Organic transformations Diels-Alder reactions

In Chapter 2 the Diels-Alder reaction between substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-ones (3.8a-g) and cyclopentadiene (3.9) was described. It was demonstrated that Lewis-acid catalysis of this reaction can lead to impressive accelerations, particularly in aqueous media. In this chapter the effects of ligands attached to the catalyst are described. Ligand effects on the kinetics of the Diels-Alder reaction can be separated into influences on the equilibrium constant for binding of the dienoplule to the catalyst (K ) as well as influences on the rate constant for reaction of the complex with cyclopentadiene (kc-ad (Scheme 3.5). Also the influence of ligands on the endo-exo selectivity are examined. Finally, and perhaps most interestingly, studies aimed at enantioselective catalysis are presented, resulting in the first example of enantioselective Lewis-acid catalysis of an organic transformation in water. 

Of all the work described in this thesis, this discovery is probably the most significant. Given the fact that the arene - arene interactions underlying the observed enantioselectivity of ftie Diels-Alder reactions described in Chapter 3 are also encountered in other organic reactions, we infer that, in the near future, the beneficial influence of water on enantioselectivity can also be extended to these transformations. Moreover, the fact that water can now be used as a solvent for enantioselective Lewis-add catalysed reactions facilitates mechanistic studies of these processes, because the number of equilibria that need to be considered is reduced Furthermore, knowledge and techniques from aqueous coordination chemistry can now be used directly in enantioselective catalysis. 

Many organic chemical transformations have been carried out in ionic liquids hydrogenation [4, 5], oxidation [6], epoxidation [7], and hydroformylation [8] reactions, for example. In addition to these processes, numerous synthetic routes involve a carbon-carbon (C-C) bond-forming step. As a result, many C-C bondforming procedures have been studied in ambient-temperature ionic liquids. Among those reported are the Friedel-Crafts acylation [9] and allcylation [10] reactions, allylation reactions [11, 12], the Diels-Alder reaction [13], the Heck reaction [14], and the Suzuld [15] and Trost-Tsuji coupling [16] reactions. 

Biocatalysts have received great attention in these last few years. Due to their capacity to perform asymmetric transformations under mild conditions [78], they have been useful tools for synthesizing optically active organic molecules. They promote a variety of chemical transformations, including the syntheses of esters and amides and oxidations, reductions, eliminations and carbon carbon forming. Little is known about biocatalyst-promoted Diels Alder reactions. 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

In 1960, Yates and Eaton (192) demonstrated that Lewis acids can dramatically accelerate the Diels-Alder reaction. In principle, any transformation wherein coordination of a Lewis acid may reduce the gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of a given set of reactants should be susceptible to Lewis acid catalysis. Indeed, numerous important carbon-carbon bond-forming organic transformations have been shown to be amenable to rate acceleration by a Lewis acid. In many cases, the use... 

At first glance the Diels-Alder reaction represents an organic transformation which is relatively insensitive to solvent effects (Table 9). For the dimerization of cyclopentadiene, the second-order rate constants in a broad range of organic solvents are quite similar5. The data of Table 9 refer to the special case of a Diels-Alder reaction between two pure hydrocarbons. Usually, Diels-Alder reactions only proceed at an appreciable rate when either the diene or the dienophile is activated by electron-donating or electron-withdrawing... 

The present chapter aims at introducing the reader to the emerging field of organic synthesis in water as exemplified by the well-known Diels-Alder reaction. As this transformation is exceptionally well understood mechanistically and highly valuable for building complex structures, it lends itself to examining and probing the effects of aqueous media and other factors which influence the reactivities and selectivities. 

In summary, we hope to have demonstrated that aqueous media for organic reactions, specifically the Diels-Alder reaction, are neither a curiosity only applicable to unusual transformations nor are they a limitation for catalysis. It is more than likely that the potential of water as an environmentally friendly and safe solvent will be used more effectively in the future for a large number of different reactions. 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

The Diels-Alder reaction is a valuable transformation for the construction of complex carbocycles, and represents arguably one of the most powerful approaches in organic chemistry. In particular, catalytic enantioselective variants have received unprecedented attention [22], representing an appealing starting point for the development of MacMillan s concept of iminium catalysis. 

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