Elaboration of Reactions for Organic Synthesis

EROS is based on three fundamental concepts reactors, phases, and modes. 

A reactor is defined as a container where reactions occur at the same time. These containers are a generic concept of an entity that stores the reaction. In the real world, these are equivalent to a physical container like a flask, a reaction tank, or the fragmentation space in a mass spectrometer. Each change in a reaction requires a new reactor to be instantiated. Eor instance, if starting materials are added to a container and the mixture is then heated, EROS requires two reactors one for the reactant entry and another for the heating period, where no further substances are added. Also the simulation of mass spectra using MASSIMO algorithms is performed in an individual reactor. 

The mode of a reaction defines how the starting materials of a reaction are combined to take the potential reactions into account. EROS provides several modes, which are selected mainly according to the concentration of starting materials. 

With high concentrations of starting materials, the mode MIX is selected. This mode ensures that all combinations of starting materials are considered in the generation of reactions. For instance, if three starting materials. A, B, and C are given, nine reactions will be considered three for monomolecular or pseudo-monomolecular reactions of the reactants (decomposition) three for the combinations A + B, A + C, and B + C and three for potential dimerization or polymerization of the reactants. 

In the case of lower concentrations where dimerization or polymerization is unlikely, the mode MlX NO A A is chosen. It is similar to MIX but eliminates the dimerization or polymerization reactions. 

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The EROS (Elaboration of Reactions for Organic Synthesis) system [26] is a knowledge-based system which was created for the simulation of organic reactions. Given a certain set of starting materials, EROS investigates the potential reaction pathways. It produces sequences of simultaneous and consecutive reactions and attempts to predict the products that will be obtained in those reactions. 

Synthesis design and reaction prediction can draw benefits from all these features of a computer. Our own work in this area began in 1974, and in 1978 the computer program system EROS (Elaboration of Reactions for Organic Synthesis) was first presented 6. Since then, several reports on certain aspects of the system development have appeared, but sometimes in less easily available journals or books7. Moreover, there has been no description of the overall system as it now stands. This article is intended to rectify this situation. 

The concept of a reaction may include physical and chemical changes. Some work had been done previously to model chemical reactions including the EROS (Elaboration of Reactions for Organic Synthesis) system (Gasteiger et al, 2000) and work by Sankar and Aghila (2006). PORE was developed to represent reactions as interactions between functional groups/phase systems. Each reaction would have a reaction context, which describes the pertinent descriptors of the reaction e.g. at what temperature it occurs, at... 

EROS (Elaboration of Reactions for Organic Synthesis) is a program system for the prediction of chemical reactions and the design of organic synthesis. Work on this system started more than 12 years ago. At the outset, in the overall design two fundamental decisions were taken (2) ... 

Gasteiger, J., Hutchings, M. G., Christoph, B., Gann, L., Hiller, C., Low, P., Marsili, M., Sailer, H., Yuki, K. A New Treatment of Chemical Reactivity Development of EROS (Elaboration of Reactions for Organic Synthesis), an Expert System for Reaction Prediction and Synthesis Desi . Top. Curr. Chem. 1987,137, 19-73. 

We are now presenting EROS (Elaboration of Reactions for Organic Synthesis) which has matured to the point of becoming a routine tool for the synthetic chemist. 

Parsons, P.J., Penkett, C.S., Shell, A.J. (1996) Tandem Reactions in Organic Synthesis Novel Strategies for Natural Product Elaboration and the Development of New Synthetic Methodology. Chemical Reviews, 96, 195-206. 

Recent developments have impressively enlarged the scope of Pauson-Khand reactions. Besides the elaboration of strategies for the enantioselective synthesis of cyclopentenones, it is often possible to perform PKR efficiently with a catalytic amount of a late transition metal complex. In general, different transition metal sources, e.g., Co, Rh, Ir, and Ti, can be applied in these reactions. Actual achievements demonstrate the possibility of replacing external carbon monoxide by transfer carbonylations. This procedure will surely encourage synthetic chemists to use the potential of the PKR more often in organic synthesis. However, apart from academic research, industrial applications of this methodology are still awaited. 

A large variety of organochroiniuni(III) compounds has been described. The addition reactions of these materials with carbonyl substrates represent an elaborate array of chemoselective and stereoselective processes. Because of the unique reactivity and chemical properties of these reagents, organochro-miums are useful reagents for organic synthesis. 

It is important, however, that the above-listed benefits are not gained at the expense of synthetic efficiency. Even a small decrease in yield, catalyst turnover or selectivity of a reaction can lead to a substantial increase in cost and the amount of waste generated. Fortunately, many theoretical and practical advantages of the use of water as a solvent for organic synthesis exist. These will be elaborated upon later but are briefly introduced here ... 

Photochemical reactions are not common in industry, and therefore the environmental aspect has been not considered in detail, since in most cases only small-scale explorative studies have been carried out. An important point that concerns the photochemical literature in general is that a large fraction of it is devoted to mechanistic studies. In many such studies no attempt to develop the preparative issue has been considered. This does not mean, however, that many such reactions are not suited for organic synthesis it does mean that often one has to elaborate the experimental part to make it better suited for a synthetic application rather than using the method as reported in the literature. 

Parsons PJ, Penkett CS, Shell AJ (1996) Tandem reactions in organic synthesis novel strategies for natural product elaboration and the development of new synthetic methodology. Chem Rev 96 195-206... 

A central focus in modem organic synthesis has been the development of highly efficient catalytic processes for the syntheses of natural and unnatural compounds of medicinal interest or intermediates useful for functional materials. A particularly attractive approach is to apply transition metal catalysed cyclisation reactions for the transformation of simple starting materials into monocyclic, bicyclic and polycyclic scaffolds that can be further elaborated into specific targets. 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

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