1-Phosphabicyclo[3,3,1]nonan

1-Phosphabicyclo[3,3,1]nonane The synthesis of 1-phosphabicyclo[3,3,1]nonane II by free-radical cyclization of the primary phosphine (CH₂?CH? CH₂)₂CH? CH? PH₂ I is described. IR data favour a twin-chair conformation of II and its derivatives with oxygen V and sulphur VI . The magnitudes of the ³¹P NMR chemical shifts and of the phosphorus-hydrogen spin-spin coupling constants (¹J_PH, ²J_PH) are compared with values of aliphatic phosphines R₃P. The degree of substitution of CO from Ni(CO)₄ by II and other chemical evidences suggest a TOLMAN ligand cone angle of about 120–125°.     

Synthesis of perfluorobicyclic ethers [2]. The electrochemical fluorination of α-cyclohexenyl-substituted carboxylic acid derivatives

The electrochemical fluorination of α-cyclohexenyl-substituted carboxylic esters [

; R′CH₃, C₂H₅, C₃H₇)] afforded both perfluoro(9-alkyl-7-oxa-bicyclo[4.3.0]nonane)s and perfluoro(8-alkoxy-9-alkyl-7-oxabicyclo[4.3.0]nonane)s in fairly good yields. As the driving force for the ring-closure in this fluorination, a mechanism which involves a resonance stabilized intermediate radical is proposed. Perfluoro(8-chloro-8-methoxy-9-ethyl-7-oxabicyclo[4.3.0]nonane) and perfluoro(8,8-dichloro-9-ethyl-7-oxabicyclo[4.3.0]nonane) were obtained by the controlled chlorination of perfluoro(8-methoxy-9-ethyl-7-oxabicyclo[4.3.0]nonane) with anhydrous aluminum chloride in low yields. Some new fused perfluorobicyclic ethers and a perfluoroacid fluoride obtained in this experiment have been characterized by infrared, mass and ¹⁹F nmr spectra and elemental analysis.     

γ-anti-Effekt an 1-Phosphabicyclo[3.3.1]nonan-Derivaten mit Substituenten am Phosphor. Synthese und Struktur von Pentacarbonyl(1-phosphabicyclo[3.3.1]nonan)chrom

γ-Anti Effect in 1-Phosphabicyclo[3.3.1]nonane Derivatives with Substituents at Phosphorus. Synthesis and Structure of Pentacarbonyl(1-phosphabicyclo[3.3.1]nonane) Chromium In 1-phosphabicyclo[3.3.1]nonane derivatives of the composition C₈H₁₅P(X) the CC-conformation always dominates. Changes in the chemical shifts of the bridge-head carbon atom C(5) in the ¹³C-NMR spectrum are only originated by the electronic influence of the substituent X at the phosphorus centre. Based on a homogeneous interpretation of the electronic interactions and with regard to Pearsons's definition of electronegativity the electronegativities of substituents at the phosphorus atom X = Cr(CO)₅, Fe(CO)₄, and Ni(CO)₃ are estimated. These groups are placed in antiperiplanar orientation to the carbon atom C(5). The molecular structure of (1-phosphabicyclo[3.3.1]-nonane) Cr(CO)₅ 3 was elucidated by X-ray diffraction analysis. The molecule features the 1-phosphabicyclononane ligand in the CC-conformation, which has a nearly undistorted Cr(CO)₅ unit coordinated to the phosphorus atom (d Cr P = 2.368(1) Å).     

The reaction of perfluorobicyclic ethers and perfluorospiro-ethers with anhydrous aluminum chloride

Perfluorobicyclic ethers and perfluorospiroethers, all containing an oxolane skeleton, were treated with AlCl₃ in a heterogeneous manner to give the corresponding α,α,α′-trichlorinated and α,α-dichlorinated products, respectively. From perfluoroacetal compounds, for example, perfluoro(8-methoxy-7-oxabicyclo- [4.3.0]nonane), mono- and di-chlorinated products, i.e. perfluoro- (8-chloro-8-methoxy-7-oxabicyclo[4.3.0]nonane) and perfluoro- (8,8-dichloro-7-oxabicyclo[4.3.0]nonane) were obtained in good yields. The action of fuming sulfuric acid on these polychlorinated products led to the formation of the corresponding lactones. Perfluoro(6-chloro-7-oxa-8-oxobicyclo[4.3.0]nonane) was treated with (CH₃)₂NLi to give N,N-dimethylundecafluoro-2-oxocyclohexyl- acetamide.     

