Synthesis of 2-azabicyclo[2.1.0]pentanes by the intramolecular nucleophilic substitution of cyclopropylmagnesium carbenoids with magnesium anilide

A variety of 2-azabicyclo[2.1.0]pentanes were synthesized by the intramolecular nucleophilic substitution of cyclopropylmagnesium carbenoids with magnesium anilide. The 1-chlorocyclopropyl p-tolyl sulfoxides possessing an N-aryl-substituted aminomethyl group were prepared from dichloromethyl p-tolyl sulfoxide, α,β-unsaturated carboxylic acid esters, and anilines in four steps. The deprotonation of the amine with t-BuMgCl followed by sulfoxide/magnesium exchange of the sulfoxides with i-PrMgCl led to the generation of the cyclopropylmagnesium carbenoids possessing a magnesium anilide moiety. Subsequent intramolecular nucleophilic substitution of the cyclopropylmagnesium carbenoids occurred in a 4-exo-tet manner to give the 2-azabicyclo[2.1.0]pentanes. The optically active 2-azabicyclo[2.1.0]pentane was synthesized using a p-tolylsulfinyl group as a chiral auxiliary.     

Synthesis, Characterization, and Crystal Structure of a (&mgr;-Oxo)bis(&mgr;-acetato)diiron(III) Complex with a Dinucleating Hexapyridine Ligand, 1,2-Bis[2-(bis(2-pyridyl)methyl)-6-pyridyl]ethane. The First Example of a Discrete (&mgr;-Oxo)bis(&mgr;-acetato)diiron(III) Complex with a Dinucleating Ligand

A mononucleating tripyridine ligand, 2-(bis(2-pyridyl)methyl)-6-methylpyridine (L(1)), and a dinucleating hexapyridine ligand, 1,2-bis[2-(bis(2-pyridyl)methyl)-6-pyridyl]ethane (L(2)), have been prepared. The reaction of a carbanion of 2,6-lutidine with 2-bromopyridine affords L(1) which is converted to L(2) quantitatively by treating with tert-butyllithium and 1,2-dibromoethane. (&mgr;-Oxo)bis(&mgr;-acetato)diiron(III) complexes [Fe(2)(O)(OAc)(2)(L(1))(2)](ClO(4))(2) (1) and [Fe(2)(O)(OAc)(2)L(2)](ClO(4))(2) (2) have been synthesized and characterized by means of infrared, UV/vis, mass, and M?ssbauer spectroscopies and by measuring magnetic susceptibility and cyclic voltammograms. All the spectral data are consistent with the (&mgr;-oxo)bis(&mgr;-acetato)diiron(III) core structure in both 1 and 2. A relatively strong molecular ion peak at m/z 865 corresponding to [{Fe(2)O(OAc)(2)L(2)}(ClO(4))](+) in a FAB mass spectrum of 2 suggests the stabilization of the (&mgr;-oxo)bis(&mgr;-acetato)diiron(III) core structure by L(2) in a solution state. The compound 2.DMF.2-PrOH.H(2)O, chemical formula C(44)Cl(2)Fe(2)H(51)N(7)O(16), crystallizes in the monoclinic space group C2/c with a = 22.034(6) ?, b = 12.595(5) ?, c = 20.651(7) ?, beta = 121.49(2) degrees, and Z = 4. The cation has 2-fold symmetry with the bridging oxygen atom on the 2-fold axis: Fe-(&mgr;-O) = 1.782(5) ?, Fe-O-Fe = 123.6(6) degrees, and Fe.Fe = 3.142(3) ?. The diiron(III) core structure of 2 seems to be stabilized by encapsulation of the ligand. Compound 2 is the first example of a discrete (&mgr;-oxo)bis(&mgr;-acetato)diiron(III) complex with a dinucleating ligand.     

Dependence of the Reactivities of Titanium Enolates on How They Are Generated: Diastereoselective Coupling of Phenylacetic Acid Esters Using Titanium Tetrachloride

Oxidative coupling of phenylacetic acid esters was easily achieved by treating the esters with TiCl(4) and then adding Et(3)N to the resulting solution. The products consisted of dl- and meso-2,3-diphenylsuccinic acid esters with the Claisen condensation product, and the ratio of these products depended on the reaction conditions. Reaction conditions suitable for high dl selectivity were determined, and a dimer of titanium enolate was postulated as an intermediate responsible for the high dl selectivity. The selectivities were compared with those in known oxidative couplings in which titanium enolate intermediates are prepared through lithium enolates and silyl enol ethers. The results suggest that the reactivities of titanium enolates intermediates depend on how they are generated.     

