Diels neutral electron demand

Diels-Alder Reactions with Neutral Electron Demand... 

Diels-Alder reactions can be divided into normal electron demand and inverse electron demand additions. This distinction is based on the way the rate of the reaction responds to the introduction of electron withdrawing and electron donating substituents. Normal electron demand Diels-Alder reactions are promoted by electron donating substituents on the diene and electron withdrawii substituents on the dienophile. In contrast, inverse electron demand reactions are accelerated by electron withdrawing substituents on the diene and electron donating ones on the dienophile. There also exists an intermediate class, the neutral Diels-Alder reaction, that is accelerated by both electron withdrawing and donating substituents. 

The generation of six-membered ring systems by means of cycloaddition reactions can be divided into two main approaches. The first is the cyclotrimerizationofalkynes utilizing low-valent iron catalyst systems, whereas the second approach is the Diels-Alder (DA) reaction of a diene and a dienophile. The latter reaction can itself be divided into three subclasses DA reactions with normal, neutral and inverse electron demand are known. The electronic structure of the educts dictates the oxidation state of the catalyst system required to perform the diverse classes of DA reactions. Nevertheless, for each subclass examples can be found. 

The decrease of electron density necessary for inverse electron demand aza Diels-Alder reactions can also be effected by appropiate substituents attached to C-2, especially by a cyano moiety. Several l-aza-2-cyano-1,3-butadienes have been investigated by Fowler and his coworkers in this context [243-245]. Strikingly, the easily accessable 1-aza-l,3-butadiene 3-29 undergoes cycloaddition not only with electron-rich dienophiles, it reacts as well with neutral and even with electron-deficient dienophiles (Fig. 3-10) [246,247],... 

Narsaiah and Krishnaiah (2002) reported that the hetero-Diels-Alder reaction of A(-acetyl perflnoroalkyl substituted 2(1//) pyridones with DMAD on neutral alumina under solvent-free microwave irradiation conditions extended to undergo an inverse electron demand hetero-Diels-Alder reaction, resulting exclusively in E, Z isomers (3 1) of Michael-type A-adducts. 

The Diels-Alder reaction may be subclassified into three types of [4 + 2] cycloaddition reactions (1) the normal Diels-Alder reaction appropriately referred to as a HOMOdiene-controlled [4 + 2] cycloaddition reaction (2) the neutral Diels-Alder reaction and (3) the inverse electron demand or LUMOdiene-controlled Diels-Alder reaction (Figure 1). Historically, it has been the normal or HOMOdiene-controlled Diels-Alder reaction comprised of the [4 + 2] cycloaddition reaction of an electron-rich diene and an electron-deficient dienophile that has serviced the preparative needs of organic chemistry and has occupied the central focus of mechanistic and theoretical studies. Pertinent to the topic of this chapter and the inherent electron-deficient nature of all fundamental heterodienes (Table 1), the LUMOdiene-controlled Diels-Alder reaction possesses a characteristic rate acceleration and high levels of predictable regio- and diastereo-control comparable with those observed in the HOMOdiene-controlled Diels-Alder reaction. 

The thermal [4+2] Diels-Alder cycloaddition reaction can be classified into three processes the normal Diels-Alder reaction of electron-rich dienes with electron-deficient dienophiles (HOMOdiene-controlled), the neutral Diels-Alder reaction and the inverse electron-demand Diels-Alder reaction of electron-deficient dienes with electron-rich dienophiles (LUMOdiene-controlled). 

Several examples exist of inverse electron demand Diels-Alder reactions involving electron-deficient sym-tetrazines acting as dienes. However, the neutral, electon-rich imino compounds involved in these cycloadditions do not generally e pear to be useful dienophiles with other types of dienes. 

An extensively investigated and useful hetero-2-azadiene system capable of 4it participation in Diels-Alder reactions is the vinylnitroso compounds.75-78 The complementary addition of electron-withdrawing substituents to the 3 position of the vinylnitroso system enhances the rate of diene participation in inverse electron demand Diels-Alder reactions with electron-rich or neutral dienophiles (simple olefins).75,76 Table 9-IV summarizes a series of representative examples of the 47r participation of vinylnitroso compounds in Diels-Alder reactions, and an extensive review has summarized much of this work.5,75... 

Cycloadditions of iminium compounds with 1,3-dienes to afford Diels-Alder adducts seems to be a reaction of general applicability.46 On the other hand, simple electron-rich imino species are less reliable dienophiles. Some electron-rich imines will undergo Diels-Alder reactions under acid catalysis and thus are probably actually reacting as iminium salts. However, inverse electron demand [4 + 2] cycloadditions of neutral imines with electron-deficient dienes have been reported, as have additions to exceptionally reactive dienes (vide infra). 

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