A Novel Tandem Cyclization of 2,7- or 2,8-Bis-Unsaturated Esters Mediated by (η²-Propene)TiX₂ (X = Cl or O-<i>i</i>-Pr). A Facile Construction of Bicyclo[3.3.0]octane, -[4.3.0]nonane, and -[3.1.0]hexane Skeletons

A Novel Tandem Cyclization of 2,7- or 2,8-Bis-Unsaturated Esters Mediated by (η2-Propene)TiX2 (X = Cl or O-i-Pr). A Facile Construction of Bicyclo[3.3.0]octane, -[4.3.0]nonane, and -[3.1.0]hexane Skeleton

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-<i>i</i>-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of <i>d</i>-Sabinene

tert-Butyl 2-en-7-ynoate 6 was treated with (η2-propene)Ti(O-i-Pr)2 (3), generated in situ from Ti(O-i-Pr)4 or Ti(O-i-Pr)3Cl and i-PrMgCl, in ether at −50 to −20 °C to afford the product 8 in good yield. The presence of the intermediate titanabicycle 7 was verified by bis-deuterolysis with excess D2O. When the titanabicycle 7 was treated with 1.1 equiv of i-PrOD and then worked up as usual, the monodeuterated product 10 was obtained with high site selectivity and stereoselectivity. Other electrophiles such as aldehydes and ketones also reacted with the titanabicycle in a highly stereoselective manner to give cyclopentanes having a stereo-defined side chain. On the contrary, treatment of the corresponding ethyl ester, ethyl 8-(trimethylsilyl)-(E)-2-octen-7-ynoate (28), with 3 under the same conditions followed by the addition of 1.1 equiv of s-BuOH afforded 2-(trimethylsilyl)-1-bicyclo[3.3.0]octen-3-one (32) in 80% yield. Quenching the same reaction mixture with i-PrOD, EtCHO, and Et2CO in place of s-BuOH gave 4-deuterio (with exclusive deuterium incorporation), 4-(1-hydroxypropyl), and 4-(1-ethyl-1-hydroxypropyl) derivatives of the above bicyclic ketone (34, 35, and 36) in good yields. These electrophiles were always introduced from the convex face of the bicyclic skeleton. The stereochemistry of the cyclization could be controlled by an allylic substituent such as (tert-butyl)dimethylsiloxy or butyl group to a high degree yet with a reversal diastereoselection to give 45 or 47. The reaction of ethyl 7-octen-2-ynoate (56) and 3 at −50 to 0 °C took place in a quite different way to afford 1-[(ethoxycarbonyl)methyl]bicyclo[3.1.0]hexane (64) in 74% yield after hydrolysis. If the simple hydrolysis is replaced by deuterolysis or the action of diethyl ketone, 1-[(ethoxycarbonyl)dideuteriomethyl] (with 99% deuterium incorporation), or 1-[(ethoxycarbonyl)(3-pentylidene)methyl] derivative of the above product (65 or 66) was obtained in good yields. A 7-en-2-ynoate having an internal Z-double bond such as 80 afforded a single stereoisomer 82 with the substituent at the endo position of the bicyclic skeleton, suggesting that the stereochemical integrity of the Z-double bond of the starting material was retained in the product. An alkyl substituent at the allylic position of the substrates like 74 and 76 nicely controlled the stereochemistry of the cyclization to afford single products 75 and 77 with the substituent being placed in the exo orientation of the bicyclic structure. This high diastereoselectivity was successfully applied to an enantioselective synthesis of d-sabinene from an optically active enynoate via nearly complete chirality transfer

Lithium Chloride: An Active and Simple Catalyst for Cyanosilylation of Aldehydes and Ketones

LiCl acts as a highly effective catalyst for cyanosilylation of various aldehydes and ketones to the corresponding silylated cyanohydrins. The reaction proceeds smoothly with a substrate/catalyst molar ratio of 100−100 000 at 20−25 °C under solvent-free conditions. α,β-Unsaturated aldehydes are completely converted to the 1,2-adducts. The cyanation products can be isolated by direct distillation of the reaction mixture

Oxidation of Primary Amines to Oximes with Molecular Oxygen using 1,1-Diphenyl-2-picrylhydrazyl and WO₃/Al₂O₃ as Catalysts

The oxidative transformation of primary amines to their corresponding oximes proceeds with high efficiency under molecular oxygen diluted with molecular nitrogen (O₂/N₂ = 7/93 v/v, 5 MPa) in the presence of the catalysts 1,1-diphenyl-2-picrylhydrazyl (DPPH) and tungusten oxide/alumina (WO₃/Al₂O₃). The method is environmentally benign, because the reaction requires only molecular oxygen as the terminal oxidant and gives water as a side product. Various alicyclic amines and aliphatic amines can be converted to their corresponding oximes in excellent yields. It is noteworthy that the oxidative transformation of primary amines proceeds chemoselectively in the presence of other functional groups. The key step of the present oxidation is a fast electron transfer from the primary amine to DPPH followed by proton transfer to give the α-aminoalkyl radical intermediate, which undergoes reaction with molecular oxygen and hydrogen abstraction to give α-aminoalkyl hydroperoxide. Subsequent reaction of the peroxide with WO₃/Al₂O₃ gives oximes. The aerobic oxidation of secondary amines gives the corresponding nitrones. Aerobic oxidative transformation of cyclohexylamines to cyclohexanone oximes is important as a method for industrial production of ε-caprolactam, a raw material for Nylon 6

Ring-Opening Polymerization of THF by Aryloxo-Modified (Imido)vanadium(V)-alkyl Complexes and Ring-Opening Metathesis Polymerization by Highly Active V(CHSiMe₃)(NAd)(OC₆F₅)(PMe₃)₂

