The synthesis of several polycyclic compounds 1a-c, 2, and 3 has been performed through a tandem Stille/[4 + 2] cascade reaction from cyclic bis(enoltrifluomethanesulfonate) 4a-c, 5, and 6, respectively. The reaction proceeds very efficiently in a one-pot operation at roomtemperature in DMF in the presence of a catalytic amount of Pd(CH(3)CN)(2)Cl(2) and LiCl.[reaction: see text]
The new dienediynes 5, 6, and 7 were synthesised from a monoprotected diyne and an already described bis(eno1 triflate) 4 derived from formylcyclopentanone. When 5 and 6 were subjected to nucleophilic attack by a thiol, cycloaromatisation occurred, and the phenanthrenes 23a and 23b were obtained in 30 and 42 % yield, respectively.The neocarzinostatine chromophore"] 1, isolated from Streptomices neocarzinostaticus by Ishida[*], shows an extraordinary cytotoxic activity against a number of cancer cells"]. This cytotoxicity is due to the presence of a very strained bicyclo[7.3.0] system which after activation by treatment with a thiol and formation of a very unstable eneyne cumulene 2 undergoes cycloaromati~ation[~] via the radical species 3a. The diradical thus formed is capable of abstracting protons from DNA, thus causing destruction of the cancer cell. After uptake of two hydrogen atoms the unstable species 3a gives the non-active aromatic product 3b. From a synthetic point of view, complex methods were proposed for the construction of highly strained mediummembered ring structure^ [^]. We focused our attention on a straightforward and easy access to the bicyclic[8.3.0] system of the type 5, 6, and 7. Analogues with a medium ring structure containing 10 atoms were chosen in order to obtain compounds which are more stable than the natural labile core 1 but are still susceptible to cycloaromatisation.In a preliminary communication [6] we proposed the use of the bis(eno1 triflate) 4 to have rapid and efficient access to compound 5. In this paper we report in detail on the complete synthesis of compound 5 as well as two new analogues 6 and 7. Analogues containing (E) and (2) acyclic dienediyne systems have so far been prepared by our group starting from 4L71. Compound 4 was prepared by reaction of the lithium enolate 9 of the formylcyclopentanone 8 with triflic anhydride. Sulfonation occurred selectively at the former formyl oxygen atom. The monotriflate 10, due to its instability, was converted after rapid flash chromatography on silica gel into bis(eno1 triflate) 4 in 45% yield.In order to study the effect of aromatic substitution and the position of the aromatic moiety on the [8.3.0]bicyclic core, we decided to synthesise the starting diynes 13a and 13b. The synthesis started with a Pd(O)/Cu(I)-catalysed coupling reaction of 2-bromobenzaldehyde with (trimethylsily1)acetylene affording the known aldehyde 11 a ['] in 94%
Reaction of (E/Z)-1-bromopropene with exactly 1.42 equivalents of nBuLi followed by addition of water produces in situ a THF solution of propyne. Addition of a vinylic or aromatic halogenated substrates, Pd(PPh 3 ) 2 Cl 2 , CuI and an amine to this solution give high yield of the corresponding coupling product bearing a propyne moiety. This practical procedure avoids the use of expensive and inflammable propyne gas which need a special apparatus for bubbling it into the reaction flask.
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