Stereochemical Terms Research Articles

Stereochemical aspects of cyclotriphosphazenes: Prochiral and pseudo-asymmetric phosphorus atoms

Mono-, di- and trispiro derivatives (2–6) from the reaction of hexachlorocyclotriphosphazene, (1) with 3-aminobenzyl alcohol were reported in order to illustrate stereochemical terms such as prochiral, pseudo-asymmetry, homo-, enantio- and diastereotopic atoms or groups. The dispiro derivatives (3 and 4) were shown to exist as trans and cis geometric isomers and be racemic (RR/SS) and meso (RS), respectively, whereas the trispiro derivatives (5 and 6) exist as cis and trans geometric isomers and are achiral. Pseudo-asymmetry was introduced into the meso form (4) containing two constitutionally equivalent chiral units by the reactions with either 3-amino-1-propanol or phenol. The two meso diastereoisomeric forms, which can be assigned as R,s,S (7a) and R,r,S (7b) or S,s,R (8a) and S,r,R (8b), were identified as the systematic examples of cyclophosphazene derivatives including pseudo-asymmetric phosphorus centers. The corresponding racemic form (3) produced only one diastereoisomer (9 and 10) for each reaction. All the compounds were analysed by standard spectroscopic techniques, such as elemental analysis, MALDI-TOF mass spectrometry, NMR spectroscopy and X-ray crystallography (for 2, 4 and 6). The stereogenic properties of the compounds were confirmed by 31P NMR spectroscopy on addition of the chiral solvating agent (CSA) (R)-(+)-2,2,2-trifluoro-1-(90-anthryl)ethanol.

Corrigendum: Hydroxy-Directed Ruthenium-Catalyzed Alkene/Alkyne Coupling: Increased Scope, Stereochemical Implications, and Mechanistic Rationale.

The recognition of the dual binding mode of propargyl and allyl alcohols to [Cp*Ru] fragments fostered the development of a highly regioselective intermolecular Alder-ene-type reaction of alkynes with 1,2-disubstituted alkenes. The increased substrate scope opens new perspectives in stereochemical terms. As the loaded catalyst is chiral-at-metal, stereochemical information is efficiently relayed from the propargylic site to the emerging C-C bond. This interpretation is based on the X-ray structure of the first Cp*Ru complex carrying an intact enyne ligand, and provides valuable insights into bonding and activation of the substrates. Computational data draw a clear picture of the principles governing regio- and stereocontrol.

Hydroxy-Directed Ruthenium-Catalyzed Alkene/Alkyne Coupling: Increased Scope, Stereochemical Implications, and Mechanistic Rationale.

The recognition of the dual binding mode of propargyl and allyl alcohols to [Cp*Ru] fragments fostered the development of a highly regioselective intermolecular Alder-ene-type reaction of alkynes with 1,2-disubstituted alkenes. The increased substrate scope opens new perspectives in stereochemical terms. As the loaded catalyst is chiral-at-metal, stereochemical information is efficiently relayed from the propargylic site to the emerging C-C bond. This interpretation is based on the X-ray structure of the first Cp*Ru complex carrying an intact enyne ligand, and provides valuable insights into bonding and activation of the substrates. Computational data draw a clear picture of the principles governing regio- and stereocontrol.

Hydroxy‐Directed Ruthenium‐Catalyzed Alkene/Alkyne Coupling: Increased Scope, Stereochemical Implications, and Mechanistic Rationale

AbstractThe recognition of the dual binding mode of propargyl and allyl alcohols to [Cp*Ru] fragments fostered the development of a highly regioselective intermolecular Alder‐ene‐type reaction of alkynes with 1,2‐disubstituted alkenes. The increased substrate scope opens new perspectives in stereochemical terms. As the loaded catalyst is chiral‐at‐metal, stereochemical information is efficiently relayed from the propargylic site to the emerging C−C bond. This interpretation is based on the X‐ray structure of the first Cp*Ru complex carrying an intact enyne ligand, and provides valuable insights into bonding and activation of the substrates. Computational data draw a clear picture of the principles governing regio‐ and stereocontrol.

