Martin Periodinane Research Articles

Dess–Martin Periodinane/Brønsted Acid-Mediated Tandem Oxidation/Cyclization of Homopropargylic Alcohols for Synthesis of Trisubstituted Furans

AbstractA facile, efficient, and metal-free single-flask procedure for the synthesis of trisubstituted furans from simple readily available homopropargylic alcohols is described. A combination of Dess–Martin periodinane, H2O, and TsOH·H2O plays a crucial role in the formation of the trisubstituted furans. The advantages of this method include operational ease, mild reaction conditions, and good functional-group tolerance.

Synthesis of a stretchable polymer crosslinker for reinforced atelocollagen threads

This study describes the novel procedure for synthesizing an aldehyde-containing polyrotaxane (PRβCD1) composed of β-cyclodextrin (βCD) monoaldehyde and polypropylene glycol, and the preparation of atelocollagen threads with enhanced mechanical properties through the use of PRβCD1 as a crosslinker (Col–PRβCD1). For the selective introduction of the aldehyde groups into βCD of the PRβCD1, the comparative study on the oxidation method was initially performed with Dess–Martin Periodinane (DMP) and a redox couple between the (2,2,6,6-tetramethylpiperidin-1-yl)oxyl and iodobenzene derivatives. NMR measurements performed after oxidation of βCD with the DMP indicated the presence of both ketone and aldehyde, while the selective production of the aldehyde groups was achieved by the proposed redox couple. After further improvement of the reaction conditions, the water-soluble PRβCD1 containing aldehyde groups as the only crosslinkable sites was successfully synthesized. Interestingly, the fracture strain and stress, and toughness of the atelocollagen threads were enhanced after crosslinking with PRβCD1. The observed mechanical properties of Col–PRβCD1 reflect the slide-ring features of the polyrotaxane. Overall, this study provides important insights into the synthesis of crosslinkable polyrotaxanes and their applicability as biomaterials.

Thiazole-5-carbaldehyde Synthesis by Cascade Annulation of Enaminones and KSCN with Dess-Martin Periodinane Reagent.

The Dess-Martin periodinane (DMP) reagent-mediated reactions of tertiary enaminones with potassium thiocyanate for the synthesis of thiazole-5-carbaldehydes are developed. The product formation involves cascade hydroxyl thiocyanation of the C═C double bond, intramolecular hydroamination of the C≡N bond, and thiazole annulation by condensation on the ketone carbonyl site, representing novel reaction pathways in the reactions between enaminones and thiocyanate salt. DMP plays dual roles in mediating the free radical thiocyanation and inducing the unconventional selective thiazole-5-carbaldehyde formation by masking the in situ generated formyl group during the reaction process.

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

A novel tyrosine hyperoxidation enables selective peptide cleavage.

A novel tyrosine hyperoxidation enabling selective peptide cleavage is reported. The scission of the N-terminal amide bond of tyrosine was achieved with Dess–Martin periodinane under mild conditions, generating a C-terminal peptide fragment bearing the unprecedented hyperoxidized tyrosine motif, 4,5,6,7-tetraoxo-1H-indole-2-carboxamide, along with an intact N-terminal peptide fragment. This reaction proceeds with high site-selectivity for tyrosine and exhibits broad substrate scope for various peptides, including those containing post-translational modifications. More importantly, this oxidative cleavage was successfully applied to enable sequencing of three naturally occurring cyclic peptides, including one depsipeptide and one lipopeptide. The linearized peptides generated from the cleavage reaction significantly simplify cyclic peptide sequencing by MS/MS, thus providing a robust tool to facilitate rapid sequence determination of diverse cyclic peptides containing tyrosine. Furthermore, the highly electrophilic nature of the hyperoxidized tyrosine unit disclosed in this work renders it an important electrophilic target for the selective bioconjugation or synthetic manipulation of peptides containing this unit.

Unified Total Syntheses of (±)-Sessilifoliamides B, C, and D.

The first total syntheses of the Stemona alkaloids sessilifoliamides B and D and the second synthesis of sessilifoliamide C have been completed from a simple pyrrole substrate. The bicyclic lactam core was prepared on a gram scale via a Brønsted acid mediated cyclization and controlled oxidation with Dess-Martin periodinane. This delivered sessilifoliamide C (and its C-11 epimer) in 24% yield over 11 steps, and sessilifoliamides B and D in 13 and 17 steps, respectively.

A Concise Review of Hypervalent Iodine with Special Reference to Dess- Martin Periodinane

The chemistry of hypervalent iodine compounds has been experiencing considerable attention of organic chemists during the past few years. Hypervalent iodine reagents have found ubiquitous applications in organic synthesis because of their mild and highly chemoselective oxidizing properties, easy commercial availability, and environmental benign character. Along with oxidation of alcohol, they have also shown to be useful in number of organic transformations which include oxidative functionalization of carbonyl compounds, catalytic imidations, cyclization, oxidative coupling of phenols, amines and related compounds. Among various hypervalent iodine reagents, iodine-V compounds (λ5-iodanes) have attracted much attention in recent years. This review narrates the particular advances in iodine (V) reagents with special emphasis on the use of DMP in organic transformations.

