homologues 3.3.2 Synthesis of the Tetracyclic Network of Atisane Diterpenoids: An Interesting Manifestation of Subtle Control by a Remote Functional Group 3.4 Intramolecular Cycloaddition of Cyclohexa-2,4-dienones: Synthesis of Platencin 4 Summary and Outlook

ChemInform Abstract: An Efficient Oxidative Dearomatization—Radical Cyclization Approach to Symmetrically Substituted Bicyclic Guttiferone Natural Products.

AbstractThe core structure (VI) of guttiferone terpenes such as (VII) is prepared via a diacetoxyiodobenzene‐mediated oxidative dearomatization of phenol (II) and a subsequent radical cyclization of the resulting ketal as key steps.

ChemInform Abstract: Highly Diastereoselective Synthesis of Orthoquinone Monoketals Through λ3‐Iodane‐Mediated Oxidative Dearomatization of Phenols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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: Oxidative Dearomatization of Phenols: Why, How and What For?

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Highly Diastereoselective Synthesis of Orthoquinone Monoketals through λ3‐Iodane‐Mediated Oxidative Dearomatization of Phenols

Highly Diastereoselective Synthesis of Orthoquinone Monoketals through λ³‐Iodane‐Mediated Oxidative Dearomatization of Phenols

Highly Diastereoselective Synthesis of Orthoquinone Monoketals through λ3‐Iodane‐Mediated Oxidative Dearomatization of Phenols

Highly Diastereoselective Synthesis of Orthoquinone Monoketals through λ³‐Iodane‐Mediated Oxidative Dearomatization of Phenols

Oxidative Dearomatization of Phenols: Why, How and What For?

This account reviews our investigations over the last ten years on the selective dearomatization of phenols into cyclohexadienones and its application in natural products synthesis.