Linear polybiurets: Facile synthesis and characteristic properties

Linear polybiurets have been synthesized by polyaddition of benzyloxyamine and diisocyanates, and properties of the novel polymeric materials have been elucidated. Prior to polymerization, model reactions between benzyloxyamine and phenyl isocyanate were examined in detail and proved to be controlled by the molar ratio of reagents and by catalysts to give the urea (1:1 adduct) and/or biuret (1:2 adduct). Under appropriate conditions, the biuret was synthesized in a quantitative yield. Polymerization of equimolar amounts of benzyloxyamine and diphenylmethane or hexamethylene diisocyanate proceeded smoothly to give polybiurets with inherent viscosities up to 0.52 dL/g. The benzyl group of the model biuret and polybiuret could be removed by catalytic hydrogenation. Both the N-benzyloxy-type and N-hydroxy-type polybiurets showed excellent solubility in common organic solvents. The two kinds of polybiurets as well as model biurets adsorbed metal cations efficiently. The N-hydroxybiuret structure exhibited particularly high affinity for iron(III) and was useful for selective removal of iron from metal cation mixtures. © 1996 John Wiley & Sons, Inc.     

Synthesis and polymerization of N‐(4‐tetrahydropyranyl‐oxyphenyl)maleimide

N‐(4‐Tetrahydropyranyl‐oxy‐phenyl)maleimide (THPMI) was prepared and polymerized by radical or anionic initiators. THPMI could be polymerized by 2,2′‐azobis(isobutyronitrile) (AIBN) and potassium tert‐butoxide. Radical polymers (poly(THPMI)r) were obtained in 15–50% yields for AIBN in THF at 65°C after 2–5 h. The yield of anionic polymers (poly(THPMI)a) obtained from potassium tert‐butoxide in THF at 0°C after 20 h was 91%. The molecular weights of poly(THPMI)r and poly(THPMI)a were M_n = 2750–3300 (M_w/M_n = 1.2–3.3) and M_n = 11300 (M_w/M_n = 6.0), respectively. The difference in molecular weights of the polymers was due to the differences in the termination mechanism of polymerization and the solubility of these polymers in THF. The thermal decomposition temperatures were 205 and 365°C. The first decomposition step was based on elimination of the tetrahydropyranyl group from the poly(THPMI). Positive image patterns were obtained by chemical amplification of positive photoresist composed of poly(THPMI) and 4‐morpholinophenyl diazonium trifluoromethanesulfonate used as an acid generator. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 341–347, 1999     

Pentamethylcyclopentadienylrhodium(III) and -iridium(III) Complexes Showing P,O Coordination: Unprecedented Insertion of tcne and tcnq into a C−H Bond

Strongly electron withdrawing cyanoolefins tetracyanoethylene (tcne) and 7,7,8,8-tetracyano-p-quinodimethane (tcnq) react with [(η⁵-C₅Me₅)MCl(MDMPP-P,O)] (M=Rh, Ir; MDMPP-P,O=PPh₂(2-O-6-MeO-C₆H₃), a P,O chelating phosphane) by insertion into the C−H bond adjacent to the M−O σ bond. The crystal structure of the iridium complex formed upon insertion of tcne is shown.     

Author Index

Authors Index

Author Index     

High-performance liquid chromatographic assay for glucuronidation activity of 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), in human liver microsomes

A simple and sensitive assay for glucuronidation activity of 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), in human liver microsomes by high-performance liquid chromatography (HPLC) with fluorescence detection is reported. The method was validated for the determination of SN-38 glucuronide (SN-38G) with respect to specificity, linearity, recovery, stability, precision, accuracy, and limits of detection and quantitation. There was no interference from matrix and non-enzymatic reactions. The calibration curve for SN-38G was linear from 5 to 500 nM. Average recoveries ranged from 98 to 100% in spiked human liver microsome samples, and the SN-38G was stable at 4 degrees C for at least 72 h. The newly developed method was found to be more sensitive and selective than previous methods using thin layer chromatography and HPLC. The limit of quantitation for SN-38G was 5 nM (2.5 pmol/assay). The intra- and inter-day precision and accuracy were less than 7 and 4%, respectively. The intra- and inter-day precision of enzyme assay for UDP-glucuronosyltransferase (UGT) activity toward SN-38 in human liver microsomes was less than 4%. With this improved sensitivity, the kinetics of SN-38 glucuronidation in human liver microsomes could be determined more precisely. Therefore, this method is applicable to in vitro study on the side effects and drug interactions of CPT-11 using small amounts of biological sample.     

The practical synthesis of a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246)

The synthetic route for a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.