HFO‐1234yf as a CF3‐Building Block: Synthesis and Chemistry of CF3‐Ynones

Reaction of low cost, readily available 4th generation refrigerant gas 2,3,3,3‐tetrafluoropropene (HFO‐1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3‐trifluoropropynide, addition of which to a range of aldehydes formed CF3‐alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess–Martin periodinane (DMP) to give substituted CF3‐ynones with minimal purification required. Michael‐type additions of alcohol and amine nucleophiles to CF3‐ynones are rapid and selective, affording a range of CF3‐enone ethers and enaminones in excellent yields with high stereoselectivity for the Z‐isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF3‐substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti‐arthritis drug celecoxib from HFO‐1234yf in just three steps.

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration-oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles.

Isoxazolidines represent a very important class of N/O-containing heterocycles used as the key intermediates in the synthesis of more complex cyclic and acyclic compounds, including various biologically active molecules. Here, we present a fast and highly stereoselective approach towards both C-3/4-cis and C-3/4-trans isomers of 3-substituted isoxazolidin-4-ols. The strategy relies on a highly regio- and trans-stereoselective hydroboration–oxidation reaction of the 4,5-unsubstituted 2,3-dihydroisoxazoles with basic hydrogen peroxide. The consecutive oxidation/reduction route, sequentially employing Dess–Martin periodinane and ʟ-selectride, is used for the inversion of the C-3/4-trans relative configuration of the isoxazolidine ring. The significance of the method lies in its variability and applicability to a concise synthesis of various 4-hydroxyisoxazolidines, starting from the readily available C-alkyl/aryl-nitrones. The resemblance to 3-hydroxypyrrolidines certainly makes the 4-hydroxyisoxazolidines important and valuable structural fragments in drug discovery.

Aliphatic α‐Boryl‐α‐bromoketones: Synthesis and Reactivity

A protocol for the preparation of α‐boryl‐α‐bromoketones from alkenyl MIDA boronates was developed and applied to functionalized aliphatic derivatives. The reaction sequence included regioselective hydroxybromination of olefin moiety, followed by oxidation of alcohol group with Dess–Martin periodinane. The target trifunctional boronate‐containing derivatives were obtained in up to 94 % yield over two steps starting from alkenyl MIDA boronates. In some cases, functional groups present in the substrate participated in the bromohydroxylation step via intramolecular nucleophilic attack at the bromonium cation leading to cyclic products. Additionally, the reactivity of aliphatic α‐boryl‐α‐bromoketones was illustrated by nucleophilic substitution at the α‐C atom and heterocyclization reactions.

Recent Applications of the Zhdankin Reagent in Organic Synthesis

Hypervalent iodine reagents have rapidly become vital synthetic tools in organic chemistry as stoichiometric oxidants and electrophilic sources of various functional groups such as F, CN, and alkynes.[ 1 – 3 ] Many such reagents are now known, with prominent examples such as Dess–Martin periodinane and 2-iodoxybenzoic acid being commercially available. In 1996, the Zhdankin reagent, 1-azido-1,2-benziodoxol-3(1H)-one (3) was first prepared[ 4 ] from 1-hydroxy-1,2-benziodoxol-3(1H)-one (1) and trimethylsilyl azide ( Scheme 1 ). This hypervalent iodine compound can also be efficiently prepared from iodosobenzoic acid (2).[ 5 ] Compound 3 has been shown to primarily act as a source of radical azide.[ 5 , 6 ] Radical reactivity can be initiated thermally or with a peroxide catalyst. The use of this reagent in synthesis has grown considerably since 2013, which may relate to the rise of photoredox catalysis. The latter methodology allows the generation of radicals under particularly mild conditions. The Zhdankin reagent is frequently employed in tandem with a metal catalyst such as copper[ 7 – 12 ] or iron.[ 13 , 14 ] This article highlights some notable applications of molecule 3 that have appeared since 2016.

A synthesis of cephalostatin 1

A synthesis of cephalostatin 1 from hecogenin is described in detail. The gram-scale synthesis of south part features a Baeyer–Villiger oxidation of hecogenin to 16,20-diol, a selective oxidation of C16OH with Dess–Martin periodinane, a Rh(I)-catalyzed C15C16 double bond shift to C14C15 position, and a Hg(OAc)2-mediated spiroketal formation from cyclic enol ethers with alkenyl side chain at 2-position. Key transformations in the synthesis of north part, also on gram scale, include an abnormal Baeyer–Villiger oxidation of hecogenin to the corresponding dinorcholanic lactone, where a catalytic amount of iodine acts as a traceless and catalytic switch, an umpolung of steroidal 22-aldehyde to forge C22C23 bond with good stereochemical control, a cascade spiroketal-forming process to establish DEF rings in one operation, and a selective oxidation of C3OH. There are also other noteworthy transformations that, although not used in our final route, are valuable and could be applied to other syntheses, including: intra- or intermolecular SN2′ processes of C14-heteroatom-substituted C15C16 alkenes, an unprecedented rearrangement of β-adduct of D-ring dienes and singlet oxygen, a chelation-controlled methylallylation of C23 aldehyde, and so on.