The Same and Not the Same: Chirality, Topicity, and Memory of Chirality

A simple molecular approach is described that aids students in learning challenging stereochemical terms, definitions, and concepts, particularly when chemical structures are drawn in two dimensions. The approach starts with a structurally diverse family of natural compounds (a-amino acids) and gradually increases in complexity. The recently coined term memory of chirality, which has become commonly used in the last decade, is introduced in this approach. Photochemical reactivity is used as the tool to understand stereochemical terms.

Stereochemical terminology and its discontents.

Scrutiny of the purported misuse of some current stereochemical terms shows that obsolescence and faulty syntax may be less of a problem than previously assumed. Furthermore, changes in stereochemical terminology over time are not always due to obsolescence or to novel developments in chemical technology; for example, technical developments played no role whatsoever in the semantic transmutations over time of the terms "diastereomer" and "pseudoasymmetry." Finally, definitions of many stereochemical terms acquire meaning only within a given context and therefore cannot always be easily formulated. A prime example is the definition of "chirality," the concept at the heart of stereochemistry and, not coincidentally, the name of the journal in which this essay appears in print.

Ring Closing Alkyne Metathesis. Comparative Investigation of Two Different Catalyst Systems and Application to the Stereoselective Synthesis of Olfactory Lactones, Azamacrolides, and the Macrocyclic Perimeter of the Marine Alkaloid Nakadomarin A

Previously unknown ring closing metathesis reactions of diynes are described which open an efficient and stereoselective entry into macrocyclic (Z)-alkenes if the resulting cycloalkyne products are subjected to Lindlar reduction. This new two-step strategy offers significant advantages in stereochemical terms over conventional RCM of dienes which usually leads to (E,Z)-mixtures when applied to the formation of large rings. The tungsten alkylidyne complex (tBuO)3W⋮CCMe3(1a) and analogues thereof as well as a structurally unknown species formed in situ from Mo(CO)6 and p-chlorophenol effect the crucial alkyne metathesis reactions in a highly efficient manner, with the former catalyst being more tolerant toward structural variations of the substrates and polar functional groups. Applications to the stereoselective synthesis of the olfactory compounds ambrettolide 23 and yuzu lactone 24, the insect repellent azamacrolides epilachnene 31 and homoepilachnene 33, as well as to the fully functional building block...

Principles of asymmetric synthesis

Introduction. Why we do asymmetric synthesis. What is an asymmetric synthesis? Stereoselectivity: intraligand vs. interligand asymmetric induction. Selectivity: kinetic and thermodynamic control. Single and double asymmetric induction. Glossary of stereochemical terms. References. Analytical Methods. The importance of analysis, and which method to choose. Polarimetry, the old fashioned way. Nuclear magnetic resonance. Chromatography. Summary. References. Enolate, Azaenolate, and Organolithium Alkylations. Enolates and azaenolates. Chiral organolithiums. References. 1,2 and 1,4 Additions to Carbonyls. Cram's rule: open-chain model. Cram's rule: rigid, chelate, or cyclic model. Additions using chiral catalysts or chiral nucleophiles. Conjugate additions. References. Aldol and Michael Additions of Allyls and Enolates. 1,2-Additions of allyl metals and metalloids. Aldol additions. Michael additions. References. Rearrangements and Cycloadditions. Rearrangements. Cycloadditions. References. Reductions and Hydroborations. Reduction of carbon-heteroatom double bonds. Reduction of carbon-carbon bonds. Hydroborations. References. Oxidations. Introduction and scope. Epoxidation and related reactions. Dihydroxylations. Oxidation of enolates and enol ethers. Miscellaneous oxidations. References. Index.

Infelicitous stereochemical nomenclature

Misuse of current stereochemical terms is discussed, including terms that should be avoided altogether and replaced by other, standard ones. The reasons for using the proper terms and avoiding the infelicitous ones are pointed out. Chirality 9:428–430, 1997. © 1997 Wiley-Liss, Inc.

Infelicitous stereochemical nomenclature

Misuse of current stereochemical terms is discussed, including terms that should be avoided altogether and replaced by other, standard ones. The reasons for using the proper terms and avoiding the infelicitous ones are pointed out. Chirality 9:428–430, 1997. © 1997 Wiley-Liss, Inc.

Synthesis and biological activity of the diphosphorylphosphonate derivatives of (+)- and (–)-cis-9-(4′-hydroxycyclopent-2′-enyl)guanine

The carbovir triphosphate analogue 10 and its enantiomer 11 have been synthesized and tested as inhibitors of HIV-reverse transcriptase; the enantiomer 11, more remotely resembling natural nucleotides in stereochemical terms, is surprisingly the more active compound.

