Endocyclic Double Bond Research Articles

ChemInform Abstract: Systematic Study on Free Radical Hydrothiolation of Unsaturated Monosaccharide Derivatives with Exo‐ and Endocyclic Double Bonds.

AbstractThe photoinduced radical‐mediated hydrothiolation reactions show highly varying overall conversions depending not only on the substitution pattern and electron‐density of the double bond but also on the nature and the substitution pattern of the thiol partner.

ChemInform Abstract: Intramolecular Mizoroki—Heck Reaction in the Regioselective Synthesis of 4‐Alkylidene‐tetrahydroquinolines.

The Mizoroki–Heck reaction of N-alkenyl-substituted 2-haloanilines is an effective protocol for the synthesis of substituted 4-alkylidene-tetrahydroquinoline derivatives, avoiding isomerization and oxidation. When non-substituted alkenes are used, the regioselectivity of the reaction can be directed towards the formation of an exocyclic or endocyclic double bond by choosing an adequate catalytic system. When the double bond is substituted by an amide moiety, the exocyclic double bond of E geometry is obtained selectively. Thus, this protocol efficiently synthesizes a series of 2-substituted tetrahydroquinolines with an exo α,β-unsaturated amide moiety at the C-4 position.

Influence of Humidity, Temperature, and Radicals on the Formation and Thermal Properties of Secondary Organic Aerosol (SOA) from Ozonolysis of β-Pinene

The influence of water and radicals on SOAs produced by β-pinene ozonolysis was investigated at 298 and 288 K using a laminar flow reactor. A volatility tandem differential mobility analyzer (VTDMA) was used to measure the evaporation of the SOA, enabling the parametrization of its volatility properties. The parameters extracted included the temperature at which 50% of the aerosol had evaporated (T(VFR0.5)) and the slope factor (S(VFR)). An increase in S(VFR) indicates a broader distribution of vapor pressures for the aerosol constituents. Reducing the reaction temperature increased S(VFR) and decreased T(VFR0.5) under humid conditions but had less effect on T(VFR0.5) under dry conditions. In general, higher water concentrations gave lower T(VFR0.5) values, more negative S(VFR) values, and a reduction in total SOA production. The radical conditions were changed by introducing OH scavengers to generate systems with and without OH radicals and with different [HO2]/[RO2] ratios. The presence of a scavenger and lower [HO2]/[RO2] ratio reduced SOA production. Observed changes in S(VFR) values could be linked to the more complex chemistry that occurs in the absence of a scavenger and indicated that additional HO2 chemistry gives products with a wider range of vapor pressures. Updates to existing ozonolysis mechanisms with routes that describe the observed responses to water and radical conditions for monoterpenes with endocyclic and exocyclic double bonds are discussed.

Iodine-Catalyzed Prins Cyclization of Homoallylic Alcohols and Aldehydes

The iodine-catalyzed Prins cyclization of homoallylic alcohols and aldehydes was investigated under metal-free conditions and without additives. Anhydrous conditions and inert atmosphere are not required. The reaction of 2-(3,4-dihydronaphthalen-1-yl)propan-1-ol and 21 aldehydes (aliphatic and aromatic) in CH2Cl2 in the presence of 5 mol % of iodine gave 1,4,5,6-tetrahydro-2H-benzo[f]isochromenes in 54%–86% yield. Under similar conditions, the Prins cyclization of six alcohols containing an endocyclic double bond (primary, secondary, or tertiary) led to dihydropyrans in 52%–91% yield. The acyclic homoallylic alcohols gave 4-iodo-tetrahydropyran in 29%–41% yield in the presence of 50 mol % of iodine. This type of substrate is the main limitation of the methodology. The relative configuration of the products was assigned by NMR and X-ray analysis. The mechanism and the ratio of the products are discussed, based on DFT calculations.

Intramolecular Mizoroki–Heck Reaction in the Regioselective Synthesis of 4‐Alkylidene‐tetrahydroquinolines

AbstractThe Mizoroki–Heck reaction of N‐alkenyl‐substituted 2‐haloanilines is an effective protocol for the synthesis of substituted 4‐alkylidene‐tetrahydroquinoline derivatives, avoiding isomerization and oxidation. When non‐substituted alkenes are used, the regioselectivity of the reaction can be directed towards the formation of an exocyclic or endocyclic double bond by choosing an adequate catalytic system. When the double bond is substituted by an amide moiety, the exocyclic double bond of E geometry is obtained selectively. Thus, this protocol efficiently synthesizes a series of 2‐substituted tetrahydroquinolines with an exo α,β‐unsaturated amide moiety at the C‐4 position.