Oxidation Catalysis by an Aerobically Generated Dess–Martin Periodinane Analogue

AbstractHypervalent iodine(V) reagents, such as Dess–Martin periodinane (DMP) and 2‐iodoxybenzoic acid (IBX), are broadly useful oxidants in chemical synthesis. Development of strategies to generate these reagents from dioxygen (O2) would immediately enable use of O2 as a terminal oxidant in a broad array of substrate oxidation reactions. Recently we disclosed the aerobic synthesis of I(III) reagents by intercepting reactive oxidants generated during aldehyde autoxidation. In this work, aerobic oxidation of iodobenzenes is coupled with disproportionation of the initially generated I(III) compounds to generate I(V) reagents. The aerobically generated I(V) reagents exhibit substrate oxidation chemistry analogous to that of DMP. The developed aerobic generation of I(V) has enabled the first application of I(V) intermediates in aerobic oxidation catalysis.

Stereoselective Synthesis of Northern Fragment of Eribulin Mesylate from d-Mannose

Stereoselective synthesis of northern fragment of eribulin mesylate is reported by coupling of the C1–C13 fragment with the C28–C35 fragment. The key steps involved in this synthesis are butyllithium-facilitated coupling between sulfone and aldehyde, then Dess–Martin periodinane oxidation followed by samarium(II) iodide mediated desulfonylation.

Desymmetrization of Hepta-1,6-dien-4-ol by a Highly Stereo­selective Tandem Prins–Ritter Cyclization: Access to New THP Acetamides

Prins–Ritter cyclization performed from hepta-1,6-dien-4-ol and various aldehydes, promoted by bismuth(II) triflate, afforded N-(tetrahydropyranyl)acetamides in moderate to high yields. Subsequent Wacker-type oxidation using Dess–Martin periodinane (DMP) delivered the corresponding ketones.

Diethylamine Dess–Martin periodinane: an efficient catalyst–oxidant combination in a sequential, one-pot synthesis of difficult to access 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines at ambient temperature

A problem solving approach towards high yielding synthesis of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines is described. Simple isolation and avoidance of chromatographic purification are the noteworthy advantages.

ChemInform Abstract: Hypervalent Iodine as a Terminal Oxidant in Wacker‐Type Oxidation of Terminal Olefins to Methyl Ketones.

AbstractA Markovnikov‐selective oxidation of terminal olefins by a combination of palladium(II) acetate and Dess—Martin periodinane is described.

Catalytic Hypervalent Iodine Promoters Lead to Styrene Dimerization and the Formation of Tri‐ and Tetrasubstituted Cyclobutanes

AbstractReported herein is that the use of catalytic quantities of hypervalent iodine reagents (phenyliodine diacetate or Dess–Martin periodinane) allows the rapid and stereoselective formation of cyclobutanes under very mild reaction conditions. The presence of a fluorinated solvent is essential for the success of these reactions which form unsymmetrical tri‐ and tetrasubstituted cyclobutanes through a heterodimerization process involving two different alkenes.

ChemInform Abstract: Alkynyl Trifluoromethyl Selenide Synthesis via Oxidative Trifluoromethylselenolation of Terminal Alkynes.

The synthesis of alkynyl trifluoromethyl selenides by Cu-mediated oxidative trifluoromethylselenolation of terminal alkynes is reported. Treatment of [(bpy)Cu(SeCF3)]2 with various terminal alkynes in the presence of an oxidant, Dess–Martin periodinane, led to the formation of trifluoromethylselenolated acetylenes bearing sensitive moieties such as alkoxy, halogens, trifluoromethyl, and heterocyclic groups.

A Study of the Reactivity of Polyhydroxylated Sterol Derivatives

AbstractA detailed study of regiospecific silylation, oxidation, and reduction of sterols is reported. The different reactivity of 2α and 3α hydroxy groups is demonstrated on a 2α,3α‐dihydroxy‐5α‐pregnane‐6,20‐dione as a model substrate. A regiospecific silylation of the 2α‐alcohol occurred when silyl chloride was used under mild reaction conditions. The selective oxidation of one of the 2α,3α‐diols by dimethyldioxirane or the Dess–Martin periodinane led to a mixture of α‐hydroxyketones with high prevalence of 3,6,20‐trione over 2,6,20‐trione in the ratio 10:1. A regiospecific reduction of a model substrate by lithium tri‐tert‐butoxyaluminium hydride gives the C6 alcohol.