Iodolactonization Reaction Research Articles

Synthesis of Benzodioxepinones and Benzoxazepinones via Tandem Oxidation and Iodolactonization of 2-O/N-tethered Alkenyl Benzaldehyde Mediated by CuI/TBHP.

An efficient methodology for the synthesis of halogenated benzodioxepinones and benzoxazecinones has been developed via tandem oxidation and iodolactonization reaction of 2-O/N-tethered alkenyl benzaldehydes mediated by CuI and tertiarybutylhydro-peroxide in acetonitrile at 70 °C in moderate to good yields. The reaction involves initial oxidation of aldehyde to acid followed by iodolactonization. Terminal propargyl ether resulted in a mixture of mono- and diiodido-3-methylene-1,4-dioxepin-5-ones. The post-synthetic modification of the reaction products leads to the formation of corresponding thiocyanate, azide, thioether, and triazole derivatives.

Catalytic enantioselective iodolactonization reactions.

The halolactonization reaction is a useful chemical transformation for the construction of lactones from γ- or δ-substituted alkenoic carboxylic acids or carboxylic esters. Traditionally, the stereoselectivity of these reactions has been controlled by the substrates or the reagents. The substrate-controlled method has been extensively studied and applied in the synthesis of many natural products. However, catalytic, enantioselective iodolactonizations of γ- or δ-substituted alkenoic carboxylic acids have only recently been developed. This review article highlights the advances that have emerged over the last decade.

Synthesis and Reactivity of Oxazinoindolones via Regioselective 6‐exo‐dig Iodolactonization

An efficient protocol for the facile construction of 3,4‐dihydro‐10‐iodo‐3‐iodomethylene‐[1,4]‐oxazino[4,3‐a]indol‐1‐ones has been developed by using a regio‐ and stereoselective iodolactonization reaction. Subsequent palladium cross‐coupling reactions of 3,4‐dihydro‐10‐iodo‐3‐iodomethylene‐[1,4]‐oxazino[4,3‐a]indol‐1‐ones readily afforded functionalized oxazinoindolones.

Aerobic Catalytic Features in Photoredox- and Copper-Catalyzed Iodolactonization Reactions.

Mechanistic evaluations and comparison of two important aerobic catalytic oxidation processes, aerobic copper catalysis and photoredox catalysis, are performed. Interesting and distinct catalytic behaviors were observed for a common reaction of iodolactonization of alkenoic acids. Namely, the aerobic copper catalysis requires the formation of a copper carboxylate, whereas the aerobic photoredox catalysis requires the addition of proton sources to proceed to completion. Furthermore, the iodolactone products obtained from these catalytic processes are extensively derivatized to a number of functionalized lactones, including aryl lactones generated from the nickel-catalyzed reductive coupling with aryl halides.

Enantioselective Halolactonization Reactions using BINOL-Derived Bifunctional Catalysts: Methodology, Diversification, and Applications.

A general protocol is described for inducing enantioselective halolactonizations of unsaturated carboxylic acids using novel bifunctional organic catalysts derived from a chiral binaphthalene scaffold. Bromo- and iodolactonization reactions of diversely substituted, unsaturated carboxylic acids proceed with high degrees of enantioselectivity, regioselectivity, and diastereoselectivity. Notably, these BINOL-derived catalysts are the first to induce the bromo- and iodolactonizations of 5-alkyl-4( Z)-olefinic acids via 5- exo mode cyclizations to give lactones in which new carbon-halogen bonds are created at a stereogenic center with high diastereo- and enantioselectivities. Iodolactonizations of 6-substituted-5( Z)-olefinic acids also occur via 6- exo cyclizations to provide δ-lactones with excellent enantioselectivities. Several notable applications of this halolactonization methodology were developed for desymmetrization, kinetic resolution, and epoxidation of Z-alkenes. The utility of these reactions is demonstrated by their application to a synthesis of precursors of the F-ring subunit of kibdelone C and to the shortest catalytic, enantioselective synthesis of (+)-disparlure reported to date.