Gibberellin analogues by reaction of 7-oxo-diterpenes with diacetoxyiodobenzene

In this work, the reaction of 7-oxo-diterpenes with diacetoxyiodobenzene (DIB) has been proved to be a good method for the preparation of gibberellin analogues, which can be applied to diterpenes with endocyclic or exocyclic double bonds. It has been studied with ent-kaur-16-ene, ent-trachylobane and ent-atis-16-ene diterpenes. Thus, the reaction of 7-oxo-ent-kaur-16-en-18-oic acid methyl ester and 7-oxo-ent-trachyloban-16-en-18-oic acid methyl ester with this reagent affords 4-epi-gibberellin A12 dimethyl ester and 4-epi-trachylobagibberellin A12 dimethyl ester, respectively. In some cases, especially with compounds functionalized at C-19, alternative reactions lead to the introduction in the substrate of a conjugated 5,6-double bond or to the formation of a ketal at the 6-position. Thus, the formation of gibberellin analogues, dehydrogenation products or 6-ketal derivatives depend on the neighbouring group participation of the C-18 (equatorial) and C-19 (axial) substituents at C-4.

Systematic study on free radical hydrothiolation of unsaturated monosaccharide derivatives with exo- and endocyclic double bonds

Exo- and endocyclic double bonds of glycals and terminal double bonds of enoses were reacted with various thiols by irradiation with UV light in the presence of a cleavable photoinitiator. The photoinduced radical-mediated hydrothiolation reactions showed highly varying overall conversions depending not only on the substitution pattern and electron-density of the double bond but also on the nature and substitution pattern of the thiol partner. Out of the applied thiols thiophenol, producing the highly stabilized thiyl radical, exhibited the lowest reactivity toward each type of alkene. In most cases, the hydrothiolations took place with full regio- and stereoselectivities. Successful addition of 1,2 : 3,4-di-O-isopropylidene-6-thio-α-d-galactopyranose to a 2,3-unsaturated N-acetylneuraminic acid derivative, providing a (3 → 6)-S-linked pseudodisaccharide, demonstrated that the endocyclic double bond of Neu5Ac-2-ene, bearing an electron-withdrawing substituent, shows sufficient reactivity in the photoinduced thiol-ene coupling reaction.

A Formal Synthesis of Iridoid 9‐Deoxygelsemide

AbstractA formal total synthesis of iridoid 9‐deoxygelsemide has been accomplished. Our approach features the use of (S)‐carvone as starting material, Favorskii rearrangement to construct the functionalized cyclopentane core, Chugeav elimination to introduce the endocyclic double bond, and the ring‐opening reaction of epoxide to build the second five‐membered ring.

Synthesis of S-Linked Glycoconjugates and S-Disaccharides by Thiol–Ene Coupling Reaction of Enoses

Free-radical hydrothiolation of the endocyclic double bond of enoses is reported. Reaction between 2-acetoxy-D-glucal and a range of thiols including amino acid, peptide, glycosyl thiols, and sugars with primary or secondary thiol functions gave S-linked α-glucoconjugates and S-disaccharides with full regio- and stereoselectivity. Addition of glycosyl thiols to a 2,3-unsaturated glycoside also proceeded with good selectivity and afforded a series of 3-deoxy-S-disaccharides.

Synthesis of pyrazolo[1,3,2]diazaphosphinin-4-ones

It was found that phosphinimidic isocyanates based on 3-, 4-, and 5-aminopyrazoles could undergo intramolecular heterocyclization to yield previously unknown pyrazolo[1,3,2]diazaphosphorin-4-ones containing an endocyclic PN double bond. It was shown that phosphinimidic isocyanate based on 4-aminopyrazole, in which there are two positions (3 and 5) available for the cyclization, reacts exclusively at the 5-carbon atom. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:210–215, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21005

Addition polymerization of norbornene, 5-vinyl-2-norbornene and 2-methoxycarbonyl-5-norbornene with a catalyst based on a palladium(0) precursor complex

Pd(dibenzylideneacetone) 2, when activated in situ with 1 equiv of [CPh 3][B(C 6F 5) 4] in the presence of 1 equiv of P(C 6H 11) 3, efficiently catalyzed the addition polymerization and copolymerization of norbornene and its derivatives. Homopolymerization of 5-vinyl-2-norbornene took place regio-selectively with the endo-cyclic double bond to give high-molecular weight polymers, while the exocyclic double bond remained intact so that the resulting polymer had pendent vinyl groups along the polymer chain. In the polymerization of a mixture of the endo-/ exo- isomers of 2-methoxycarbonyl-5-norbornene, the endo-isomer was consumed prior to consumption of the exo-isomer, contrary to the well-known tendency in Pd(II)-based catalyst systems. Another notable feature of the present catalytic system was the strong dependency of the molecular weight on the reaction temperature, which was studied in detail for the copolymerization of 2-methoxycarbonyl-5-norbornene with norbornene: we could control the molecular weight without the use of a chain transfer agent. The extracted oligomeric fraction of poly(norbornene) showed the presence of a terminal CC double bond as well as a C 6F 5 unit that was bound to the first norbornane unit in the polymer chain.

ChemInform Abstract: Selective Reduction of 6‐Substituted 1,5‐Dinitro‐3‐azabicyclo[3.3.1]non‐6‐enes.

