Intramolecular Oxymercuration Research Articles

A Metathesis Route to (+)‐Orientalol F, a Guaiane Sesquiterpene from Alisma Orientalis

The synthesis of (+)‐orientalol F (1) started with aldehyde 6, which is available from (R)‐limonene in two steps. Wittig reaction of 6 with unsaturated ylide 7 to give a tetraene, and subsequent ring‐closing metathesis yielded hydroazulene 4, selective epoxidation of which gave epoxy ester 3. After generation of the requisite isopropyl unit and regioselective reductive epoxide opening, the derived dienol 2 was used for the installation of the oxygen bridge through intramolecular oxymercuration followed by oxidative demercuration. The resulting allylic alcohol epimers 15 and 16 were readily converted into the target natural product 1 by oxidation/reduction sequences.

Synthesis of bis-tetrahydrofuran core of salzmanolin using intramolecular oxymercuration reaction

The bis-THF core of salzmanolin was commenced from d-glucose as starting material. Stereoselective bis-THF ring has been established following intramolecular oxymercuration as the key reaction.

One‐Pot Stereoselective Double Intramolecular Oxymercuration: Synthesis of Four Isomers of an Unsymmetrical Bis‐Tetrahydrofuran Ring System

AbstractStereoselective one‐pot double intramolecular oxymercuration has been demonstrated to be the key reaction in the efficient preparation of the mono‐hydroxylated bis‐tetrahydrofuran ring system present in asimitrin and salzmanolin, two naturally occurring biologically active nonclassical acetogenins.

Synthesis and application of organomercury haptens for enzyme-linked immunoassay of inorganic and organic mercury

Two organomercury haptens were synthesized via the classical oxymercuration reaction. An intramolecular oxymercuration reaction was the strategy employed to prepare a structurally simple, but chemically robust, organomercury hapten that was conjugated to chicken immunoglobulin G (IgG). The resulting immunogen afforded mouse anti-mercury antibodies that were evaluated in an enzyme-linked immunosorbent assay (ELISA). Antibodies demonstrating high titers were obtained, and various immunoassay parameters were investigated. The sensitivity and selectivity of the resulting antibodies were evaluated by exploring different cross-coupling chemistries and solid-phase synthetic variations. A second hapten was prepared with the intermolecular oxymercuration reaction, and the resulting compound, once coupled to carrier protein, afforded a solid-phase conjugate that revealed the versatility of the mouse anti-mercury antibody. The anti-mercury antibody developed in this study was capable of detecting both mercury(II) salts and organomercury compounds.

Double intramolecular oxymercuration: the first stereoselective synthesis of the C10–C34 fragment of asimitrin

The first stereoselective synthesis of the C10–C34 fragment of asimitrin, a nonclassical acetogenin, has been achieved. A key feature of our approach is the application of stereoselective double intramolecular oxymercuration for the efficient preparation of a mono-hydroxylated unsymmetrical bis-THF ring with two flanking hydroxyl groups. A chelation-controlled Grignard reaction plays a pivotal role in the elaboration of a commercially available carbohydrate.

Double intramolecular oxymercuration: stereoselective synthesis of highly substituted bis-tetrahydrofuran

Stereoselective intramolecular oxymercuration has been demonstrated as the key reaction for the efficient preparation of mono- and dihydroxylated unsymmetrical bis-tetrahydrofuran skeletons present in naturally occurring biologically active acetogenins using carbohydrates. These trans- and syn-selective intramolecular oxymercurations were explored in an enantioselective synthesis of the bis-tetrahydrofuran skeleton of mucoxin.

Total synthesis of zincophorin

Abstract A total synthesis of the naturally occurring ionophore zincophorin has been realized. The key steps are an intramolecular oxymercuration of a cyclopropanemethanol for the elaboration of the tetrahydropyran ring and a Carroll–Claisen rearrangement to control the configuration of the double bond at C20–C21 as well as the stereogenic center at C21.

Total synthesis of zincophorin and its methyl ester.

A total synthesis of the naturally occurring ionophore zincophorin has been realized. The route features an intramolecular oxymercuration of a cyclopropanemethanol and a Carroll-Claisen rearrangement for the respective elaboration of the C1-C12 and C13-C25 subunits, which have been assembled by using a highly diastereoselective titanium-mediated aldol condensation.

Cyclization of Dienols, Polyenes, and Dienyne Mediated by Mercuric Salts: Course of Cyclizations Controlled by Stability of Cationic Intermediates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A new nucleophilic addition/ring-closure sequence. Enantioselective synthesis of 3-deoxy-8-oxatropanes.

[reaction: see text] A study of new nucleophilic addition/ring-closure (NARC) sequences has resulted in the development of a stereoselective synthetic route to 3-deoxy-8-oxatropanes. The new sequences consisted of either a syn or anti aldol addition, employing an omega-alkenoyl sultam, followed by two-step bicyclic ring construction involving, consecutively, ring-closing metathesis and intramolecular oxymercuration.

Cyclization of dienols, polyenes, and dienyne mediated by mercuric salts: course of cyclizations controlled by stability of cationic intermediates

Course of cyclization of dienols, polyenes, and dienyne mediated by mercuric salts were controlled by stability of cationic intermediates and source of mercuric salts. Reaction of ( E)-5,9-dimethyl-4,8-decadiene-1-ol with mercuric acetate gave the intramolecular oxymercuration product, whereas one with mercuric triflate produced the olefin cyclization products.

