Stereochemical sensitivity

The primary motivation for the development and application of vibrational optical activity lies in the enhanced stereochemical sensitivity that it provides in relation to its two parent spectroscopies, electronic optical activity and ordinary vibrational spectroscopy. Over the past 25 years, optical rotatory dispersion and more recently electronic circular dichroism have provided useful stereochemical information regarding the structure of chiral molecules and polymers in solution however, the detail provided by these spectra has been limited by the broad and diffuse nature of the spectral bands and the difficulty of accurately modeling the spectra theoretically. 

The stereochemical sensitivity of VCD may be viewed as arising from the simultaneous interaction of linear oscillation of charge and the electric held of the IR radiation, and circular oscillation of charge and the magnetic held of the radiation. 

Some chiral drug substances either occur naturally or are synthetic derivatives of natural products. In these cases, the controls on the raw materials are often assumed to guarantee the stereochemical identity of the finished bulk drug substance product without the use of a specific stereochemically sensitive test. Such an assertion is of little significance for regulatory purposes. First, determination of the source species for an... 

The construction of a 4-pyrone is essentially the construction of a 1,3,5-tricarbonyl compound, since such compounds easily form cyclic hemiacetals then requiring only dehydration. Strong acid has usually been used for this purpose, but where stereochemically sensitive centres are close, the reagent from triphe-nylphosphine and carbon tetrachloride can be employed. ... 

In some cases, notably the spectrum of poly(propylene) [56] and poly-(vinyl alcohol) [57], the CXY chemical shifts may show resolvable stereochemical sensitivity over even longer ranges. At the next highest level, a sequence of seven monomer units or heptad, there is a total of 64 enantiomers of which 36 are distinguishable. 

Extension of CH2 stereochemical sensitivity to the next highest level entails a sequence of six monomer units, i.e. a hexad. There are 32 hexads of which 20 are distinguishable. 

Surfactants have also been of interest for their ability to support reactions in normally inhospitable environments. Reactions such as hydrolysis, aminolysis, solvolysis, and, in inorganic chemistry, of aquation of complex ions, may be retarded, accelerated, or differently sensitive to catalysts relative to the behavior in ordinary solutions (see Refs. 205 and 206 for reviews). The acid-base chemistry in micellar solutions has been investigated by Drummond and co-workers [207]. A useful model has been the pseudophase model [206-209] in which reactants are either in solution or solubilized in micelles and partition between the two as though two distinct phases were involved. In inverse micelles in nonpolar media, water is concentrated in the micellar core and reactions in the micelle may be greatly accelerated [206, 210]. The confining environment of a solubilized reactant may lead to stereochemical consequences as in photodimerization reactions in micelles [211] or vesicles [212] or in the generation of radical pairs [213]. 

T[[dotb]he nature of the initial attack by the water (eq. 10) is a matter of some controversy (205,206). Stereochemical and kinetic studies of model systems have been reported that support trans addition of external water (207,208) or internal addition of cis-coordinated water (209), depending on the particular model system under study. Other paHadium-cataly2ed oxidations of olefins ia various oxygen donor solvents produce a variety of products including aldehydes (qv), ketones (qv), vinyl acetate, acetals, and vinyl ethers (204). However the product mixtures are complex and very sensitive to conditions. 

Conjugated dienes can undergo a variety of photoreactions, depending on whether excitation is direct or photosensitized. The benzophenone-sensitized excitation of 1,3-pentadiene, for example, results in stereochemical isomerization and dimerization ... 

The reaction products are the same for both direct irradiation and acetophenone sensitization. When the reactant B is used in homochiral form, the product D is nearly racemic (6% e.e.). Relate the formation of the cyclobutanones to the more normal products of type E and E Why does the 5-aryl substituent favor formation of the cyclobutanones Give a complete mechanism for formation of D which is consistent with the stereochemical result. 

In general, (Z)-[2-(4-methylphenylsulfmyl)ethenyl]benzenes undergo addition with higher diastereoselectivity than their. -counterparts. The stereochemical outcome for ( )-[2-(4-methyl-phenylsulfinyl)ethcnyl]benzene is more sensitive to the metal counterion and reaction solvent1,2. For ( )-[2-(4-methylphenylsulfmyl)ethenyl]benzene a reverse in product diastereoselection is observed when the metal counterion/solvent is changed from Na/ethanol to Li/THF1. 

We expect the E2 pathway to predominate, because it is less sensitive to steric hindrance than the Sn2 pathway. Therefore, we would expect the major product(s) to be generated via an E2 process, and the minor product(s) to be generated via an Sn2 process. In order to draw the products, we must complete the third and final step. That is, we must consider the regiochemical and stereochemical outcomes for both the E2 and Sn2 processes. Let s begin with the E2 process. 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

The focus of Part B is on the closely interrelated topics of reactions and synthesis. In each of the first twelve chapters, we consider a group of related reactions that have been chosen for discussion primarily on the basis of their usefulness in synthesis. For each reaction we present an outline of the mechanism, its regio- and stereochemical characteristics, and information on typical reaction conditions. For the more commonly used reactions, the schemes contain several examples, which may include examples of the reaction in relatively simple molecules and in more complex structures. The goal of these chapters is to develop a fundamental base of knowledge about organic reactions in the context of synthesis. We want to be able to answer questions such as What transformation does a reaction achieve What is the mechanism of the reaction What reagents and reaction conditions are typically used What substances can catalyze the reaction How sensitive is the reaction to other functional groups and the steric environment What factors control the stereoselectivity of the reaction Under what conditions is the reaction enantioselective ... 

Bioassay of alternate molecular forms supports the view that the ORs are capable of resolving isomeric distinctions in neutral (non-biological) odourants. Stereochemical pairs of odours were tested for differential sensitivities in the blind subterranean mole rat (Spalax ehrenbergi). The subjects responded to one enantiomer, but not to its stereoisomer. Both sexes were attracted to the odour of R-(-)-carvone but unresponsive to S-(+)-carvone in contrast, males and females were repelled by the odour of (+)-citronellol, but not by (-)-citronellol (Heth et al., 1992). The lack of responsiveness by mole rats could be central due to lack of salience, or peripheral due to hyposmia/anosmia for one isomer. Both carvones have distinct odours for the human nose. 

In order to defer stereochemical questions we will consider first the photoreaction of 6,6-diphenyl-cyclohexa-2,5-dienone (6). Either direct or sensitized photolysis<3,7,8) of compound (6) in aqueous dioxane follows the following course ... 

Similar studies have been conducted on poly(vinyl chloride) (PVC) to assign different IR signatures obtained from different stereo-configurational isomers. The sensitivity of the vC-Cl bond on the stereochemical environment has been utilized using IR spectroscopy. The characteristic vibrations of the vC-Cl bonds are inherently tied in to the configuration as well as the conformation of the... 

WIN 64821 (10) and (—)-ditryptophenaline (11) syntheses [7], not only effectively differentiated the two amide moieties but also most importantly marked the first in a series of stereochemical transfer steps in which the stereochemistry of the constituent L-amino acids was relayed to ultimately define each of the relative and absolute stereochemical configurations at all eight stereogenic centers found in the target compound. Finally, /V-methylation of the base-sensitive amide in 77 % yield using methyl iodide and potassium carbonate in acetone completed the 5-step synthesis of our key tetracyclic bromide monomer starting from commercially available amino acid derivatives. 

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