Cycloaddition reactions conjugated dienes

Beyond dimerization and oligomerization, [2 + 2]- and [4+ 2]-cycloadditions with conjugated dienes and styrenes and the addition of nucleophiles are typical reactions of strained cyclic allenes. These transformations have been studied most thoroughly with 1,2-cyclohexadiene (6) and its derivatives [1, 2]. Concerning the cycloadditions, a theoretical study had the surprising result that even the [4+ 2]-cycloadditions should proceed in two steps via a diradical intermediate [9]. In the case of nucleophiles, the sites of attack at several 1,2-cyclohexadiene derivatives having an... 

Trifluoroethene has been reported to undergo cycloadditions with conjugated dienes to give both [2 + 2] and [4 + 2] cycloadducts.25 Although mixtures of regio- and stereoisomeric cyclobutanes are obtained in these cases it still constitutes a synthetically useful reaction. 

The third important reaction of singlet oxygen is 1,4-cycloaddition to conjugated dienes, resulting in the formation of endoperoxides.360-364,371 -373 Acyclic dienes give monocyclic endoperoxides that exist in rapidly equilibrating half-chair conformations 410,411... 

Let us consider, for example, the origin and evolution of the well-known Diels-Alder reaction. The net outcome of this process is the cycloaddition of conjugated dienes with alkenes, leading to the formation of cyclohexene derivatives (Scheme 2.7). Isolated examples of this cycloaddition, for example... 

Much attention has been directed to the chemistry of p-heteroatom-substituted allylic cations (5), especially oxyallyl cations (7), from both synthetic and mechanistic viewpoints. One of the characteristic reactions of oxyallyls (7) is their [4 -i- 3] 7 cycloadditions with conjugated dienes, which provide a... 

Cycloadditions of conjugated dienes to alkenes (dienophiles) provide rapid access to substituted cyclohexenes. In view of the widespread occurrence of carbocyclic compounds in nature, and the recent demands for the synthesis of enantiomerically pure compounds, it is not surprising that carbohydrates were examined as substrates for Diels-Alder reactions. Both carbohydrate-derived dienophiles and dienes have been described in the literature. The products of reactions involving these types of compounds, referred to as annulated sugars, are most often formed stereoselectively. The hi levels of both diastereofacial selectivity and endo/exo selectivity sometimes result in the formation of a single cycloadduct from among several possibilities. 

This chapter will focus on the development of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes (Scheme 4.1) [3]. 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

The Basic Mechanisms of Cycloaddition Reactions of Carbonyl Compounds with Conjugated Dienes... 

The cycloaddition reactions of carbonyl compounds with conjugated dienes cannot be discussed in this context without trying to understand the reaction mechanistically. This chapter will give the basic background to the reactions whereas Chapter 8 dealing with theoretical aspects of metal-catalyzed cycloaddition reactions will give a more detailed description of this class of reactions, and others discussed in this book. 

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

The enantioselective cycloaddition reaction catalyzed by chiral BOX-copper(II) complexes has been used for conjugated cyclic dienes, e.g. 1,3-cyclohexadiene 5c, as shown in Scheme 4.21 [9, 32]. This cycloaddition reaction is dependent on sol-... 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

The Diels-Alder reaction,is a cycloaddition reaction of a conjugated diene with a double or triple bond (the dienophile) it is one of the most important reactions in organic chemistry. For instance an electron-rich diene 1 reacts with an electron-poor dienophile 2 (e.g. an alkene bearing an electron-withdrawing substituent Z) to yield the unsaturated six-membered ring product 3. An illustrative example is the reaction of butadiene 1 with maleic anhydride 4 ... 

Another reaction unique to conjugated dienes is the Diels-Alder cycloaddition. Conjugated dienes react with electron-poor aikenes (dienophiles) in a single step through a cyclic transition slate to yield a cyclohexene product. The reaction is stereospecific, meaning that only a single product stereoisomer is formed, and can occur only if the diene is able to adopt an s-cis conformation. 

