Enediynes, photo-Bergman

SCHEME 8 Pyrene enediyne Photo-Bergman cyclization. 

This analysis confirms that the effect of cyclic constraints is not purely steric but also has an electronic component. Another aspect of this dichotomy is shown in Fig. 11 which illustrates the decrease in the energy gap between the frontier in-plane rc-MOs. The decrease in the C1-C6 distance destabilizes the occupied MO where the interaction between the end orbitals is antibonding and, at the same time, stabilizes the empty MO where the 7i -orbitals overlap constructively. As a result, the efficiency of the photochemical Bergman cyclization should increase and, indeed, the most efficient photo-Bergman cyclizations reported in the literature involve cyclic enediynes.43 Again, the analogy with interrupted [2 + 2] photocycloaddition is instructive. 

Jones, G. B., Russell, K. C. The photo-Bergman cycloaromatization of enediynes. CRC Handbook of Organic Photochemistry and... 

The diyne ene (84) undergoes photochemical cyclization on irradiation at 350 nm. The product obtained was identified as the phenanthrene derivative (85). " A variant of the photo-Bergman cyclization has been reported following the irradiation of the enediynes (86). The reactions are brought about using electron transfer from cyclohexa-1,4-diene in acetonitrile. This affords the products (87) in the yields reported under the structure. The products are formed by cyclization via the fulvene radical anion intermediate (88). " ... 

The development of photochemical variants of the Bergman cyclization would contribute to the broadening of its scope and utility. However there are relatively few examples of photoinduced cyclizations, despite the promise that such an approach would have in the photodynamic therapy of cancer. Funk and co-workers reported that certain cyclic ortho-dialkynylarenes, such as 9, underwent the photo-Bergman cyclization on irradiation in Pyrex. ° In 2000 Russell and co-workers showed that 10-membered cyclic pyrimidine enediynes could undergo cyclization efficiently (82-83%) when exposed to light (310 nm) in /-PrOH for 2-24 hours. 

Turro and co-workers showed that simple acyclic aromatic enediynes, such as 11, could also undergo Bergman cyclization under photochemical conditions. They proposed that the photo-Bergman cyclization of these substrates involved a diradical intermediate 2 identical to that of the thermal reaction."... 

Hirama and co-workers demonstrated that the photo-Bergman cyclization could be extended to both cyclic and acyclic aliphatic enediynes. 1,2-Dipropynylcyclopentene 13 in hexane was converted to indane derivative 14 in 71% yield when irradiated with a low-pressure mercury lamp at room temperature. 

Branda and coworkers provided another example of an acyclic enediyne that undergoes a photochemical reaction different from a photo-Bergman ring closure [21 ]. In this case, photochemical Bergman in strained enediynes is slower than photochromic bx-electrocychc ring closures. Only the latter process is observed upon UV (365 nm) excitation of the strained enediyne shown in Scheme 30.8. Branda and coworkers used the reversibility of this process for an on-demand uncaging of thermally reactive enediynes by visible light (>525 nm). 

SCHEME 30.8 Competition of photo-Bergman ring closure with hexatriene electrocyclization in photo-chromic enediynes. 

It was found that cyclization of benzannulated enediynes can be initiated by irradiation to give the same products as were obtained by thermal Bergman cyclization [238]. Photo-Bergman cyclization, which is also related to the chemistry of benzyne, has not been so extensively investigated. Terminal acyclic enediynes capable of cycloaromatization by thermal C -C route do not undergo photochemical initiation. However, introduction of one or two phenyl substituents in the acetylenic branches facilitates the C -C photocyclization of acyclic enediynes, but any increase in steric hindrance raises the activation barrier and the photochemical yield is significantly lower than in the case of their cyclic... 

Since DNA is the predominant target of the natural enediynes, a natural extension of the photo-Bergman lies in the development of efficient enediyne-based photonucleases. Based on their model studies. Funk and WiUiams designed both a phenanthrene and pyrene enediyne 49, which by virtue of the aminoalkyl side-chains had affinity for DNA (Scheme 13). ... 

SCHEME 14 Preparation and Photo-Bergman cyclization of phe-enediyne hybrid. 

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