Amination of grignard reagents with retention of configuration

[see reaction]. The stereochemistry of electrophilic amination has been probed using the chiral Grignard reagent 5, in which the magnesium-bearing carbon atom is the sole stereogenic center. Amination with azidomethyl phenyl sulfide 1 and with O-sulfonyloxime 2 were found to proceed with full retention of configuration.     

Rapid conversion of hindered arylsulfonates to alkyl chlorides with retention of configuration

Arylsulfonates of hindered secondary alcohols are converted to the corresponding alkyl chlorides very rapidly and in good yields in the presence of titanium tetrachloride at low temperatures. These reactions proceed with exclusive retention of configuration.     

Stereoselective hydrolysis of sec-mono-alkyl sulfate esters with retention of configuration

An optimised method for the stereoselective hydrolysis of sec-alkylsulfate monoesters with absolute retention of configuration was developed. Under optimised conditions, clean hydrolysis of (R)-2-octyl sulfate was achieved in aqueous t-butyl methyl ether (3:97) using 0.6 equiv of p-toluenesulfonic acid as catalyst and 0.33 equiv of dioxane as mediator to give (R)-2-octanol as the sole product in the absence of side reactions, such as racemisation or elimination.     

Stereocontrolled synthesis of spiroketals via Ti(Oi-Pr)4-mediated kinetic spirocyclization of glycal epoxides with retention of configuration

A Ti(Oi-Pr)4-mediated kinetic spiroketalization reaction has been developed for the stereocontrolled target- and diversity-oriented synthesis of spiroketals. In contrast to most existing methods for spiroketal synthesis, this reaction does not rely upon thermodynamic control over the stereochemical configuration at the anomeric carbon. Stereochemically diverse glycals are first alkylated at the C1-position to introduce a hydroxyl-bearing side chain, then epoxidized stereoselectively. Treatment with Ti(Oi-Pr)4 leads to an unusual kinetic epoxide-opening spirocyclization (spirocycloisomerization) with retention of configuration at the anomeric carbon. The reaction is proposed to proceed via a chelation-controlled mechanism and has been used to form five-, six-, and seven-membered rings with stereochemically diverse substituents. This approach may also be useful for the related intermolecular beta-mannosidation reaction. This Ti(Oi-Pr)4-mediated spirocyclization is stereochemically complementary to our previously reported MeOH-induced spirocyclization, which proceeds with inversion of configuration, and together, these reactions provide comprehensive access to systematically stereochemically diversified spiroketals.     

Inversion versus retention of configuration for nucleophilic substitution at vinylic carbon

A high-level computational study using CCSD, CCSD(T), and G2(+) levels of theory has shown that unactivated vinyl substrates such as vinyl chloride would afford gas phase, single-step halide exchange by a pure in-plane sigma-approach of the nucleophile to the backside of the C--Cl sigma bond. Geometry optimization by CCSD/6-31+G* and CCSD(T)/6-31+G* confirms the earlier findings of Glukhovtsev, Pross, and Radom that the S(N)2 reaction of Cl(-) with unactivated vinyl chloride in the gas phase occurs by a sigma attack. Complexation of vinyl chloride with Na(+) does not alter this in-plane sigma preference. However, moderately activated dihaloethylenes such as 1-chloro-1-fluoroethylene undergo gas-phase S(N)2 attack by the accepted pi-route where the nucleophile approaches perpendicular to the plane of the C==C. In the latter case a single-step pi pathway is preferred for the Cl(-) + H(2)C==CFCl reaction. This is the first definitive example at a high level of theory where a single-step pi nucleophilic vinylic substitution is preferred over a multistep mechanism in the gas phase. The activation barriers for these gas-phase single-step sigma- and pi-processes involving both naked anions and Na(+) complexes are, however, prohibitively high. Solvation and the presence of a counterion must play a dominant role in nucleophilic vinylic substitution reactions that proceed so readily in the condensed phase. In solution, nucleophilic vinylic substitution reactions involving electron-withdrawing groups on the carbon--carbon double bond (e.g., -CN, -CHO, and -NO(2)) would almost certainly proceed via a free discrete carbanionic intermediate in accord with experiment.     

Nucleophilic substitution at a saturated carbon atom with retention of configuration: The reaction of trans-2-halo-3-tert-butyloxiranes with phenolates

Whereas reaction of trans-2-chloro or 2-bromo-3-tert-butyloxirane with thiophenolate occurs at C-3 to give 2-phenylmercapto-3,3-dimethylbutanal, phenolates give substitution at C-2 with retention of the oxirane ring and retention of configuration with kinetics that indicate a bimolecular mechanism.     

The direct configuration interaction method with a contracted configuration expansion

A variant of the configuration interaction method is outlined. There are four characteristic features of the method. First, the freezing, contraction of coefficients in the configuration expansion. In the present approach Rayleigh-Schrödinger perturbation theory has been used for this purpose. Second, the use of the direct CI-method to construct hamiltonian matrix elements between functions with contracted coefficients, in only one sequential read of the molecular integrals. Third, a diagonalization of the resulting small matrix. Fourth, an important computational advantage in that only one CI-vector is needed in core storage instead of two as in the usual direct CI-method. The method has been programmed for the case of all single and double replacements from a spin-unrestricted Hartree-Fock determinant. Test calculations indicate that usually less than 2% of the correlation energy is lost because of the contraction of the CI-expansion. A possibility to avoid the major part of the integral transformation and work directly with atomic basis functions is also discussed.     

