Patai S., Rappoport Z. 2000 The chemistry of functional groups. The chemistry of dienes and polyenes. V. 2 / 0329 479

(516)

V. [8 Y 2] CYCLOADDITION REACTIONS

The thermally allowed [8 C 2] cycloaddition reactions may be considered as the 10 analogs of the Diels –Alder reaction in which the diene component has been replaced by a tetraene component. Like trienes in the [6 C 4] cycloaddition reactions, the 8 tetraenes must satisfy certain requirements concerning geometry in order to be able to participate in an [8 C 2] cycloaddition. For example, tetraenes 518 and 519 can undergo an [8 C 2] cycloaddition, whereas an [8 C 2] cycloaddition with 520 is virtually impossible. Due to its fixed -system, 519 is more reactive in cycloaddition reactions than 518 and is therefore more often encountered in the literature. [8 C 2] Cycloadditions have been applied only

occasionally in organic synthesis. The reaction often proceeds with accompanying [4 C 2] and, in the case of a diene being the tetraenophile, [6 C 4] cycloaddition reactions.

Nair and coworkers have described the [8 C 2] cycloaddition reactions of 2H-cyclohep- ta[b]furan-2-ones such as 521 in several reports311. The reactions of 521 with alkenes yield azulene derivatives upon extrusion of carbon dioxide. Table 30 summarizes the results of

CO2Et

CO2Et

(151)

+

R1

R2

CO2Et

O O

(524)

When cycloalkyl pentafulvenes 522e–g were employed, [8 C 2] and [4 C 2] cycloadducts were produced in approximately equal amounts. The [4 C 2] cycloadduct became the major cycloadduct in the reaction of 521 with 6,6-diphenylfulvene 522d. Semi-empirical

TABLE 30. Yields of products in the reaction of 521 with 522

OMe

+

(534)

(209)

H

N

NCCN

(549)

VI. [2 Y 2 Y 2] CYCLOADDITION REACTIONS

Even more than [6 C 4] and [8 C 2] cycloaddition reactions, the [2 C 2 C 2] cycloaddition reactions require a very well preorganized orientation of the three multiple bonds with respect to each other. In most cases, this kind of cycloaddition reaction is catalyzed by transition metal complexes which preorientate and activate the reacting multiple bonds111,324. The rarity of thermal [2 C 2 C 2] cycloadditions, which are symmetry allowed and usually strongly exothermic, is due to unfavorable entropic factors. High temperatures are required to induce a reaction, as was demonstrated by Berthelot, who described the synthesis of benzene from acetylene in 1866325, and Ullman, who described the reaction between norbornadiene and maleic anhydride in 1958326. As a consequence of the limiting scope of this chapter, this section only describes those reactions in which two of the participating multiple bonds are within the same molecule.

Most metal mediated [2 C 2 C 2] cycloadditions involve two triple bonds which coordinate to a metal center to form a reactive metallocyclopentadiene species (vide infra). The corresponding reactions involving at least two double bonds and an intermediate metallocyclopentane species are almost completely limited to norbornadiene systems. These reactions can be considered as homo Diels –Alder reactions.

The most efficient catalysts for the homo Diels –Alder reactions of norbornadiene were found to be cobalt327 and nickel328 complexes. The general mechanistic pathway that has been proposed for these reactions has been depicted in equation 161329. According to this mechanism, co-ordination of norbornadiene and the olefin or acetylene to the metal center gives 557, which is in equilibrium with metallocyclopentane complex 558. Then, insertion of the olefin or acetylene in the metal – carbon bond takes place to form 559. Reductive elimination finally liberates the deltacyclane species.

(161)

(559)

Lautens and colleagues328 found 5 mol% Ni(COD)2/2PPh3 to be the most efficient catalytic system for the cycloaddition between methyl vinyl ketone (100) and norbornadiene (560). The adducts 561 and 562 were obtained with 99% overall yield and with an exo/endo ratio of >95/<5 (equation 162).

Unlike thermal homo Diels –Alder reactions in which endo adducts predominate330, the nickel catalyzed reactions of acyclic electron-deficient dienophiles afford the exo isomers as the major cycloadducts. This has been explained by unfavorable steric interactions within intermediate 559 leading to the endo adduct. Cyclic dienophiles, on the contrary, give predominantly the endo isomer, which has again been explained by unfavorable steric interactions within exo 559. The preferred conformation of the dienophile, s-cis or s-trans, has also been suggested to play a role328.

The regiochemistry of nickel mediated cycloadditions of substituted norbornadienes has been investigated in detail. The regioselectivity, exo/endo selectivity and site selectivity seem to depend strongly on the substituents on both diene and dienophile. Tetracyanoethene, for example, reacted with 2-acetyloxymethyl substituted norbornadiene on the distal side331.

The reactions between norbornadiene 563 and unsymmetrical dienophiles can, in principle, produce up to 8 cycloadducts. Lautens and colleagues328 reported that 564 was the main regioisomer found in the reactions of 563 with the range of dienophiles examined (equation 163, Table 32). When the PPh3 ligand was replaced by P(OPr-i)3, however, 566 became the main product in the reaction of 563 with methyl vinyl ketone. The endo/exo selectivity depended strongly on the olefinic substituent and the regiochemical course of the reaction. The reaction of methyl vinyl ketone with 2-methoxynorbornadiene, which proceeded more slowly than the reaction with 563, gave the regioisomer analogous to 566 as the major isomer, whereas the reaction with 2-trimethylsilylnorbornadiene afforded the adduct analogous to 565 as the major product. An adduct analogous to 567 was not obtained in any instance.

[2 C 2] Adducts were obtained as exclusive adducts or as by-products in the nickel mediated reactions of some substituted norbornadienes with various dienophiles. The formation of these products was considered to result from an intermediate metallocyclopentane species built up of the metal center, the dienophilic double bond and one of the double bonds of the norbornadiene moiety.

The cobalt mediated homo Diels –Alder reaction of norbornadiene (560) with phenyl acetylene (568a), affording a phenyl substituted deltacyclene, demonstrated the potential of low-valent cobalt complexes as catalysts332. Lautens and coworkers327 extended the scope of this reaction and were able to synthesize a wide range of substituted deltacyclenes from alkynes 568 (equation 164, Table 33). The low-valent cobalt(I) or cobalt(0) species to be used was prepared in situ by reduction of Co(acac)3 with Et2AlCl. Monosubstituted