AbstractReduction of title compound (Ia) with iron, zinc, tin, or with hydrogen over Raney nickel in the case of (Ib) and (Ic) preserves the endocyclic double bond in substrates (I).

Synthesis and Biological Evaluation of Antitumor‐Active Arglabin Derivatives

Arglabin derivatives varied at the endo- or exo-cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line-dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.

ChemInform Abstract: Ring Strain‐Promoted Allylic Transportation of Cyclic Silyl Ethers.

AbstractVarious eight‐membered cyclic siloxadienes are converted to six‐membered siloxenes bearing an endocyclic double bond and an alkenyl substituent.

Addition polymerization of 5-ethylidene-2-norbornene by cationic palladium cationic complex and subsequent derivatization

Poly(5-ethylidene-2-norbornene) (PENB) was synthesized via a vinylic pathway using a cationic palladium-based catalyst, displaying high activity up to 1.06×106g-PENB/mol Pd. The effects of the monomer to catalyst ratio, temperature, reaction time, and concentration on the polymerization were investigated systematically. The control tests and spectroscopic analyses of the PENB indicate that 5-ethylidene-2-norbornene is polymerized via an addition polymerization using endocyclic double bonds. The post-modification was also performed using a free radical graft polymerization. The resulting PENB copolymers were characterized by IR, 1H NMR, and GPC analyses. Open image in new window

Terpene-Based Renewable Monomers and Polymers via Thiol–Ene Additions

Solvent and radical initiator-free addition of thiols to terpenes ((R)-(+)- and (S)-(−)-limonene and (−)-β-pinene) are described as a simple approach to obtain a wide range of alcohol and/or ester functionalized renewable monomers. (R)-(+)-Limonene (1) and (S)-(−)-limonene (2), presenting different reactivity at the endocyclic and exocyclic double bonds, have yielded the monoaddition or diaddition product by simple variation of the thiol feed ratio. In the same manner, (−)-β-pinene (3) derived alcohol and ester monomers have been prepared. The monomers thus obtained have been characterized, and their behavior in polycondensation has been studied. It has been found that long chain diesters or diols, which were synthesized from a castor oil derived platform chemical, are suitable comonomers and result in polycondensates with number-average molecular weights of up to 25 kDa. Thus, terpene/fatty acid-based polyesters were prepared, and their structure–thermal property relationships were studied.

ChemInform Abstract: Unusual (E)‐Selective Ring‐Closing Metathesis to Form Eight‐Membered Rings.

AbstractThe reaction affords siladioxocine derivatives with (Z)‐ or (E)‐geometry at the endocyclic double bond, strongly depending on the sterical and configurational vicinity.

Highly Regioselective Synthesis of Ethyl 2-(N-Methylformate-1,4,5,6-tetrahydropyridin-2-yl) Acetate and Its Conversion into Corresponding (R)-Ethyl Homopepicolate by Asymmetric Hydrogenation

Ethyl 2-(N-methylformate-1,4,5,6-tetrahydropyridin-2-yl) acetate with endocyclic double bond was prepared with high regioselectivity and further reduced into (R)-N-protected homopipecolate with a good enantioselectivity using chiral ruthenium catalyst.

Functionalization of (2S)‐Isopropyl‐5‐iodo‐2,3‐dihydro‐4(H)‐pyrimidin‐4‐ones by a Suzuki–Miyaura Cross‐Coupling Reaction Using Aryltrifluoroborate Salts: Convenient Enantioselective Preparation of α‐Substituted β‐Amino Acids

AbstractA simple protocol for the Pd(OAc)2‐catalyzed cross‐coupling reaction of 1‐benzoyl‐(2S)‐isopropyl‐5‐iodo‐2,3‐dihydro‐4(H)‐pyrimidin‐4‐ones with potassium aryltrifluoroborates was developed. The reaction is performed at 110 °C with a ligand‐free catalyst. In all cases, complete conversion of the 1‐benzoyl‐(2S)‐isopropyl‐5‐iodo‐2,3‐dihydro‐4(H)‐pyrimidin‐4‐onesand aryltrifluoroborates into the C–C coupling products was observed within 30–360 min. It is noteworthy that a largevariety of groups present in the potassium aryltrifluoroborates (–CF3, –OMe, –SEt, –CN, –CHO, –Cl, –Cbz, –NCbz,–OH, –CO2H) could be tolerated. Hydrogenation of the endocyclic double bonds in the Suzuki–Miyaura products followed by acid hydrolysis afforded highly enantioenrichedα‐aryl‐substituted β‐amino acids.

A Concise Total Synthesis of Amphidinolide T2

RCM + AD = T2: In the presence of the C16-methylene group, regioselective ring-closing metathesis (RCM) formed the (12E)-endocyclic double bond, which underwent Os-catalyzed asymmetric dihydroxylation (AD) to give the desired 12,13-diol intermediate required for the total synthesis of amphidinolide T2 in 16 linear steps in 8.0% overall yield.