Organomercury Bioconjugate Synthesis and Characterization by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry

Synthesis of an organomercury hapten and conjugation of the hapten to proteins and peptides is described. Starting with allylamine, synthesis of the organomercury hapten was completed in five steps using readily available and inexpensive reagents. The key transformation in the synthesis, intramolecular oxymercuration, was achieved in good yield and under mild conditions. Hapten conjugation was afforded via disuccinimide active ester coupling chemistry, and the resulting conjugates were analyzed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). To exploit the accurate mass measuring capabilities of MALDI-MS, the conjugates were digested with trypsin prior to analysis. The masses of the peptides resulting from tryptic digestion of the organomercury conjugates were accurately measured, and five hapten attachments were identified in the mass range of 1000-2200 m/z. The organomercury bioconjugate synthesized in this study was designed to contain a stable carbon-metal bond, constituting an underutilized approach for preparing protein-metal complexes and may result in mAbs consisting of unique recognition capabilities.

A Formal Total Synthesis of (‐)‐Dysiherbaine.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Nucleophilic Addition Ring Closure [NARC]‐Based Synthesis of (+)‐Nonactic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Formal Total Synthesis of(-)-Dysiherbaine

A key intermediate hexahydrofuropyran 2 to (-)-dysiherbaine 1 has been synthesized concisely via intramolecular oxymercuration and iodocyclization to install the asymmetric centers at the ring junction and the amino groupin the tetrahydropyran stereoselectively.

A nucleophilic addition ring closure [NARC]-based synthesis of (+) -nonactic acid

Nonactic acid 1 has been synthesized in 12 steps from readily available (S)-(−)-ethyl lactate in 20% overall yield. The key (“NARC”) sequence in this method involved anti-aldol addition of acylsultam 3 with aldehyde 4 followed by intramolecular oxymercuration. The efficiency and selectivity of the anti-aldol reaction was found to be critically dependent upon the ratio of Lewis acid to base. The intramolecular oxymercuration was also found to be highly diastereoselective and was attributed to allylic control consistent with previous studies in our group.

A Synthetic Approach towards the C1–C9 Subunit of Zincophorin

Antibiotics made from cyclopropylmethanols: The C1–C9 subunit (2) of zincophorin (1) has been synthesized by using three key steps: a hydroboration of an enantiomerically enriched isopropenylcyclopropane, an aldol reaction, and an intramolecular oxymercuration of a cyclopropylmethanol.

Formation of Cyclic Acetals from Allylic Hydroxy Phosphonates via Intramolecular Oxymercuration

Treatment of allylic hydroxy phosphonates in aldehyde solution with mercuric trifluoroacetate, followed by the reduction of the organomercurial intermediate, afforded the cyclic acetal derivatives. The reaction displays high diastereo- and regio-selectivity. 31 P NMR studies showed the formation of an intermediate hemiacetal and rapid formation of the organomercurial upon addition of mercuric trifluoroacetate. However, the oxymercuration was reversible, and attempts to remove the excess aldehyde often led to recovery of the starting material. Fortunately, reduction of the organomercurial intermediate with sodium cyanoborohydride in the presence of the aldehyde led to more reproducible yields.

ChemInform Abstract: Intramolecular Oxymercuration of 4‐Hexen‐1‐ols: Kinetic vs. Thermodynamic Products Regulated by Mercuric Salts.

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Intramolecular Oxymercuration of 4-Hexen-1-ols: Kinetic vs. Thermodynamic Products Regulated by Mercuric Salts

The rate and mode of intramolecular oxymercuration of 4-hexen-1-ol derivatives was greatly affected by mercuric salts. Mercuric acetate induced a slow reaction to give substituted tetrahydrofurans via 5-exo-trans cyclization. In contrast, 6-endo-trans cyclization proceeded exclusively by mercuric triflate with or without N,N,N’,N’-tetramethylurea. Mercuric salts mediated hydration of alkenes, so-called oxymercuration, was discovered a century ago. The intramolecular reaction of alkenyl alcohol was also investigated since the beginning of the researches and is now considered as one of the most convenient and promising methods to construct cyclic ethers. We have developed mercuric triflate and demonstrated that it is useful not only for olefin cyclization but also oxymercuration. According to the Baldwin’s rule, the exo-mode cyclization is usually preferred over the endo-mode one, and therefore, cyclic ethers with smaller ring size have been produced predominantly. Now we would like to describe that the nature of mercuric salts greatly affected the rate and cyclization mode in the competition between 5-exo-mode and 6-endo-mode oxymercuration of 4-hexen-1-ol derivatives. When the reaction of (E)-1,1-dibenzyl-4-hexen-1-ol (1) with mercuric triflate was carried out, quick reaction took place to give two diastereomers (2) and (3), while the reaction with mercuric acetate afforded 2 as a sole product (Scheme 1). Since oxymercuration usually produces the trans-cyclization product such as 2 and the cis-adduct is usually obtained only when strained alkenes such as norbornene † This paper is dedicated to Professor Sho Ito on the occasion of his 77 birthday (“Ki-Ju”).