More Complex -Cycloadditions

Cycloaddition of species with triple bonds, which should logically be addressed at this point, will be postponed to later chapters. The reluctance of acetylene to dimerize to cyclobutadiene (CBD) on the ground-state surface follows directly from Fig. 6.2. It is sufficient to note that when two acetylene molecules approach one another in the plane-rectangular (D2/1) orientation, the two additional tt orbitals in acetylene are retained as such in CBD, so they cannot alleviate the forbiddenness of the [ 2g + pathway [5, Fig. 4]. Discussion of the reaction between dioxygen and acetylene to form 1,2-dioxetene and the cycloreversion of tetraalkyl-l,2-dioxetanes to two ketonic fragments has to be postponed until the relation between space and spin symmetry has been introduced in Chapter 9. 

The rest of this chapter is devoted to an examination of how [ 2 -f 2]-cycloaddition and [ r2 + 2]-cycloreversion are affected by the presence of additional multiple bonds that remain intact after the reaction has occurred, and of heteroatoms that - at first sight - play no apparent role in the reaction. 

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A more complex cycloaddition type is observed when diphenyl cyclopropenone and its thio analogue are reacted with the pyrylium betaine 451276 and the products obtained were assigned structures 450 and 452, respectively. 

The importance of the 1,3-dipolar cycloaddition reaction for the synthesis of five-membered heterocycles arises from the many possible dipole/dipolarophile combinations. Five-membered heterocycles are often found as structural subunits of natural products. Furthermore an intramolecular variant makes possible the formation of more complex structures from relatively simple starting materials. For example the tricyclic compound 10 is formed from 9 by an intramolecular cycloaddition in 80% yield ... 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

Other sporadic examples of [2 + 2] cycloadditions of olefins on the exo double bond of structurally more complex MCPs, such as methylenecyclo-propenes, allylidene-, and alkenylidenecyclopropanes, have been reported. Thus, dicyclopropylideneethane (2) reacted with TCNE (131) to give the [2 + 2] adduct 164 as a minor product, together with the prevalent [4 + 2] adduct 163 (Scheme 76) [39], The same reaction in a different solvent had been previously reported to furnish exclusively the Diels-Alder product (see Sect. 2.1.2) [5]. 

In contrast, with the calicene 230 TCNE is attached to five- and three-membered rings in a more complicated cycloaddition mode giving rise to 496s With a series of other calicenes no cycloaddition, but formation of stable charge-transfer complexes was observed2 93 ... 

The observation that the transition state volumes in many Diels-Alder reactions are product-like, has been regarded as an indication of a concerted mechanism. In order to test this hypothesis and to gain further insight into the often more complex mechanism of Diels-Alder reactions, the effect of pressure on competing [4 + 2] and [2 + 2] or [4 + 4] cycloadditions has been investigated. In competitive reactions the difference between the activation volumes, and hence the transition state volumes, is derived directly from the pressure dependence of the product ratio, [4 + 2]/[2 + 2]p = [4 + 2]/[2 + 2]p=i exp —< AF (p — 1)/RT. All [2 + 2] or [4 + 4] cycloadditions listed in Tables 3 and 4 doubtlessly occur in two steps via diradical intermediates and can therefore be used as internal standards of activation volumes expected for stepwise processes. Thus, a relatively simple measurement of the pressure dependence of the product ratio can give important information about the mechanism of Diels-Alder reactions. 

Moving on to vinylallene (2) and its derivatives as substrates, the situation becomes rapidly more complex - and more interesting. The possibility of using vinylallenes as diene components in Diels-Alder additions was recognized many years ago [5]. As shown in Scheme 5.44, the [2+ 4] cycloaddition of a generalized dienophile 283 to 2 yields 3-methylencyclohexene adducts 293. 

A tremendous number of transformations of allenes have been reported owing to their high jt-coordination ability towards transition metals. Among them, intramolecular cycloaddition reactions of allenes, in particular, appear to be a practical means of carbon-carbon bond formation in a complicated system. The allenic moiety, however, should be precisely designed for the synthetic purpose of more complex frameworks. A formidable challenge is the synthesis of diversely functionalized allenes of high chemical and/or enantiomerical purity. 