Toward the consistent use of regiochemical and stereochemical terms in introductory organic chemistry

Proposes consistency and clarity in the use of definitions for regioselective, stereoselective, and stereospecific in introductory organic chemistry.

Concluding remarks

This is the second time that I have been asked to make the concluding remarks at a Royal Society Discussion Meeting on enzyme mechanisms. The first occasion was in 1966, shortly after D. C. Phillips and his colleagues had solved the structure of the first enzyme, lysozyme, in the Davy Faraday Laboratory at the Royal Institution. It was also the first time that anyone had been able to interpret the catalytic mechanism of an enzyme in stereochemical terms.

ChemInform Abstract: X‐RAY STRUCTURE, ABSOLUTE CONFIGURATION, AND CIRCULAR DICHROISM SPECTRA OF COBALT AND CHROMIUM MALONATE COMPLEXES AS THEIR DIASTEREOISOMERS, Δ(CO((‐)1,2‐DIAMINOPROPANE)3)Λ(M(MALONATE)3),3H2O

The complexes K3[M(malonate)3](M = Co or Cr) have been resolved via their diastereoisomers with (–)589[Co{(–)1,2-(diaminopropane)}3]Br3. The only diastereoisomers precipitated are shown to have the absolute configurations Δ[Co{(–)1,2-diaminopropane}3]Λ[M(malonate)3],3H2O where M is (+)589Cr or (–)589Co. Crystals of the chromium diastereoisomer are rhombohedral, space group R32, with hexagonal lattice parameters, a= 16.12(2), c= 10.07(2)A, and Z= 3. The structure was solved by Patterson and Fourier methods, and refined by full-matrix least-squares calculations to R 0.073 for 435 independent reflexions collected photographically. Both complex ions are disordered on sites of symmetry 32, and are linked in columns by three N–H ⋯ O hydrogen bonds. The columns of complexes are connected by hydrogen bonds involving both anion and cation. The cation adopts the expected Δ(λλλ) conformation with the methyl groups equatorial on the gauche rings. The malonate chelate ring skeleton is planar except for the methylene carbon atom. The absolute configuration of the (+)589[Cr(malonate)]33– ion is opposite to an earlier assignment based on spectroscopic data. The circular dichroism spectra of the diastereoisomers as KBr discs show one less peak than is observed in the solution spectra of both Δ[M(malonate)3]3+ complexes in the region of their T1g transitions. The remaining peak has the same sign for both cobalt and chromium complexes. In these spectra and in those of the diastereoisomers Λ[M(oxalate)3]Λ[Co(ethylenediamine)3](M = Co or Cr), the region of the T1g transition of the tris(diamine) cations resemble the c.d. spectra of these cations in solution with added phosphate ion. The structure of the tris(malonate) diastereoisomer shows a similar hydrogen bonding scheme to that of a phosphate salt of the cation. In these diastereoisomers the complex cations have a similar effect in influencing the transition moments of the oxalato- and malonato-complex anions and it is therefore not readily possible to interpret solid to solution spectral changes in stereochemical terms.

X-Ray structure, absolute configuration, and circular dichroism spectra of cobalt and chromium malonate complexes as their diastereoisomers, Δ[Co{(–)1,2-diaminopropane}3]Λ[M(malonate)3],3H2O

