Synthesis of highly enantioenriched all-carbon quaternary centers: conjugate additions of chiral organolithium nucleophiles to alpha,alpha-dinitrile beta,beta-disubstituted olefins

[reaction: see text]. Highly enantioenriched quaternary centers are obtained by the reaction of chiral lithiated intermediates complexed to (-)-sparteine with tetrasubstituted, alpha,alpha-dinitrile activated olefins. Lithiated N-Boc-N-Aryl benzylamine furnishes products with drs from 78:22 to 95:5, with ers exceeding 94:6. Lithiated N-Boc-N-Aryl allylamine reactants provide enecarbamate products with drs from 55:45 to 99:1, with ers ranging from 87:13 to 97:3.     

Closer asymptotic approximations for the distributions of the power divergence goodness-of-fit statistics

Summary The members of the power divergence family of statistics all have an asymptotically equivalent χ² distribution (Cressie and Read [1]). An asymptotic expansion for the distribution function is derived which shows that the speed of convergence to this asymptotic limit is dependent on λ. Known results for Pearson'sX ² statistic and the log-likelihood ratio statistic then appear as special cases in a continuum rather than as separate (unrelated) expansions.     

Detection of trace levels of thiodiglycol in blood, plasma and urine using gas chromatography-electron-capture negative-ion chemical ionisation mass spectrometry

A sensitive method has been developed for the detection and quantitative determination of thiodiglycol in blood, plasma and urine. Samples were extracted from Clin Elut columns and cleaned up on C18 Sep-Pak cartridges (blood, plasma) or Florisil Sep-Pak cartridges (urine). Tetradeuterothiodiglycol was added to the sample prior to extraction as internal standard. Thiodiglycol was converted to its bis-(pentafluorobenzoate) derivative and analysed by capillary gas chromatography-electron-capture negative-ion chemical ionisation mass spectrometry using selected ion monitoring. Levels of thiodiglycol down to 1 ng/ml (1 ppb) could be detected in 1-ml spiked blood and urine samples; calibration curves were linear over the range 5- or 10-100 ng/ml. Blood and urine samples from a number of control subjects were analysed for background levels of thiodiglycol. Concentrations up to 16 ng/ml were found in blood, but urine levels were below 1 ng/ml.     

Use of U-shaped donor-bridge-acceptor molecules to study electron tunneling through nonbonded contacts

A systematic determination of electronic coupling matrix elements in U-shaped molecules is demonstrated. The unique architecture of these systems allows for the determination of the electronic coupling through a pendant molecular moiety that resides between the donor and acceptor groups; this moiety quantifies the efficiency of electron tunneling through nonbonded contacts. Experimental electron-transfer rate constants and reaction free energies are used to calibrate a molecular-based model that describes the solvation energy. This approach makes it possible to experimentally determine electronic couplings and compare them with computational values.     

Asymmetric lithiation-substitution sequences of substituted allylamines

[reaction: see text] (-)-Sparteine-mediated asymmetric lithiation-substitution sequences of 2- and 3-substituted N-(Boc)-N-(p-methoxyphenyl) allylic amines with electrophiles have been investigated. Asymmetric lithiation-substitutions of N-(Boc)-N-(p-methoxyphenyl) allylic amines 11, 12, 13, 14, and 15 provide highly enantioenriched enecarbamates in good yields. Further transformations to give aldehydes, acids, ketones, and a Diels-Alder adduct are reported. The 1,4-addition products from reactions of the lithiated allylic amines from 14 and 15 with conjugated activated alkenes gives enecarbamates with two and three stereogenic centers in good yields with high diastereomeric and enantiomeric ratios. Synthetic transformation of these products by acid hydrolysis and subsequent cyclization provide stereoselective access to bicyclic compounds containing four and five stereogenic centers with high diastereoselectivity and enantioselectivity. It is suggested that allyllithium complexes generated by asymmetric deprotonation react with most electrophiles with inversion of configuration.     

Cardiac glycosides: 3. synthesis of β-D-digitoxose analogues

Earlier studies have shown that the β-D-digitoxose (2,6-dideoxy-β-D-mannopyranose) directly attached to the cardiac glycoside steroid C3 has the greatest effect on biological activity. This report describes the synthesis of eight digitoxosides (2a-9a), with widely varying cyclic and acyclic C17β-side groups, and the corresponding C3',C4'-acetonides (2b-9b). NMR analysis of conformational strain introduced by the acetonide groups is supported by crystallographic analysis of the sugars' torsion angles.