Our initial studies focused on the transition metal-catalyzed [4+4] cycloaddition reactions of bis-dienes. These reactions are thermally forbidden, but occur photochemically in some specific, constrained systems. While the transition metal-catalyzed intermole-cular [4+4] cycloaddition of simple dienes is industrially important [7], this process generally does not work well with more complex substituted dienes and had not been explored intramolecularly. In the first studies on the intramolecular metal-catalyzed [4+4] cycloaddition, the reaction was found to proceed with high regio-, stereo-, and facial selectivity. The synthesis of (+)-asteriscanoHde (12) (Scheme 13.4a) [8] is illustrative of the utihty and step economy of this reaction. Recognition of the broader utiHty of adding dienes across rc-systems (not just across other dienes) led to further studies on the use of transition metal catalysts to facilitate otherwise difficult Diels-Alder reactions [9]. For example, the attempted thermal cycloaddition of diene-yne 15 leads only... 

The reaction protocol was further extended to the concise synthesis of poly-oxamic acid, the unique polyhydroxyamino acid side-chain moiety of the antifungal polyoxin antibiotics (63). Treatment of the template 205 under standard thermal cycloaddition conditions with (5)-glyceraldehyde acetonide led to the formation of a single diastereoisomer 208 in 53% yield. Subsequent template removal released polyoxamic acid 209 in essentially quantitative yield. This represents a matched system, with the mismatched system leading to more complex reaction mixtures (Scheme 3.70). 

The stereochemistry of 1,3-dipolar cycloadditions of azomethine ylides with alkenes is more complex. In this reaction, up to four new chiral centers can be formed and up to eight different diastereomers may be obtained (Scheme 12.4). There are three different types of diastereoselectivity to be considered, of which the two are connected. First, the relative geometry of the terminal substituents of the azomethine ylide determine whether the products have 2,5-cis or 2,5-trans conformation. Most frequently the azomethine ylide exists in one preferred configuration or it shifts between two different forms. The addition process can proceed in either an endo or an exo fashion, but the possible ( ,Z) interconversion of the azomethine ylide confuses these terms to some extent. The endo-isomers obtained from the ( , )-azomethine ylide are identical to the exo-isomers obtained from the (Z,Z)-isomer. Finally, the azomethine ylide can add to either face of the alkene, which is described as diastereofacial selectivity if one or both of the substrates are chiral or as enantioselectivity if the substrates are achiral. 

This method constitutes a convenient synthesis of substituted tricyclo[2.2.0.02,6]hexane derivatives. It is surprising that the ring strain associated with these derivatives would permit their preparation at such high temperatures. A homologous reaction involves the intramolecular [2 + 2] cycloaddition of 2-vinylphenyl substituted cyclopropenes 5 which give benzotricy-clo[3.2,0.02,7]heptenes 6.74 This reaction also proceeds by sensitized photolysis but gives a more complex mixture. 

Ab initio molecular orbital calculations, coupled with activation energies and entropies from experimental data, have been employed to determine the nature of the intermediates in the reaction of singlet oxygen with alkenes, enol ethers, and enamines.214 Allylic alkenes probably react via a perepoxide-like conformation, whereas the more likely pathway for enamines involves a zwitterionic cycloaddition mechanism. The reactions of enol ethers are more complex, since the relative stabilities of the possible intermediates (biradical, perepoxide, and zwitterionic) here depend sensitively on the substituents and solvent polarity. 

Reactions of 59 with less hindered azides can be more complex. With trimethylsilyl azide, the isolated product was the azidosilane 73. The formation of 73 can be rationalized, however, as proceeding through the initial formation of a silanimine, followed by addition of MesSi—N3 across the Si=N double bond, as shown in equation 110. When 59 was treated with 1-adamantyl azide, the product was the silatetrazoline 74. Once again this product may have resulted from initial formation of a silanimine, followed in this case by 2 + 3 cycloaddition of the azide to the Si=N double bond (equation 111)98 148. 

This intuitive parallel can be best demonstrated by the example of electrocye-lic reactions for which the values of the similarity indices for conrotatory and disrotatory reactions systematically differ in such a way that a higher index or, in other words, a lower electron reorganisation is observed for reactions which are allowed by the Woodward-Hoffmann rules. In contrast to electrocyclic reactions for which the parallel between the Woodward-Hoffmann rules and the least motion principle is entirely straightforward, the situation is more complex for cycloadditions and sigmatropic reactions where the values of similarity indices for alternative reaction mechanisms are equal so that the discrimination between allowed and forbidden reactions becomes impossible. The origin of this insufficiency was analysed in subsequent studies [46,47] in which we demonstrated that the primary cause lies in the restricted information content of the index rRP. In order to overcome this certain limitation, a solution was proposed based on the use of the so-called second-order similarity index gRP [46]. This... 

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