Integrated Discussion on Stereogenicity and Chirality for Restructuring Stereochemistry

To discuss the difference between stereogenicity and chirality, we propose the concept of RS-stereoisomeric groups. Beginning with this concept, we have further proposed the concepts of holantimers, stereoisograms, and RS-stereogenicity. Thereby, we have clarified that the concept of RS-stereogenicity, but not conventional stereogenicity, is closely related to chirality. Thus, five RS-stereogenicity types are defined and examined to discuss the difference between stereogenicity and chirality. Combinatorial enumerations have also been studied by considering the RS-stereogenicity.     

Conceptual defects of modern stereochemistry. Comprehensive remedy by stereoisograms based on RS-stereoisomerism for mediating between enantiomerism and stereoisomerism

The recognition of chirality as a single kind of handedness is a conceptual defect of modern stereochemistry, which has caused serious confusion in its theoretical foundations and stereochemical nomenclature. To remedy this defect, RS-stereogenicity is developed as another kind of handedness. These two kinds of handedness are integrated to give RS-stereoisomerism, which is formulated diagrammatically by stereoisograms. During the process of the remedy, the lack of the concept of ligand reflections has been revealed as another conceptual defect. The lack of the concept of orbits (equivalence classes) has been found to be one more defect, which has caused a misleading classification of isomers. By adopting the concept of orbits, the revised hierarchy of isomerism is developed, i.e., isomers $?$ isoskeletomers $?$ stereoisomers $?$ RS-stereoisomers $?$ enantiomers $?$ 3D-structures. Thereby, the theoretical foundations of modern stereochemistry are restructured rationally.     

Pseudoasymmetry, stereogenicity, and the RS-nomenclature comprehended by the concepts of holantimers and stereoisograms

The concepts of holantimer and stereoisogram are applied to comprehensive discussions on the term ‘pseudoasymmetry’, where the concept of RS-stereogenicity is used as a more definite concept than usual stereogenicity. Thereby, three relationships contained in each stereoisogram can be definitely specified: an enantiomeric relationship is related to chiral/achiral, an RS-diastereomeric relationship is related to RS-stereogenic/RS-astereogenic, and a holantimeric relationship is related to scleral/ascleral, which is coined to keep the terminology in a balanced fashion. Such stereoisograms are classified into five types (Types I-V) by virtue of the three relationships. Among them, Type I, III, and V are selected as a set of RS-stereogenic units: chiral/ascleral RS-stereogenic unit (or Type I unit), chiral/scleral RS-stereogenic unit (or Type III unit), and achiral/scleral RS-stereogenic unit (or Type V unit). Thereby, the term ‘pseudoasymmetric stereogenic units’ should be replaced by the term ‘achiral/scleral RS-stereogenic units’ (or ‘Type V units’).     

Pseudoasymmetrie in der organischen Chemie

The geometrical foundations of ‘pseudoasymmetry’ and several other related concepts of organic stereochemistry such as ‘prochirality’ and ‘propseudoasymmetry’ in two- and three-dimensional space have been explored. As a consequence some modifications of the R,S system for specification of molecular chirality and stereoisomerism are proposed.     

Isoskeletomerism as an intermediate concept for mediating between stereoisomerism and isomerism. A remedy for conceptual defects of organic chemistry

After isoskeletomerism is introduced as an intermediate concept for mediating between stereoisomerism and isomerism, so-called ‘constitutional isomerism’ is critically discussed as one of the roots of confusion in organic chemistry. The convention that isomerism is subdivided into stereoisomerism and ‘constitutional isomerism’ is concluded to be misleading, because these concepts are conceptually distinct from a viewpoint of the concepts of equivalence relationships and equivalence classes. The indifference toward these concepts is one of the conceptual defects of organic chemistry. A new flowchart for judging enantiomerism, RS-stereoisomerism, stereoisomerism, isoskeletomerism, and isomerism is discussed to generate an isomer-classification diagram, where RS-stereoisomerism and isoskeletomerism are contained as new matters for remedying the conceptual defects. Skeletons are derived from basic skeletons by three operations (the bond operation, the replacement operation, and the substitutive operation), and they are used to examine the action of isoskeletomeric relationships. Equivalent molecular entities under an isoskeletomeric relationship are collected to give a set of isoskeletomers, which is concluded to be an equivalence class. The confusion caused by so-called ‘constitutional isomerism’ and its subcategories (‘skeletal isomerism’, ‘positional isomerism’, and so on) is critically discussed from the viewpoint of isoskeletomerism as a missing link. The double-entendre of the term constitution is examined when applied to both a 3D entity (a set of stereoisomers) and a 2D entity (a graph). Taxonomy of organic compounds and rational formulas, nomenclature of organic compounds, and combinatorial enumeration of chemical compounds are discussed from the viewpoint of isoskeletomerism.     

Stereochemical analysis of α1, a mating hormone of the phytopathogen Phytophthora

The stereochemistry of α1, the first identified mating hormone of the plant pathogen Phytophthora, has been unknown due to its acyclic flexible nature. Here, two stereogenic centers of α1 are determined to be (3RS,15R)-configuration by NMR analysis of the Mosher’s esters of α1 and a synthetic model compound. The information obtained here will be helpful for reducing the burden of the researchers who are trying to synthesize all the possible stereoisomers of α1 to elucidate its full stereochemistry.     

Control of Diels-Alder Addition,Stereo- and Regioselectivity by Remote Substituents and Tricarbonyl(diene)iron Moieties

A stereoselective synthesis of tricarbonyl-[((1RS,2RS,4RS,5RS,6RS)-C-5,6,C-η-(5,6,7,8,-tetramethylidenbicyclo[2.2.2]octan-2-ol)]iron ( 11 ),and of its tosylate 12 and benzoate 13 is reported. The bulk of the ‘endo’-Fe(CO))³ moiety and of the ester groups in 13 renders its Diels-Alder additions to methyl propynoate ( 15 )), butynone ( 16 ), and 1-cyanovinyl acetate highly ‘para’ regioselective. The cycloadditions of diene-alcohol 11 are either ‘meta’- or ‘para’-regioselective depending on the nature of the dienophile. In the presence of BF ₃. Et ₂O, the addition of 11 to methyl vinyl ketone is highly stereo- (Alder mode) and ‘para’-regioselective, giving adduct 52 (tricarbonyl [((1 RS,4RS,8RS,9RS,10RS,12RS)-C,9,10,C-η-(12-hydroxy-9,10-dimethylidenetricyclo[6.2.2.0^2,7]dodec-2(7)-en-4 yl methyl ketone)]iron) whose structure has been established by single-crystal X-ray crystallography.