Highly efficient racemisation of a key intermediate of the antibiotic moxifloxacin

N-Chlorination by sodium dichloroisocyanurate and dehydrochlorination by TEA, followed by hydrogenation, allowed (1R,6S)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane to be quantitatively racemised and the resulting trans-free cis racemate to be recycled into the resolution process to yield (1S,6R)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane, a key intermediate of moxifloxacin.     

Development of a novel nucleoside analogue with S-type sugar conformation: 2′-deoxy-trans-3′,4′-bridged nucleic acids

Two novel trans-3′,4′-bridged nucleic acid (trans-3′,4′-BNA) monomers, one with a 3,5,8-trioxabicyclo[5.3.0]decane structure and the other with a 4,7-dioxabicyclo[4.3.0]nonane structure, were successfully synthesized from thymidine. The locked trans-fused ring structures of the nucleoside analogues were confirmed by X-ray crystallography, which also indicated that their furanose rings had a typical S-type conformation involving C_2′-endo or C_3′-exo sugar puckering, respectively, and the same ring conformation as that observed in the B-type helical structure of the DNA duplex.     

Rate constants for the gas-phase reactions of OH radicals with a series of bi- and tricycloalkanes at 299 ± 2 K: Effects of ring strain

Relative rate constants for the gas-phase reactions of OH radicals with a series of bi- and tricyclic alkanes have been determined at 299 ± 2 K, using methyl nitrite photolysis in air as a source of OH radicals. Using a rate constant for the reaction of OH radicals with cyclohexane of 7.57 × 10^?12 cm³/molec·s, the rate constants obtained are (× 10¹² cm³/molec·s): bicyclo[2.2.1]heptane, 5.53 ± 0.15; bicyclo[2.2.2]octane, 14.8 ± 1.0; bicyclo[3.3.0]octane, 11.1 ± 0.6; cis-bicyclo[4.3.0]nonane, 17.3 ± 1.3; trans-bicyclo[4.3.0]nonane, 17.8 ± 1.3; cis-bicyclo[4.4.0]decane, 20.1 ± 1.4; trans-bicyclo[4.4.0]decane, 20.6 ± 1.2; tricyclo[5.2.1.0^2,6]decane, 11.4 ± 0.4; and tricyclo[3.3.1.1^3,7]decane, 23.2 ± 2.1. These data show that overall ring strain energies of ?4–5 kcal mol^?1 have no significant effect on the rate constants, but that larger ring strain results in the rate constants being decreased, relative to those expected for the strain-free molecules, by ratios which increase approximately exponentially with the overall ring strain.     

1,5-Diphosphabicyclo[3.3.1]nonan

1,5-Diphosphabicyclo [3.3.1]nonane 1,5-Diphosphabicyclo[3.3.1]nonane 8 has been obtained by free-radical cyclization of CH₂?CHCH₂(H)PCH₂P(H)CH₂CH?CH₂ 6 and 1-allyl-1,3-diphosphorinane 7 . For the synthesis of 6 and 7 the chlorophosphine Cl₂PCH₂PCl₂ 1 is used as a starting material, which can be converted into Me₂N(Cl)PCH₂P(Cl)NMe₂ 3 by reaction with (Me₂N)₂PCH₂P(NMe₂)₂ 2 . Treatment of 3 with two equivalents of allyl lithium and cleavage of the PN bonds in CH₂?CHCH₂(Me₂N)PCH₂P(NMe₂)CH₂CH?CH₂ 4 with diluted HCl affords CH₂?CHCH₂(H)(O)PCH₂P(O)(H)CH₂CH?CH₂ 5 . Phenylsilane is used for the first time as a reducing agent to obtain a secundary phosphine like 6 from the secundary phosphine oxide ( 5 ). Prolonged heating increases the yield of the byproduct 7 in the mixture of 6 and 7 . Reactions of the trivalent phosphorus in 8 with CS₂, CH₃I, POCl₃, NO, sulfur, and KSeCN, respectively, delivers the corresponding derivatives 9–17 . The compounds decribed are characterized by ¹H, ¹³C, ³¹P, ⁷⁷Se n.m.r., i.r., and m.s. data.     