In numerous synthetic studies,9" 6 100 it has been demonstrated that porphyrins react at the chromophore periphery in cycloaddition reactions, rearrangements, conjugative additions and substitution reactions to yield interesting porphyrin derivatives. Thus, metal-free protoporphyrin IX dimethyl ester reacts in Diels-Alder reactions108a b with dienophilcs like ethenetetra-carbonitrile and acetylenedicarboxylates at the diene structural parts to yield, according to the reaction conditions, the corresponding monoadducts 2 and 3 (see also Section 1.2.) and bisadducts 1 (see also Section 1.4.), respectively. 

The classical Diels-Alder reaction is a cycloaddition between a conjugated diene and a second component, called dienophile, which has at least a n bond (Equation 1.1). When one or more heteroatoms are present in the diene and/or dienophile framework, the cycloaddition is called a hetero-Diels-Alder reaction. 

Lopez J. C., Lukacs G. Pyranose-Derived Dienes and Conjugated Enals. Preparation and Diels-Alder Cycloaddition Reactions ACS Symp. Ser. 1992 494 33-49 Keywords carbohydrate, befera-Diels-Alder reactions, stereoselectivity... 

In the Diels-Alder reaction a double bond adds 1,4 to a conjugated diene (a 2 + 4 cycloaddition), so the product is always a six-membered ring. The double-bond compound is called a dienophile. The reaction is easy and rapid and of very broad scope and reactivity of dienes and dienophiles can be predicted based on analysis of the HOMOs and LUMOs of these species. Ethylene and simple alkenes make poor dienophiles, although the reaction has been carried out with these compounds. 

As applied to cycloaddition reactions the rule is that reactions are allowed only when all overlaps between the HOMO of one reactant and the LUMO of the other are such that a positive lobe overlaps only with another positive lobe and a negative lobe only with another negative lobe. We may recall that monoalkenes have two n molecular orbitals (p. 9) and that conjugated dienes have four (p. 36), as shown in Figure 15.1. A concerted cyclization of two monoalkenes (a 2 -f- 2 reaction) is not allowed because it would require that a positive lobe overlap with a negative lobe (Fig. 15.2). On the other hand, the Diels-Alder reaction (a 2 -f 4 reaction) is allowed, whether considered from either direction (Fig. 15.3). 

In its simplest form the Diels-Alder reaction is a cycloaddition reaction between a conjugated diene and alkene (dienophile). 

The Diels-Alder reaction is an organic chemical reaction (specifically, a cycloaddition) between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can also proceed if the alkene is replaced by an alkyne moiety or even if some of the atoms... 

The aqueous Diels-Alder reaction has also been used for bioconjugate studies. A Diels-Alder reaction of diene oligonucleotides with maleimide dieneophiles was used to prepare oligonucleotide conjugates in aqueous media under mild conditions (Eq. 12.39).102 A Diels-Alder-type cycloaddition of an electronically matched pair of saccharide-linked conjugated dienes and a dienophile-equipped protein was the... 

Cycloaddition of 2-cyanoalk-2-enones with several conjugated dienes proceeded under zinc chloride catalysis.636 Zinc halides have also shown reactivity with phenylacetylenes.637 Zinc chloride is an effective Lewis acid catalyst in the Diels Alder reactions of the keto esters and the effects on stereochemistry of catalysts used have been examined.638... 

The behavior of complexes of nitroalkenes (42) with LA toward conjugated dienes is yet another factor underlying the role of these complexes. Conjugated nitroalkenes (42) are considered as active dienophiles in classical Diels-Alder reactions (104, 105). On the contrary, in the presence of SnCl4, nitroalkenes (42) react with cyclopentadiene and 1,3-cyclohexadiene exclusively at one double bond (103). Therefore, it is highly probable that the 42 + 43 cycloaddition proceeds by a nonconcerted mechanism in the presence of LA (see Scheme 3.40). 

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