Ring-opening polymerizations of THF using V­(NR)­(CH₂SiMe₃)­(OAr)₂ [R = 2,6-Me₂C₆H₃, 1-adamantyl (Ad), Ph; Ar = 2,6-Me₂C₆H₃, C₆F₅] proceeded in a living manner in the presence of [Ph₃C]­[B­(C₆F₅)₄], affording high molecular weight polymers with low PDI (<i>M</i>_w/<i>M</i>_n) values: the observed activity (initiation efficiency) was affected by the arylimido and aryloxo ligands employed. A new vanadium­(V)-alkylidene, V­(CHSiMe₃)­(NAd)­(OC₆F₅)­(PMe₃)₂, prepared from V­(NAd)­(CH₂SiMe₃)₂(OC₆F₅) by α-hydrogen elimination in <i>n</i>-hexane in the presence of PMe₃ at 25 °C, exhibited remarkable catalytic activity for ring-opening metathesis polymerization of norbornene: the activity at 25 °C was higher than those by the reported vanadium­(V)-alkylidenes and ordinary Mo­(CHCMe₂Ph)­(N-2,6-^<i>i</i>Pr₂-C₆H₃)­(O^<i>t</i>Bu)₂

Ring-Opening Polymerization of THF by Aryloxo-Modified (Imido)vanadium(V)-alkyl Complexes and Ring-Opening Metathesis Polymerization by Highly Active V(CHSiMe₃)(NAd)(OC₆F₅)(PMe₃)₂

Ring-opening polymerizations of THF using V­(NR)­(CH2SiMe3)­(OAr)2 [R = 2,6-Me2C6H3, 1-adamantyl (Ad), Ph; Ar = 2,6-Me2C6H3, C6F5] proceeded in a living manner in the presence of [Ph3C]­[B­(C6F5)4], affording high molecular weight polymers with low PDI (Mw/Mn) values: the observed activity (initiation efficiency) was affected by the arylimido and aryloxo ligands employed. A new vanadium­(V)-alkylidene, V­(CHSiMe3)­(NAd)­(OC6F5)­(PMe3)2, prepared from V­(NAd)­(CH2SiMe3)2(OC6F5) by α-hydrogen elimination in n-hexane in the presence of PMe3 at 25 °C, exhibited remarkable catalytic activity for ring-opening metathesis polymerization of norbornene: the activity at 25 °C was higher than those by the reported vanadium­(V)-alkylidenes and ordinary Mo­(CHCMe2Ph)­(N-2,6-iPr2-C6H3)­(OtBu)2

Aerobic Oxidative Esterification of Aldehydes with Alcohols by Gold–Nickel Oxide Nanoparticle Catalysts with a Core–Shell Structure

Oxidative esterification of aldehydes with alcohols proceeds with high efficiency in the presence of molecular oxygen on supported gold–nickel oxide (AuNiO_<i>x</i>) nanoparticle catalysts. The method is environmentally benign because it requires only molecular oxygen as the terminal oxidant and gives water as the side product. The AuNiO_<i>x</i> nanoparticles have a core–shell structure, with the Au nanoparticles at the core and the surface covered by highly oxidized NiO_<i>x</i>. Aerobic oxidative esterification of methacrolein in methanol to methyl methacrylate is an important industrial method for the production of polymethyl methacrylate

Abolished BMC transplantation-induced cardiac function recovery by HMGB1-inhibition.

<p>Cardiac parameters were measured by echocardiography (<b>A–D</b>) and catheterization (<b>E–H</b>) on day 28 after each treatment. Cardiac function was improved by BMC transplantation (BMC group) compared to the PBS injection control (CON group), while this effect was eliminated by antibody neutralization of HMGB1 (AB group), but not by control IgG administration (IgG group). LVFAC, left ventricular fractional area change; ECA, endocardial area. *:<i>p</i><0.05 <i>versus</i> the CON group, ^†:<i>p</i><0.05 <i>versus</i> the BMC group. ^‡:<i>p</i><0.05 <i>versus</i> the IgG group, mean±SEM for n = 8∼10 in each group.</p

Histological findings of BMMNC retention 5 min after IC injection.

Recipient hearts were collected at 5 minutes after IC injection of 8x106 BMMNC that had been labeled with PKH67. A and B represent low- and high-magnification images of Isolectin-B4 staining, respectively (scale bar = 100 μm [A] and 30 μm [B]). Representative micro images from n = 4 hearts are presented. All donor BMMNC (green) retained in the heart were found to be entrapped in isolation and within the coronary microvasculature. Blue signals for nuclei (DAPI); red for endothelial cells (Isolectin-B4).</p

Eliminated BMC transplantation-induced tissue recovery by HMGB1-inhibition.

<p>Reduced extracellular collagen deposition (<b>A–C;</b> picrosirius red = red), increased capillary density (<b>D–F;</b> Isolectin B4 = red), and increased proliferation (<b>G–I;</b> Ki67 = red; nuclei = blue; cTnT = green) were observed in the border areas at day 28 after BMC transplantation (BMC group), compared to the PBS control (CON group). These effects were all abolished by anti-HMGB1 antibody neutralization (AB group), but not by control IgG administration (IgG group). Representative images of only BMC and AB groups are present (see <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076908#pone.0076908.s002" target="_blank">Figure S2</a></b> for additional images). Scale bars = 50 µm in <b>A, B, G, H</b> and 30 µm in <b>D, E</b>. *:<i>p</i><0.05 <i>versus</i> the CON group, ^†:<i>p</i><0.05 <i>versus</i> the BMC group, ^‡:<i>p</i><0.05 <i>versus</i> the IgG group, mean±SEM for n = 5∼7 in each group.</p