The first total synthesis of acutifolone A, a pinguisane-type sesquiterpenoid isolated from the Japanese liverwort Porella acutifolia subsp. tosana

The first total synthesis of acutifolone A, a sesquiterpenoid carrying the bicyclo[4.3.0]nonane structure 1, was successfully achieved from the intermediate 6 produced by the intramolecular Diels-Alder reaction.     

Synthesis of 6,7-benzo-3-borabicyclo[3.3.1]nonane and its 3-aza analog from 2-allylphenyl(diallyl)borane. Intramolecular arylboration of the C=C bond

A method was developed for the synthesis of 6,7-benzo-3-borabicyclo[3.3.1]nonane and 6,7-benzo-3-azabicyclo[3.3.1]nonane derivatives based on intramolecular cyclization of 2-allylphenyl(diallyl)borane. Intramolecular arylboration of the double bond in 1,5-diallyl-2,3-benzo-1-boracyclohexane was carried out for the first time. Conventional oxidation (H₂O₂-OH⁻) of 6,7-benzo-3-methoxy-3-borabicyclo[3.3.1]nonane afforded cis-1,3-di(hydroxymethyl) tetralin. The structure of the latter was established by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 668–672, March, 2005.     

Preparative and NMR studies of 1,3-dienecobalt(I) complexes

The synthesis and the characterization of cobalt(I) complexes of the type [Co(diene)(phosphine)₃]Y (diene = 1,3-butadiene and isoprene; phosphine = PMe₃, PMe₂Ph, and HPPh₂; Y = ClO₄, BF₄, or BPh₄) are reported. The fluxional nature of the five-coordinate cations [Co(diene)(phosphine)₃]⁺ is shown by variable-temperature NMR spectroscopy (¹H and ³¹P). Low-temperature spectra are consistent with a square-pyramidal structure in which the diene occupies two basal coordination sites.     

Synthesis and reactivity of cyclo-tetra(stibinophosphonium) tetracations: redox and coordination chemistry of phosphine–antimony complexes

Reductive elimination of [R₃PPR₃]²⁺, [11(R)]²⁺, from the highly electrophilic Sb^III centres in [(R₃P)₃Sb]³⁺, [8(R)]³⁺, gives Sb^I containing cations [(R₃P)Sb]¹⁺, [9(R)]¹⁺, which assemble into frameworks identified as cyclo-tetra(stibinophosphonium) tetracations, [(R₃P)₄Sb₄]⁴⁺, [10(R)]⁴⁺. A phosphine catalyzed mechanism is proposed for conversion of fluoroantimony complexes [(R₃P)₂SbF]²⁺, [7(R)]²⁺, to [10(R)]⁴⁺, and the characterization of key intermediates is presented. The results constitute evidence of a novel ligand activation pathway for phosphines in the coordination sphere of hard, electron deficient acceptors. Characterization of the associated reactants and products supports earlier, albeit less definitive, detection of analogous phosphine ligand activation in Cu^III and Tl^III complexes, demonstrating that these prototypical ligands can behave simultaneously as reducing agents and σ donors towards a variety of hard acceptors. The reactivity of the parent cyclo-tetra(stibinophosphonium) tetracation, [10(Me)]⁴⁺, is directed by high charge concentration and strong polarization of the P–Sb bonds. The former explains the observed facility for reductive elimination to yield elemental antimony and the latter enabled activation of P–Cl and P–H bonds to give phosphinophosphonium cations, [Me₃PPR′2]¹⁺, including the first example of an H-phosphinophosphonium, [(Me₃P)P(H)R′]¹⁺, and 2-phosphino-1,3-diphosphonium cations, [(Me₃P)₂PR′]²⁺. Exchange of a phosphine ligand in [10(Me)]⁴⁺ with [nacnac]^1– gives [(Me₃P)₃Sb₄(nacnac)]³⁺, [15(Me)]³⁺, and with dmap gives [(Me₃P)₃Sb₄(dmap)]⁴⁺, [16]⁴⁺. The lability of P–Sb or Sb–Sb interactions in [10(Me)]⁴⁺ has also been illustrated by characterization of heteroleptically substituted derivatives featuring PMe₃ and PEt₃ ligands.     