Cluster Preface: Alkene Halofunctionalization

Jeffrey N. Johnston is a 1992 graduate of Xavier University where he completed his B.S. Chemistry degree (Honors, summa cum laude). With summer research stints in medicinal, polymer, and inorganic pigment chemistry under his belt, he transitioned to synthetic organic chemistry at The Ohio State University where he worked with Leo Paquette for his graduate work (PhD 1997). He completed postdoctoral studies with ­David Evans at Harvard University (USA) and was supported by an NIH Postdoctoral Fellowship. His independent career began in 1999 at Indiana University, where he was promoted to Professor of Chemistry before moving to Vanderbilt University in 2006. He is currently a Stevenson Professor of Chemistry. The commitment of his students and postdoctoral scholars to the discovery and development of new reactions and reagents, particularly in enantioselective catalysis, have led to numerous honors, including the Cope Scholar Award, a Fellowship from the Japan Society for the Promotion of Science, a Swiss Chemical Society Lectureship, and an Eli Lilly Grantee Award. It was graduate student Mark Dobish's discovery of the chiral proton-catalyzed enantioselective iodolactonization reaction (J. Am Chem. Soc. 2012, 134, 6068) that began his group's exploits of alkene halofunctionalization reactions for the good of chemical synthesis. Tomislav Rovis was born in Zagreb in former Yugoslavia but was largely raised in southern Ontario, Canada. He earned his PhD degree at the University of Toronto (Canada) in 1998 under the direction of Professor Mark Lautens. From 1998–2000, he was an NSERC Postdoctoral Fellow at Harvard University (USA) with Professor David A. Evans. In 2000, he began his independent career at Colorado State University and was promoted in 2005 to Associate Professor and in 2008 to Professor. His group’s accomplishments have been recognized by a number of awards including an Arthur C. Cope Scholar, an NSF CAREER Award, a Fellow of the American Association for the Advancement of Science and a ­Katritzky Young Investigator in Heterocyclic Chemistry. In 2016, he moved to Columbia University where he is currently Professor of Chemistry.

Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

Squaramide catalyzed enantioselective iodolactonization of allenoic acids

An asymmetric iodolactonization reaction of allenoic acids has been extensively studied. Eight different chiral squaramides were prepared in a straightforward manner and investigated as organocatalysts. The reaction protocol is operationally simple to execute and proceeds with up to 76% enantiomeric excess. Several conditions, additives, catalysts, and substrates have been investigated. The best results were observed with 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((1R,2R)-2-(dipentylamino)cyclohexyl)amino)-cyclobut-3-ene-1,2-dione as the catalyst.

A Formal Intermolecular Iodolactonization Reaction Based on a Radical‐Ionic Sequence

AbstractWe report herein a method based on a radical‐ionic sequence between an allylic alcohol and an α‐iodo acid in the presence of substoichiometric amounts of lauroyl peroxide (DLP) to produce an atom transfer radical addition (ATRA) adduct, which subseqently underwent an acid‐mediated lactonization. This approach can be described as a free radical reaction followed by an intermolecular iodolactonization. Twenty‐two experiments were carried out to evaluate the scope of the reaction, which afforded a wide variety of iodo lactones with diverse functionalities. The utility of this approach was demonstrated in the synthesis of the natural product (–)‐de‐O‐methylcentrolobine.

ChemInform Abstract: Formal Synthesis of Degraded Sterol (+)‐Aplykurodinone‐1.

The formal synthesis of aplykurodinone-1 is accomplished starting from a suitably functionalized bicyclic lactone having the requisite cis-fused ring junction with a quaternary chiral center that was assembled following a Cp2TiCl-mediated radical cyclization protocol. Our synthetic route further elaborates implementation of Grubbs ring closing metathesis (RCM), Eschenmoser-Claisen rearrangement and iodo-lactonization reactions for the synthesis of the final tricyclic precursor of the target molecule. (C) 2015 Elsevier Ltd. All rights reserved.

Formal synthesis of degraded sterol (+)-aplykurodinone-1

The formal synthesis of aplykurodinone-1 is accomplished starting from a suitably functionalized bicyclic lactone having the requisite cis-fused ring junction with a quaternary chiral center that was assembled following a Cp2TiCl-mediated radical cyclization protocol. Our synthetic route further elaborates implementation of Grubbs ring closing metathesis (RCM), Eschenmoser-Claisen rearrangement and iodolactonization reactions for the synthesis of the final tricyclic precursor of the target molecule.