Absolute configuration retention of a configurationally labile ligand during dynamic processes of thiolate protected gold clusters

Monolayer protected metal clusters are dynamic nanoscale objects. For example, the chiral Au₃₈(2-PET)₂₄ cluster (2-PET: 2-phenylethylthiolate) racemizes at moderate temperature. In addition, ligands and metal atoms can easily exchange between clusters. Such processes are important for applications of monolayer protected metal clusters; however, the mechanistic study of such processes turns out to be challenging. Here we use a configurationally labile, axially chiral ligand, biphenyl-2,2′-dithiol (R/S-BiDi), as a probe to study dynamic cluster processes. It is shown that the ligand exchange of free R/S-BiDi on a chiral Au₃₈(2-PET)₂₄ cluster is diastereospecific. Using chiral chromatography, isolated single diastereomers of the type anticlockwise/clockwise-Au₃₈(2-PET)₂₂(R/S-BiDi)₁ could be isolated. Upon heating, the cluster framework racemizes, while the R/S-BiDi ligand does not. These findings demonstrate that during cluster racemization and/or ligand exchange between clusters, the R/S-BiDi ligand is sufficiently confined, thus preventing its racemization, and exclude the possibility that the ligand desorbs from the cluster surface.

The ligand exchange between a configurationally labile BiDi ligand and intrinsically chiral Au₃₈ gold nanoclusters is diastereoselective. More importantly, the adsorbed ligand retains its configuration during dynamic cluster processes.     

Inversion vs retention of configuration in gas-phase ammonium ion/alcohol reactions

The potential energy surface for gas-phase reactions of ammonium ion with alcohols was examined by ab initio and DFT methods. Transition structures for inversion (S(N)2) and retention (S(N)F) mechanisms were located for 2-propanol and exo-2-norbornanol. The S(N)F (retention) process was found to be 6-8 kcal/mol higher in energy than the inversion S(N)2 counterpart for the 2-propanol system. The retention process in the 2-exo-norbornanol/ammonium ion system was favored by 1.3 kcal/mol.     

The Allylic Oxidation of Geraniol Catalyzed by Cytochrome P-450Cath., Proceeding with retention of configuration

Incubation of the geraniols (R)-(8-²H₁)[8-³H₁]- 1 and (S)-(8-²H₁)[8-³H₁]- 1 with microsomal cytochrome P-450_Cath. from the subtropical plant Catharanthus roseus (L.)G. DON resulted in the formation of the chiral 8-hydroxygeraniols (S)-(8-²H₁)[8-³H₁]- 2 and (R)-(8-²H₁)[8-³H₁]- 2 . Their absolute configuration was assigned on the basis of the ¹H-decoupled ³H-NMR Spectra of the corresponding dicamphanates (S)-(8-²H₁)[8-³H₁]- 9 and (R)-(8-²H₁)[8-³H₁]- 9 , of which the configurations are established in relation to the synthetic reference samples. The results clearly indicate retention of configuration during the allylic oxidation of 1 .     

Stereospecific deoxygenation of phosphine oxides with retention of configuration using triphenylphosphine or triethyl phosphite as an oxygen acceptor

[reaction: see text] A new protocol for deoxygenation of various phosphine oxides with retention of configuration is described. The advantage of the new method includes milder conditions and considerably shortened reaction times. Mechanistic studies about the oxygen transfer between the starting phosphine oxide and the sacrificial triphenylphosphine are also presented.     

Controlling diastereoselectivity in the reactions of enantiomerically pure alpha-bromoacyl-imidazolidinones with nitrogen nucleophiles: substitution reactions with retention or inversion of configuration

Diastereoselective substitution reactions of [small alpha]-bromoacyl-imidazolidinones with nitrogen nucleophiles can be promoted with either retention or inversion of configuration by carrying out reactions under epimerising or non-epimerising conditions.     

Synthesis of the enantiomers of 4-substituted γ-lactones with known absolute configuration

The highly pure enantiomers of several 4-alkyl (or alkenyl)-γ-lactones of known absolute configuration were synthesized from glutamic acid enantiomers. The key step is selective tosylate displacement rather than ring opening of the lactone tosylate (7→1) by lithium dialkylcuprate or dialkenylcuprate. The enantiomeric purity of synthesized γ-caprolactone was confirmed within the limitations of Pirkle's chiral solvating agent. The enantiomers of synthesized (Z)-6-dodecen-4-olide were used for reference to determine the enantiomeric composition of the pheromone isolated from the black-tailed deer.     

Theory of chromatography for columns with a variable configuration

Theory of ion chromatography developed in our previous work was generalized for the case of columns with variable configuration. The results obtained were used for the calculation of the efficiency of chromatography on conical columns.