Enediynes, cross-conjugated

Scheme 5 Thermal and reductive cyclizations of cross-conjugated enediynes.

Various cross-conjugated enediynes undergo Bergman-type cycloaromatizations upon reduction with potassium metal, generating anions of fulvenes and fulvalene derivatives (Scheme l).6 Not all cross-conjugated enediynes yield cyclized dianions upon reduction some give uncyclized, Y-shaped, cross-conjugated dianions, whereas others apparently yield radical anions that either dimerize or persist as monomers. 

The main use of this reaction is for the synthesis of bowl-shaped polycyclic aromatic hydrocarbons and fullerenes [325], Exploring the boundaries of these reactions resulted in the synthesis of compounds of different geometry, tt-electron structure, aromaticity, and with the presence of heteroatoms [324]. Various cross-conjugated enediynes exert anionic cycloaromatization to form fulvene and fulvalene anions and even heterocycles. In accordance with the concept of aromaticity, the anionic Bergman type cyclization is preferred to the classical Bergman cycloaromatization of linear enediynes. This anionic cyclization differs considerably from the classical Bergman cyclization and related cycliza-tions, as well as from other dianionic cyclizations [326]. 

The enediyne units play an important role in the structure of various organic molecules. There are three possible isomers (Z)-5.992, ( )-5.993, and gem-5.685. 1,2-Diethynylethene (Z-3-hexene-l,5-diyne) (Z)-5.992, on the one hand, represents a promising structural unit for the synthesis of potential anticancer agents in medicine, which this review reflects. On the other hand, ( -3-hexene-l,5-diyne) (E)-5.993 unit is redox-active and is used as a chromophore for developments in materials chemistry [454-457]. Several instances of redox-active chro-mophores that have new structures with an azulene core have applications in the electrochromic materials area (Figure 5.1) [457]. The cross-conjugated enediyne gem-5.685 unit is rarely used but it is possible to use... 

Treitel, N., Eshdat, L., Sheradsky, T., et al. (2006) Reductive Bergman-type cyclizations of cross-conjugated enediynes to fulvene and fulvalene anions the role of the substituent. Journal of the American Chemical Society, 128(14), 4703-4709. 

Eshdat, L., Berger, H., Hopf, H. and Rabinovitz, M. (2002) Anionic cyclization of a cross-conjugated enediyne. Journal of the American Chemical Society, 124(15), 3822-3823. 

Related steps, leading to unusual cross-conjugated systems, were discussed for the isomerization ( )-enediynes [78]. 

The Pd-catalyzed homocoupling of tenninal alkynes with (Z)-l,2-dichloroethylene furnishes the corresponding (Z)-conjugated enediynes, whose structural feature is encountered in a class of antitumor antibiotics and is the object of current intense synthetic and mechanistic studies. " Unsymmetrical (E)- and (Z)-enediynes are prepared in a one-pot procedure by two sequential Pd-catalyzed cross-coupling reactions of (E)- and (Z)-l,2-dichloroethylene with the appropriate l-alkynes. Reduction of enediynes A with a zinc copper-silver couple in aqueous methanol provides access to (Zj-trienes. " ... 

Linear Z-enediynes having a diethynylethene fragment with six jt-electrons, usually cycloaromatize by the Bergman mode, while the cross-conjugated diethynylethenes 3.685 are incapable of aromatization because the fulvene diradical formed has only five ir-electrons in the ring (Scheme 3.71A) [324]. 

In this analysis, the activation barrier for both C1-C6 and C1-C5 cyclizations of enediyne radical-anions can be described as the avoided crossing between the out-of-plane and in-plane MOs (configurations). One-electron reduction populates the out-of-plane LUMO of the enediyne moiety. At the TS (the crossing), the electron is transferred between the orthogonal re-systems to the new (in-plane) LUMO. This effect leads to the accelerated cyclization of radical-anions of benzannelated enediynes, a large sensitivity of this reaction to re-conjugative effects of remote substituents and the fact that this selectivity is inverse compared to that of the Bergman cyclization. Similar electronic effects should apply to the other reductive cyclization reactions that were mentioned in the introduction. 

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