Concentration and purification of polyunsaturated fatty acids from squid liver processing wastes

Eicosapentaenoic (EPA, 20:5 n‐3) and docosahexaenoic (DHA, 22:6 n‐3) acids were extracted from processing wastes of the liver of the squid Berryteuthis magister. The process included three steps: concentration of the total polyunsaturated fatty acids (PUFA) with urea; separation of individual FA by iodolactonization method, and obtainment of highly purified EPA and DHA by preparative HPLC. Concentration of the acids with urea was carried out at a ratio of urea/FA 3:1 at temperatures of 0 and −20°C, this allowed us to raise the concentration of EPA and DHA from 7.8 and 6.5% to 32.5 and 32.0%, respectively. The iodolactonization reaction was used to obtain from the concentrate individual preparations with concentrations of 93.4% for EPA and 95.6% for DHA; the total yields of the original FA were 50.7 and 41.7%, respectively. Differences in the rates of formation of γ‐ and δ‐iodolactones made a sequential extraction possible, first of DHA from the total PUFA, then of EPA from the remaining acids. Purification of the obtained PUFA products to more than 99% purity was conducted by preparative HPLC.Practical applications: The proposed three‐step procedure for separating EPA and DHA is designed to produce n‐3 PUFA concentrates and highly purified EPA and DHA. The obtained products can be recommended for scientific experiments in vitro.The proposed three‐step procedure for separating EPA and DHA is designed to produce n‐3 PUFA concentrates and highly purified EPA and DHA.

ChemInform Abstract: An Asymmetric Iodolactonization Reaction Catalyzed by a Zinc Bis‐proline—Phenol Complex.

AbstractThe application of Trost′s di‐nuclear zinc complex in catalytic asymmetric iodocyclizations of 5‐substituted 5‐hexenoic acid derivatives using NIS is demonstrated.

Jatrophane Diterpenes: Preparation of the Western Fragment of Pl‐3

AbstractJatrophane diterpenes are structurally intriguing natural products with promising biological properties. Herein, the synthesis of the western fragment of the Euphorbiaceae constituent Pl‐3 starting from (1R,5S)‐bicyclo[3.2.0]hept‐2‐en‐6‐one is described. Key steps in the sequence include a Baeyer–Villiger oxidation, an iodolactonization reaction, and the installation of the northern side chain through the addition of a lithiated vinyl bromide. The overall efficiency of the route is increased by taking advantage of latent symmetry.

Enantioselective iodolactonization of allenoic acids.

An enantioselective iodolactonization reaction of allenoic acids has been developed using a trisimidazoline catalyst and I2. Our mechanistic study suggests the involvement of a π-allyl cation intermediate in this reaction system.

An asymmetric iodolactonization reaction catalyzed by a zinc bis-proline–phenol complex

The intramolecular zinc bis-proline-phenol complex 2a was found to promote enantioselective iodolactonization reactions of both electron-rich and electron-poor 5-aryl-5-hexenoic acids affording δ-iodolactones in good chemical yields with up to 82% enantiomeric excess. The reactions were found to be insensitive to air and moisture, providing an experimentally simple protocol for synthetically useful compounds.

ChemInform Abstract: Achiral Counterion Control of Enantioselectivity in a Broensted Acid‐Catalyzed Iodolactonization.

AbstractThe combination of a chiral ammonium cation and the achiral triflimide anion present in catalyst (I) affords the highest enantioselectivity in the iodolactonization reaction of acid (IIa) compared to eight other combinations of the cation with achiral sulfonate counterions.

1,6-Asymmetric induction: A higher enantioselective synthesis of γ-butyrolactone

A novel 1,6-asymmetric induction has been observed in the iodolactonization of γ, delta;-unsaturated amides. The optically active γ-butyrolactone was synthesized by employing iodolactonization reaction as a key step.

Lewis base catalysis of bromo- and iodolactonization, and cycloetherification

Lewis base catalyzed bromo- and iodolactonization reactions have been developed and the effects of catalyst structure on rate and cyclization selectivity have been systematically explored. The effects of substrate structure on halolactonization reactions and the interaction of those effects with the effects of catalyst structure have been investigated, leading to synthetically useful improvements in cyclization selectivity. The knowledge acquired was applied to the development of Lewis base catalyzed bromo- and iodocycloetherification reactions. The ability of some of the surveyed catalysts to influence the cyclization selectivity of halolactonization reactions demonstrates their presence in the transition structure of the product-determining cyclization step. This observation implies that chiral derivatives of these catalysts have the potential to provide enantioenriched products regardless of the rates or mechanisms of halonium ion racemization.

ChemInform Abstract: Synthesis of Oxidized Fatty Acid Derivatives via an Iodolactonization Reaction.

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