Cis-enediynes

The route to the cis-enediyne 32 a starts from cis-2,3-dichloro-2-buten-l,4-diol, which is obtained by exhaustive reduction of mucochloric acid (Scheme 13-8) [45]. The two dibromo-methylene residues in 36, the direct precursor to 32 a, are introduced sequentially in a synthetic route which includes as the key step the selective reduction of orthoester 33 to the monopro-tected diol 34. Since compound 35 and all other intermediates with dibromomethylene groups... 

Bicyclic cis- and frans-isoxazolidinyldiynes have been prepared by intramolecular nitrone cycloaddition of the two side chains of an acyclic enediyne-nitrone precursor (Scheme 2.233) (731). 

Scheme 4. Proposed mechanism for electrochemical cis-trans isomerization of enediyne 16 [27].

Bisethynylation of yK-dtcfitorotthyleite i. Enediynes can be prepared by the palladium-catalyzed coupling of terminal alkyncs Uiilb vic-dkhlorocthylcncs, particularly with the cis-tsomer (equation 1). 

The instability of the enediyne-containing dynemicin model compounds in which the epoxide had been opened prompted Nicolaou et al. to seek a means by which they could tame the reactivity of the cis-diois sufficiently to observe them (253, 254]. By comparing the resonance energies of benzene (36 kcal/mol), naphthalene (61 kcal/mol) and anthracene(84 kcal/mo ) it was reasoned that there would be less of a driving force for cycloaromatization of the diols 346 and 347 compared with 345 (Scheme 7-73). Indeed, treatment of 343 and 344 with silica... 

Enyne metathesis/metallotropic [l,3]-shift domino processes are also valuable for natural product synthesis [33c,d]. Reaction of substrate 168 with cis-l,4-diacetoxy-2-butene in the presence of Grubbs catalyst 2 generated the intermediate ruthenium alkinyl carbene through a relay RCM with the hberation of 2,5-dihydrofuran followed by metallotropic [l,3]-shift and terminating (Z)-selective CM with the co-olefin to yield the conjugated enediyne 169 (Scheme 2.58) [33c]. The antitumor active Panax ginseng constituent (3R,9R,10R)-panaxytriol was readily synthesized from 169 in six steps. 

In the absence of the competing coordination with arene, the Ru- and Fe-catalyzed reactions of nonbenzannelated enediynes proceed quickly and efficiently, although photochemical liberation of the arene ligand occurs more effectively with Fe due to its lower arenophihcity relative to ruthenium (Scheme 30.18). Facile photochemical dissociation of the prodnct-metal complexes can be used for the creation of catalytic cycles. A fascinating feature of this approach is that it allows incorporation of trans/cis isomerization in the catalytic cycle. The possibihty of using trans enediynes in cycloaromatization reactions has the potential of dramatically increasing the scope of these reactions. 

Figure 5. Final domain assignments of nine-membered enediyne PKSEs from C-1027producer S. globisporus and the NCSproducer S. carzinostaticus. Active site serines within ACP domains arephosphopantetheinylated by PPTdomain (in cis) followed by production of the polyene precursor to the enediyne core. R, 3, 5 -adenosine diphosphate.

Konig, B., Schofield, E., Bubenitschek, P. and Jones, P.G. (1994) Synthesis and photoinduced cis-trans isomerization of diaryl enediyne chromophores. Journal of Organic Chemistry, 59(23), 7142-7143. 

Reaction between substituted alkyne (1 eq. each) and cis-dichloroethylene (1 and 0.5 eq.), under catalytic amount of Pd(PPh3)4, Cul and -BuNH2 in benzene give chloro-en-yne precursors (60-62% and 6-8%, respectively) and symmetrical enediyne (9-13% and 61-65%, respectively). This reaction was completed in 3-5 min under microwave exposure. 

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