Enediynes, nucleophilic additions

The first issue confronted by Myers was preparation of homochiral epoxide 7, the key intermediate needed for his intended nucleophilic addition reaction to enone 6. Its synthesis began with the addition of lithium trimethylsilylacetylide to (R)-glyceraldehyde acetonide (Scheme 8.6).8 This afforded a mixture of propargylic alcohols that underwent oxidation to alkynone 10 with pyridinium dichromate (PDC). A Wittig reaction next ensued to complete installation of the enediyne unit within 11. A 3 1 level of selectivity was observed in favour of the desired olefin isomer. After selective desilylation of the more labile trimethylsilyl group from the product mixture, deacetalation with IN HC1 in tetrahydrofuran (THF) enabled both alkene components to be separated, and compound 12 isolated pure. 

Fiirstner and co-workers have demonstrated the utility of the PtCl2-catalyzed carboalkoxylation of protected o-alkynyl phenols in the synthesis of the pterocarpene nucleus of erypoegin H <2007AGE4760>. Naphthalene fused 2,3-dihydrofurans have been shown to be available through a Pt- and Ru-catalyzed aromatization of enediynes with concomitant intramolecular nucleophilic additions <2007S2050>. 

Ru(Tp)(PPh3)(MeCN)2]PFg has been employed as catalyst to produce l-iodo-2-naphthol in DMF and 2-iodobenzo[d]oxepin in benzene from l-(2/-iodoethynylphenyl)-2-propyloxirane. The solvent-dependent chemoselectivity has been ascribed to a solution equilibrium between ruthenium-Tt-iodoalkyne and ruthenium-2-iodovinylidene intermediates.66 The same ruthenium phosphine complex has been efficiently employed as catalyst in the nucleophilic addition of water, alcohols, aniline, acetylacetone, pyrroles, and dimethyl malonate to unfunctionalized enediynes that yielded functionalized benzene products in good yields (Fig. 8.6).67 [Ru(Tp)-(PPh3)(MeCN)2]PFg has been also found very active in catalytic benzannulation of l-phenyl-2-ethynylbenzenes in dichloroethane to afford phenanthrene.68... 

Fig. 8.6. The nucleophilic addition of water, alcohols, pirroles, and Hacac to unfunctionalized enediynes yields functionalized benzene derivatives.

Activation of acyclic enediynes by ruthenium-catalyzed nucleophilic aroma-tization has also been reported (396). The importance of this cyclization is indicated by the regioselectivity of nucleophilic addition, which occurs only at... 

In the attempt to unravel the biosynthetic origin of sporolides, and considering that these compounds are composed of a chlorinated cyclopenta[a]indene ring and a cyclohexenone moiety, it was hypothesized that the former fragment could be nonenzymatically derived from an unstable nine-membered enediyne precursor by the nucleophilic addition of chloride. Support to this suggestion came from sequence analysis of S. tropica CNB-440 genome, which led to the identification of two biosynthetic loci encoding enediyne PKSs. Analysis of the respective... 

Nucleophilic Addition to a Pstra-benzyne Derived from an Enediyne A Mechanism for Incorporating Halide into Biomolecules... 

Perrin, C.L., Rodgers, B.L. and O Connor, J.M. (2007) Nucleophilic addition to a p-benzyne derived from an enediyne a new mechanism for halide incorporation into biomolecules.of the American Chemical Society, 129(15), 4795-4799. 

Since allylsilane can be considered as a very soft nucleophile because of the involvement of o-7i conjugation between the -electrons of the double bond and the o-electrons in the carbon-silicon bond, the addition of allylsilanes to ,/3-unsaturated enone moiety occurs exclusively via 1,4-addition19,20. A typical Sakurai-Hosomi reaction is illustrated in the reaction of allylsilane 66 with enone 67 in the presence of TiCU to give 68 which is used for the synthesis of a cyclic enediyne (equation 45)108. A similar reaction has been used for the synthesis of ewf-herbasolide 70 from enone 69 (equation 46)109. Prenylsilane undergoes 1,4-addition with squaric acid chloride 71 followed by dechlorosilylation to give 72 as the predominant product (equation 47). Interestingly, other simple allylsilanes react in a 1,2-addition fashion to yield 73110. 

Scheme 21.17) [25]. Odedra et al. reported the addition of nucleophiles in the ruthenium-catalyzed cycloaromatization of conjugated enediynes 41, where functionalized benzene and naphthalene derivatives 42 were obtained with high... 

Another pathway, which does not require activation, is based on nucleophilic halide anion attack on an enediyne to afford the aryl halide [335]. Thus, cyclodeca-l,5-diyne-3-ene 3.720 in the presence of lithium halide and a weak acid produces 1-halotetrahydronaphthalene 3.723. Kinetic data show that the rate determining step of the cyclization is the formation of para-henzyne diradical 3.721. Then fast addition of halide anion occurs leading to the generation of the haloaryl anion 3.722, X = Cl, Br, I, or the corresponding aryllithium, which is protonated to form 1-halogenated 5,6,7,8-tetrahydronaphthalene 3.723 (Scheme 3.81). 

---