Organic synthesis reaction pathways

The reactions of carbon dioxide and carbon disulfide with organoUthium reagents have attracted much attention and have been applied in various organic synthesis. Reaction of carbon dioxide with organolithium compounds normally affords carboxylic acids after hydrolysis [50]. The formation of unsymmetrical ketones was reported from the reaction of CO2 and two organolithium compounds via an intermolecular reaction pathway [51]. When 1,4-dilithio-l,3-dienes 1 was treated with CO2, cyclopentadienone derivatives 20 with various substituents could be prepared in high yields in one-pot within several minutes via cleavage of one of the C=0 double bonds (Scheme 10) [52]. The experimental results indicate that this intermolecular reaction pattern affords cyclopentadienones in the reaction mixture before hydrolysis. 

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. 

In the fifty or so years since the discovery of a-metalated epoxides, our understanding of their reactivity has advanced to such a level that their use in routine organic synthesis is now possible. Many research groups continue to examine their unusual reaction pathways and to develop these into synthetically useful processes. In contrast, the chemistry of a-metalated aziridines is still in its infancy and there are undoubtedly many interesting facets of their nature still to be explored and applied in organic synthesis. 

Thus, photocatalysis and photogenerated catalysis indeed open up rather reach opportunities in fine organic synthesis, including some new reactions and nontraditional pathways for some known reactions. More efforts should be made in engineering of appropriate photocatalytic reactors for such synthesis. 

Olefin metathesis is one of the most important reaction in organic synthesis [44], Complexes of Ru are extremely useful for this transformation, especially so-called Grubbs catalysts. The introduction of NHCs in Ru metathesis catalysts a decade ago ( second generation Grubbs catalysts) resulted in enhanced activity and lifetime, hence overall improved catalytic performance [45, 46]. However, compared to the archetypal phosphine-based Ru metathesis catalyst 24 (Fig. 13.3), Ru-NHC complexes such as 25 display specific reactivity patterns and as a consequence, are prone to additional decomposition pathways as well as non NHC-specific pathways [47]. 

For some of the reactions described in this book, rather precise and detailed ideas about the reaction mechanism exist. However, for many catalytic reactions, the mechanistic understanding is very poor and further experimental studies are certainly needed. Calculations proved to be a highly valuable tool to gain a more precise picture of the reaction pathways. However, mostly only model systems can be studied due to the complexity of the problem. Anyway, it is the firm believe of the authors that for any reaction with an activation barrier a suitable catalyst can be found. This book shall give an insight into what has been achieved in this area concerning the synthesis of heterofunctionalized organic molecules. It is the hope of all contributors that future retro-synthetic schemes will include the catalytic approaches outlined in this book. 

Whereas in the last decade microwave irradiation was mainly applied to accelerate and optimize well-known and established reactions, current trends are indicative of the future use of microwave technology for the development of completely new reaction pathways in organic synthesis. Limited by vessel and cavity size, microwave-assisted synthesis has hitherto been focused predominantly on reaction optimiza-... 

The fourth section, on organic synthesis, discusses methods to construct complex organic syntheses using simple one-step reactions. Many groups have used the computer to search for synthetic pathways for chemical synthesis in the past. Each approach must deal with the problem of multiple possible pathways for each step in the reaction. The chapters in this section apply AI techniques to select good paths in the synthesis. 

Many of the characterization techniques described in this chapter require ambient or vacuum conditions, which may or may not be translatable to operational conditions. In situ or in opemndo characterization avoids such issues and can provide insight and information under more realistic conditions. Such approaches are becoming more common in X-ray adsorption spectroscopy (XAS) methods ofXANES and EXAFS, in NMR and in transmission electron microscopy where environmental instruments and cells are becoming common. In situ MAS NMR has been used to characterize reaction intermediates, organic deposits, surface complexes and the nature of transition state and reaction pathways. The formation of alkoxy species on zeolites upon adsorption of olefins or alcohols have been observed by C in situ and ex situ NMR [253]. Sensitivity enhancement techniques play an important role in the progress of this area. In operando infrared and RAMAN is becoming more widely used. In situ RAMAN spectroscopy has been used to online monitor synthesis of zeolites in pressurized reactors [254]. Such techniques will become commonplace. 

The structure of the carbonyl ylide reveals that it is a 1,3-dipolar species and is poised to undergo a variety of different reactions. The ability of carbonyl ylides to engage in bond-forming processes has promoted their use in organic synthesis. Although there are several pathways open to these zwitterionic intermediates, there are a few that have been the focus of detailed mechanistic and synthetic investigations (Fig. 4.2). 

In this chapter it has become clear that knowledge about the structures of organomagnesium compounds both in the solid state and in solution is often a pre-requisite for a better understanding of the reaction pathways involved in reactions of organomagnesium compounds. For the design of new synthetic pathways for the synthesis of new organic products this knowledge is of particular importance. 

For discussions of most of the reactions in this section, see Colquhoun Holton Thompson Twigg New Pathways for Organic Synthesis Plenum New York, 1984, pp. 199-204, 212-220, 234-235. For lists of reagents, with references, see Ref. 508, pp. 850-851, 855-856, 859-860. 

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