The complexes K3[M(malonate)3](M = Co or Cr) have been resolved via their diastereoisomers with (–)589[Co{(–)1,2-(diaminopropane)}3]Br3. The only diastereoisomers precipitated are shown to have the absolute configurations Δ[Co{(–)1,2-diaminopropane}3]Λ[M(malonate)3],3H2O where M is (+)589Cr or (–)589Co. Crystals of the chromium diastereoisomer are rhombohedral, space group R32, with hexagonal lattice parameters, a= 16.12(2), c= 10.07(2)Å, and Z= 3. The structure was solved by Patterson and Fourier methods, and refined by full-matrix least-squares calculations to R 0.073 for 435 independent reflexions collected photographically. Both complex ions are disordered on sites of symmetry 32, and are linked in columns by three N–H ⋯ O hydrogen bonds. The columns of complexes are connected by hydrogen bonds involving both anion and cation. The cation adopts the expected Δ(λλλ) conformation with the methyl groups equatorial on the gauche rings. The malonate chelate ring skeleton is planar except for the methylene carbon atom. The absolute configuration of the (+)589[Cr(malonate)]33– ion is opposite to an earlier assignment based on spectroscopic data. The circular dichroism spectra of the diastereoisomers as KBr discs show one less peak than is observed in the solution spectra of both Δ[M(malonate)3]3+ complexes in the region of their T1g transitions. The remaining peak has the same sign for both cobalt and chromium complexes. In these spectra and in those of the diastereoisomers Λ[M(oxalate)3]Λ[Co(ethylenediamine)3](M = Co or Cr), the region of the T1g transition of the tris(diamine) cations resemble the c.d. spectra of these cations in solution with added phosphate ion. The structure of the tris(malonate) diastereoisomer shows a similar hydrogen bonding scheme to that of a phosphate salt of the cation. In these diastereoisomers the complex cations have a similar effect in influencing the transition moments of the oxalato- and malonato-complex anions and it is therefore not readily possible to interpret solid to solution spectral changes in stereochemical terms.

Mass spectral study of cyclic alkaneboronates of sugar phosphates. Evidence of interaction between the phosphate group and boron under electron‐impact conditions

AbstractCyclic butane‐ and methaneboronic esters of dimethylphosphates of glucose, galactose, mannose, fructose and methyl gluconate have been examined by mass spectrometry. High resolution information and deuterium labeling of all six carbons of glucose, as well as of the methylphosphate groups, permits elucidation of the origin of various ions, which can be grouped according to their probable mechanism of formation. In each case, the intensity of the [M – R]+ ion can be rationalized, in stereochemical terms, by the ease with which incipient positive charge on boron can be stabilized by the phosphate group. This interaction also gives rise to rearrangement ions containing a BOP linkage. Other effects of structure on fragmentation pattern are discussed. Retention of specific portions of the glucose skeleton in ions with clearly defined label shift behavior, as well as the preservation of intact sugar moieties in intense [M – R]+ ions, suggests applications for stable isotope analyses. These are discussed in terms of their advantages over silicon‐containing derivatives.

Carrageenans. Part IV. Variations in the structure and gel properties of κ-carrageenan, and the characterisation of sulphate esters by infrared spectroscopy

Structures of the ‘masked repeating’ type seem to occur generally in κ-carrageenans from Chondrus crispus and Gigartina species and will account for the analytical variation between one sample and another. Most—possibly all—of the variation is in the 4-linked units which occur as 3,6-anhydrogalactose, 3,6-anhydrogalactose 2-sulphate, galactose 6-sulphate, and galactose 2,6-disulphate. In κ-carrageenan from G. stellata, as from C. crispus, all galactose units are believed to have the D-configuration. Samples from Chondrus were similar to each other and had a lower content of both types of 2-sulphate than those from Gigartina. The separation of a Chondrus sample into a series of subfractions which differed in the relative proportions of the various 4-linked units, suggests that κ-carrageenan might normally contain a mixture of related molecules. Evidence is given that absorption bands shown by sulphated 3,6-anhydrogalactose units in the 800–850 cm.–1 region of the infrared spectrum cannot be interpreted in the simple stereochemical terms used previously. However, many carrageenans show a band at about 805 cm.–1 which is characteristic of 3,6-anhydrogalactose sulphate and potentially useful because it is easily recognised, even in the presence of other sulphate esters. Gel formation by κ-carrageenan is enhanced by removal of 6-sulphate with conversion into 3,6-anhydrogalactose, but is much less sensitive to an excess of 2-sulphate. The variation of gel strength with polysaccharide structure provides some evidence on the molecular basis of gel formation.

Concluding remarks

For the first time we have been able to interpret the catalytic activity of an enzyme in stereochemical terms. It seems rash to generalize from the structure of one enzyme, but we may broaden our base by elevating myoglobin and haemoglobin to the rank of honorary enzymes, as Monod has suggested, and call the haem groups their active sites. What these three proteins have in common is the distribution of polar and nonpolar side chains; the interior of the lysozyme as well as that of the globin chains is made up largely of hydrocarbons, providing a medium of low dielectric constant. In each case the active centre lies in a pocket formed by this non-polar medium, and the pocket contains some polar residues which are essential for activity.