Theoretical and experimental studies of enflurane. Infrared spectra in solution, in low-temperature argon matrix and blue shifts resulting from dimerization

Theoretical studies are performed on enflurane (CHFCl-CF(2)-O-CHF(2)) to investigate the conformational properties and vibrational spectra. Calculations are carried out at the B3LYP/6-31G(d) level along with a natural bond orbital (NBO) analysis. Experimental infrared spectra are investigated in carbon tetrachloride solution at room temperature and in argon matrix at 12 K. In agreement with previously reported data (Pfeiffer, A.; Mack, H.-G.; Oberhammer, H. J. Am. Chem. Soc. 1998, 120, 6384), it is shown that the four most stable conformers possess a trans configuration of the C-C-O-C skeleton and a gauche orientation of the CHF(2) group (with respect to the central C-O bond). These conformations are favored by electrostatic interaction between the H atom of the CHF(2) group and the F atoms of the central CF(2) group. Hyperconjugation effects from the O lone pairs to the antibonding orbitals of the neighboring C-H and C-F bonds also contribute to the stability of the four conformers. The vibrational frequencies, infrared intensities, and potential energy distributions are calculated at the same level of theory for the most stable conformers. On the basis of the theoretical results, these conformers are identified in an argon matrix. The influence of the concentration on the nu(CH) vibrations suggests the formations of higher aggregates in solution. Theoretical calculations are carried out on the enflurane dimer. The results show that the dimer is formed between two enflurane conformers having the largest stability. The dimer has an asymmetric cyclic structure, the two enflurane molecules being held together by two nonequivalent C-H...F hydrogen bonds, the C-H bond of the CHFCl group acting as a proton donor, and one of the F atoms of the CHF(2) groups acting as a proton acceptor. The theory predicts a contraction of 0.0014-0.0025 A of the two CH bonds involved in the interaction along with a blue shift of 30-38 cm(-1) of the corresponding nu(C-H) bands, in good agreement with the blue shifts of 35-39 cm(-1) observed in an argon matrix.     

One-Pot Regioselective γ-Trifluoromethylthiolation and γ-Methylthiolation of Enals

We describe herein the direct electrophilic γ-trifluoromethylthiolation and γ-methylthiolation of enals, via the in situ formation of the corresponding silyl dienol ether. This one-pot process is carried out under simple and mild reaction conditions and is compatible with a variety of functional groups.     

Diastereocontrolled addition of organometallic reagents to S-chiral N-(tert-butanesulfinyl)-α-fluoroenimines

Grignard and organolithium reagents efficiently react with (S)-N-(tert-butanesulfinyl)-α-fluoroenimines to provide chiral allylamines in excellent yields and with diastereomeric ratios of up to 96:4. Acidic removal of the sulfinyl group and simple functional group transformations allow to get enantiopure fluoroolefin dipeptide mimics.     

The norm of polynomials in large random and deterministic matrices

Let ${{\bf X}_N =(X_1^{(N)}, \ldots, X_p^{(N)})}$ be a family of N × N independent, normalized random matrices from the Gaussian Unitary Ensemble. We state sufficient conditions on matrices ${{\bf Y}_N =(Y_1^{(N)}, \ldots, Y_q^{(N)})}$ , possibly random but independent of X _N , for which the operator norm of ${P({\bf X}_N, {\bf Y}_N, {\bf Y}_N^*)}$ converges almost surely for all polynomials P. Limits are described by operator norms of objects from free probability theory. Taking advantage of the choice of the matrices Y _N and of the polynomials P, we get for a large class of matrices the ??no eigenvalues outside a neighborhood of the limiting spectrum?? phenomena. We give examples of diagonal matrices Y _N for which the convergence holds. Convergence of the operator norm is shown to hold for block matrices, even with rectangular Gaussian blocks, a situation including non-white Wishart matrices and some matrices encountered in MIMO systems.     

Combining two-directional synthesis and tandem reactions: a short formal synthesis of halichlorine

A short and efficient synthesis of an advanced intermediate (1) in the Clive route to halichlorine has been achieved in 12 steps and 13.2% yield by a combined two-directional synthesis/tandem reaction strategy.     

Intermolecular C-h amination of complex molecules: insights into the factors governing the selectivity

Transition-metal-catalyzed C-H amination via nitrene insertion allows the direct transformation of a C-H into a C-N bond. Given the ubiquity of C-H bonds in organic compounds, such a process raises the problem of regio- and chemoselectivity, a challenging goal even more difficult to tackle as the complexity of the substrate increases. Whereas excellent regiocontrol can be achieved by the use of an appropriate tether securing intramolecular addition of the nitrene, the intermolecular C-H amination remains much less predictable. This study aims at addressing this issue by capitalizing on an efficient stereoselective nitrene transfer involving the combination of a chiral aminating agent 1 with a chiral rhodium catalyst 2. Allylic C-H amination of terpenes and enol ethers occurs with excellent yields as well as with high regio-, chemo-, and diastereoselectivity as a result of the combination of steric and electronic factors. Conjugation of allylic C-H bonds with the π-bond would explain the chemoselectivity observed for cyclic substrates. Alkanes used in stoichiometric amounts are also efficiently functionalized with a net preference for tertiary equatorial C-H bonds. The selectivity, in this case, can be rationalized by steric and hyperconjugative effects. This study, therefore, provides useful information to better predict the site of C-H amination of complex molecules.     

MALDI-MS/MS with Traveling Wave Ion Mobility for the Structural Analysis of N-Linked Glycans

The preference for singly charged ion formation by MALDI makes it a better choice than electrospray ionization for profiling mixtures of N-glycans. For structural analysis, fragmentation of negative ions often yields more informative spectra than fragmentation of positive ones but such ions are more difficult to produce from neutral glycans under MALDI conditions. This work investigates conditions for the formation of both positive and negative ions by MALDI from N-linked glycans released from glycoproteins and their subsequent MS/MS and ion mobility behaviour. 2,4,6-Trihydroxyacetophenone (THAP) doped with ammonium nitrate was found to give optimal ion yields in negative ion mode. Ammonium chloride or phosphate also yielded prominent adducts but anionic carbohydrates such as sulfated N-glycans tended to ionize preferentially. Carbohydrates adducted with all three adducts (phosphate, chloride, and nitrate) produced good negative ion CID spectra but those adducted with iodide and sulfate did not yield fragment ions although they gave stronger signals. Fragmentation paralleled that seen following electrospray ionization providing superior spectra than could be obtained by PSD on MALDI-TOF instruments or with ion traps. In addition, ion mobility drift times of the adducted glycans and the ability of this technique to separate isomers also mirrored those obtained following ESI sample introduction. Ion mobility also allowed profiles to be obtained from samples whose MALDI spectra showed no evidence of such ions allowing the technique to be used in conditions where sample amounts were limiting. The method was applied to N-glycans released from the recombinant human immunodeficiency virus glycoprotein, gp120.     

Excitation symmetry analysis method (ESAM) for calculation of higher order non-linearities

A non-linear system with 3rd order non-linearity is fully characterized using symmetry analysis (SA) applied to the excitation, as it is done in 2nd order non-linear systems using the pulse inverted method. Symmetry analysis is performed using irreductible representations and the character table of C₃ rotation point group, which leads to the construction of three eigen-excitations allowing extraction of the 3rd order non-linearity parameter without the perturbation of fundamental and 2nd order terms. Validation of this concept is based on excitation symmetry analysis method (ESAM) which was tested on simulated noisy signals and compared with classical spectral analysis.