An Efficient Synthesis of 2,8-Diazabicyclo[4.3.0]-nonane Derivatives via Intramolecular Cyclization Reaction

Novel 5-functionalized-2,8-diazabicyclo[4.3.0]nonane derivatives 5 were synthesized from epoxide 1 through 4 steps in 46.7～52.6% yield.     

Synthesis of neodysiherbaine

The stereocontrolled synthesis of neodysiherbaine from diacetyl-l-arabinal is described. Key steps in the synthesis include the use of an asymmetric phase-transfer catalyzed glycine imine alkylation to introduce the α-amino acid function, and the RuO₄-mediated oxidative cyclization of a 1,5-diene to generate the 2,7-dioxabicyclo[4.3.0]nonane ring system.     

Scope and applications of second generation palladium-catalyzed cycloalkenylation. Stereoselective total syntheses of isoiridomyrmecin, isodihydronepetalactone, and α-skytanthine

Functionalized bicyclo[3.2.1]octanes, -oxabicyclo-[4.3.0]nonanes, 3-azabicyclo[3.3.0]octanes, and 3-azabicyclo[4.3.0]nonanes were easily synthesized via a second generation palladium-catalyzed cycloalkenylation. Isoiridomyrmecin and isodihydronepetalactone, both of which feature a 3-oxabicyclo[4.3.0]nonane subunit, were stereoselectively synthesized via a second generation palladium-catalyzed cycloalkenylation as the key step. α-Skytanthine, a typical 3-azabicyclo[4.3.0]nonane alkaloid, was also constructed using the same catalytic cyclization protocol.     

Oxidative and hydrolytic cleavage of cyclopropane and spirocyclobutane derivatives of 6,8-dioxabicyclo[3.2.1]octane,the products of transformation of levoglucosenone

A new method for the synthesis of (1R,4S,5S)-4-hydroxymethyl-3-oxabicyclo[3.1.0]hexan2-one, the cyclopropane analog of (S)-5-hydroxypent-2-en-4-olide, has been suggested based on oxidation of (1S,2S,4R,6R)-7,9-dioxatricyclo[4.2.1.0^2,4]nonan-5-one. Oxidation of cyclobutanones, spirojoined with the fragments of 6,8-dioxabicyclo[3.2.1]oct-2-ene, 6,8-dioxabicyclo[3.2.1]octane (at position 4), or 7,9-dioxatricyclo[4.2.1.0^2,4]nonane (at position 5), upon the action of m-chloroperoxybenzoic acid or the KMnO₄-H₂SO₄-H₂O system leads to the corresponding spirojoined butanolides in 73–85% yields. The same cyclobutanones easily undergo the four-membered ring opening upon the action of dilute H₂SO₄ at 50–90 °C to form 6,8-dioxabicyclo[3.2.1]octane-4- or 7,9-dioxatricyclo[4.2.1.0^2,4]nonane-5-propionic acid.     

