3-Ene-l,5-diyne

Fig. 1 summarizes cyclizations of the two prototype molecules, (Z) hex-3-ene-l,5-diyne and (Z) hept-3,5,6-triene-l-yne. In all of these processes, bonds are formed from in-plane 7t-orbitals in the presence of an orthogonal 7i-system. However, it is clear that the properties of the newly formed cyclic conjugated systems can be quite... 

Fig. 16 (a) Comparison of potential energy profile for the formal Cope rearrangement of 3,4-difluorohexa-l,5-diyne-3-ene with that of (Z)-hexa-l,5-diyne-3-ene, (b) Rehybridization in the C(F) bond along the reaction path. EDI = 3,4-difluoro-hex- 3-ene-l,5-diyne ED2 = 1,6-di-fluoro-hex-3-ene-l,5-diyne BZY = difluoro-l,4-didehydrobenzezne TSBC = the transition state for the Bergman cyclization TSRBC = the transition state for the retro Bergman cyclization. 

Molecular scaffoldings with tetraethynylethenes (TEEs, 3,4-diethynylhex-3-ene-l,5-diynes) and trans-1,2-diethynylethenes [DEEs, (E)-hex-3-en-l,5-diynes] are at a particularly advanced stage.114,37 38 441 A collection of dose to one hundred partially protected and functionalized derivatives have been prepared in the meantime, providing starting materials for the perethynylated dehydroannulenes and expanded radialenes shown in Figure 6.136 441 TEEs and DEEs, as well as dimeric derivatives substituted at the terminal alkynes with donor (D, p-(dimethyl-... 

The coupling of an iodoalkene with a trimethylsilylacetylene and a subsequent desi-lylation result in the formation of 1,3-enynes with a terminal C=C triple bond. The parent acetylene usually does not react to give such an enyne under these reaction conditions, since Cu2C2 is formed. The solubility of this carbide is very low so that it precipitates. The very small amount of this copper species that remains in solution— if it couples at all—couples at both C atoms. Hence, the major coupling product then is the bis-coupling product of acetylene, a 3-ene-l,5-diyne, but in any case this product is formed only in small amounts because of the low solubility of Cu2C2. 

Paracyclophane-l, 5, 12, 16-tetrayne (37) was synthesized by Hopf via the reaction of dibromide 35 with Bu3SnSiMc3 (Scheme 10) [29]. The intermediacy of the novel cumulated para-quinodimethane 36 was invoked. Reaction of the ort/ o-substituted isomer 38 under the same conditions presumably gave the intermediate 39, which did not afford the corresponding orthocyclophane, but rather gave the highly strained 3,4-benzocyclooct-3-ene-l,5-diyne 40. 

The conversion of an ene-diyne 2.77 into a 1,4-benzenediyl diradical 2.78 on heating is known as the Bergmann reaction . The 1,4-aromatic radical 2.78 maybe converted into benzene or may react with CCI4 to givep-dichlorobenzene (2.79). Bergmann etal converted deuterium-labelled hexa-3-ene-l,5-diyne 2.80 on heating at 200°C into deuterium-labelled hexa-3-ene-l,5-diyne 2.81 in which both deuterium atoms were shifted from the terminal acylene positions to vinyl positions at the interior of the chain. 

The Ni-catalyzed cross-coupling reaction of alkynyl Grignard reagents 60 with ( )- or (Z)-dichloroethene 61a,b has been applied to a simple procedure for the preparation of the protected fomi 62a,b of a highly unstable synthon, as hexa-3-ene-l,5-diyne [Eq. (23). Separation of the diastereomers 62a and 62b is facile since the former is an oil and the latter is a solid [35]. 

Elimination of sulfonic acids. Double bonds can be introduced into organic molecules by elimination of sulfonic acids from the corresponding sulfonic acid esters. The reaction proceeds particularly smoothly using DBN or DBU as reagent. Thus, treatment of 3-tosyloxyhexa-l, 5-diyne (10) with excess DBN in ether at room temperature (1 hr.) affords a 40 60 mixture of cis- and fra s-hex-3-ene-l,5-diyne (11 70%).2... 

The key transformation of 3-ene-l,5-diynes is a thermal rearrangement that was disclosed in the early 1970s by Darby et al. and Lockhart and Bergman, and which is commonly called the Bergman cycloaromatization (Scheme 19.3). In the classical Bergman experiment, the deuterated enediyne 6 was transformed into the isomer 7 or, in the presence of a hydrogen donor, into deuterated benzene 9. This reaction is believed to proceed through a diradical benzenoid species (a 77-benzyne). ... 

Acyclic Z 3-ene-l,5-diynes, such as 6, undergo the classical Bergman thermal cycloaromatization only at elevated temperatures (a photochemical promoted Bergman-type cycloaromatization of acyclic enediynes can take place under milder conditions on particular substrates). However,... 

When the double bond of the 3-ene-l,5-diyne system is part of a benzene or a naphthalene ring, a lowered activity resulted, in agreement with the lower activity of benzo-fused enediynes already cited in Section 19.3.2. Finally, the activity both in vitro (human carcinoma KB cells) and in vivo (mice inoculated with murine P338 leukemia) of 87-89 was tested. Interestingly, while the phenyl carbamates have no detectable in vitro activity against plasmid DNA and were less cytotoxic in vitro than 87-89, an opposite behavior was observed in vivo. Thus the phenyl carbamates showed an interesting activity, while the sulfones showed little or no activity, probably due to the fact that they are quite unstable and they are not able to reach tumor cells before cycloaromatization begins. 

Hexadehydro-[ 18]annulene 80>, 15, (see Table 4) possesses no inner protons and the six equivalent outer protons resonate at t 2.98. This represents a downfield shift of over 1 ppm from a model compound, cis-hex-3-ene-l,5-diyne, 9, (t 4.11). This model compound also served to clarify the interpretation of the singlet at t 5.55 in the case of l,5,9-tridehydro-[12]annulene, 1, a molecule for which aromaticity is not predicted. The downfield shift of 15 and the upfield shift of 1 from the acyclic model can then be attributed to a diamagnetic ring current in 15 and a paramagnetic ring current in 1. 

Bergman and coworkers initially studied the cyclization of enediynes more than two decades ago [5, 33], The parent compound of these systems, (Z)-hex-3-ene-l,5-diyne (100) cyclizes at elevated temperatures to afford the 1,4-didehydrobenzene diradical 6 (Fig. 8). 

Coupling reactions. The hexacarbonyldicobalt complexes of cycloocta-l,5-diynes and cyclooct-3-ene-l,5-diynes have been acquired by reductive cyclization of the dication... 

Bis-(4,4-ethylenedioxycyclohexyl)hexa-l,5-diyne-3,4-diol (mixture of isomers) in abs. pyridine added dropwise at room temp, to diphosphorus tetraiodide in GS2, stirred 2 hrs. at room temp., then GS2 removed by distillation during 1 hr. fran5-3,4-bis-(4,4-ethylenedioxycyclohexyl)hex-3-ene-l,5-diyne. Y 43%. H. Inhoffen et al., A. 884, 24 (1965). 

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