Cis- und trans-1-Phosphabicyclo[4.4.0]decan

Cis- and trans-1-Phosphabicyclo[4.4.0]decane A mixture of cis-( 5a ) and trans-1-phosphabicyclo [4.4.0] decane 5b has been prepared by free-radical cyclization of (CH₂ = CH? CH₂? CH₂)₂CH? PH₂ 10 . The isomers could be separated in a pure state. Stereostructures have been assigned by ¹³C n.m.r. at 153—302 K. Equilibration of 5a and 5b by u.v. irradiation gave ?G°₃₅ ≈? 0 kJ ° mol^?1 · Activation parameters for ring inversion of “cis” stereoisomer 5a and its “cis” P-sulfid 17a are found to be ΔG° = 41.9 kJ · mol^?1 and 39.7 kJ · mol^?1, respectively. Treatment of 5a and 5b with H₂O₂, sulfur, selenium, HSO₃F, CH₃I, CS₂, and Ni(CO)₄, respectively, yield the corresponding derivatives. ¹H, ¹³C, ³¹P, ⁷⁷Se n.m.r. and i.r. data are reported.     

Interaction of PH3 with acetaldehyde in aqueous media and chemistry of [HO(Me)CH]4PCl

The known phosphonium chloride [HO(Me)CH]₄PCl was prepared at ambient conditions from PH₃ and acetaldehyde in aqueous HCl, and characterized by elemental analysis and ¹H and ³¹{¹H} NMR spectroscopy. Attempts to obtain the tertiary phosphine [HO(Me)CH]₃P via reaction of [HO(Me)CH]₄PCl with Na₂SO₃ or Et₃N in aqueous media under Ar revealed that [HO(Me)CH]₃P is unstable and equilibrates with the secondary phosphine [HO(Me)CH]₂PH and acetaldehyde. A 1:4 reaction of [HO(Me)CH]₄PCl with NaHSO₃ at room temperature under Ar affords first the oxide [HO(Me)CH]₂P(O)H and then the phosphinic acid [HO(Me)CH]₂P(O)OH. A 1:1 reaction of [HO(Me)CH]₄PCl with Na₂S₂O₃ affords the sulfide [HO(Me)CH]₃PS. ³¹{¹H} and ¹H NMR data for all the (α-hydroxyethyl)phosphorus species are reported for the first time.     

A short approach to the bicyclo[4.3.0]nonane fragment of stawamycin

The bicyclo[4.3.0]nonane (C₁₁-C₂₁) fragment of stawamycin has been prepared by a sequence involving 11 steps (10% overall yield) from methyl (R)-(−)-3-hydroxy-2-methylpropionate. Key steps are a Pd-catalysed Stille coupling reaction between a vinyl iodide and a vinyl stannane followed by an intramolecular Diels-Alder cycloaddition reaction to give the desired adduct as the major isomer in 21% overall yield.     

Synthesis of 2,6-dioxatricyclo[3.3.1.0]nonanes by intramolecular haloetherification and/or transannular hydroxycyclization of alkenes in [4+3]-cycloadducts

The synthesis of new difunctionalized 2,6-dioxatricyclo[3.3.1.0^3,7]nonanes is described. This type of structure is an interesting synthetic building block for potential bioactive molecules and it was prepared from 8-oxabicyclo[3.2.1]oct-6-en-3-one having a NHBoc function on C-1. This precursor was obtained by a [4+3] cycloaddition reaction of 2-tert-butoxycarbonylaminofuran and the oxyallyl cation generated in situ from 2,4-dibromo-3-pentanone. Reduction of the carbonyl group at C-3 was accomplished in high yield and stereoselective manner to afford the corresponding axial alcohol at C-3 as a major product. Further intramolecular haloetherification of this type of alcohols with NBS and I(py)2BF₄ led to the corresponding bromo and iodo-derivatives at C-8 of the 2,6-dioxatricyclo[3.3.1.0^3,7]nonane framework, in high yield. Epoxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-ol followed by treatment with NaCN, NaN₃, and/or NaOH in MeOH afforded 8-hydroxy-2,6-dioxatricyclo[3.3.1.0^3,7]nonanes in high yield via a transannular hydroxycyclization mediated by a base and through an alkoxide intermediate. The new 2,6-dioxatricyclo[3.3.1.0^3,7]nonanes were tested for biological activity against HIV-1 virus and MT-4 lymphoid cell line, showing a low anti-HIV activity and a high degree of cytotoxicity.