Enediynes rearrangement

Another example of a zwitterionic product of a cycloaromatization reaction was given by Kerwin and coworkers. Their skipped (aza)enediynes rearranged to yield (aza)eneyne-allenes that subsequently cyclized under addition of methanol (in a byproduct), which is consistent with a partitioning between a diradical and a zwitterionic reaction pathway (Scheme 15).66... 

It is noteworthy that Jones and Darby, who pioneered the enediyne rearrangement, now known as the Bergman rearrangement, and Nicolaou, who achieved the first total synthesis of the enediyne antibiotic calicheamicin 7 / were under the joint supervision of Profs. Franz Sondheimer and Peter Garratt. It might seem that all researchers in the enediyne field have been influenced by Sondheimer and Garratt. 

SCHEME 1 Thermal enediyne rearrangements that give rise to cytotoxic biradicals. 

Upon heating the enediyne la rearranges reversibly to the 1,4-benzenediyl diradical 2a, which in its turn can rearrange to the enediyne lb or—in the presence of a hydrogen donor (e.g. cyclohexa-1,4-diene)—react to the aromatic compound 3a. 

A similar process involving an all-carbon cyclic system has also been investigated [59]. Other examples involving the prototropic rearrangement of enediynes having an imino or a keto substituent at the propargylic position to form the corresponding enyne-allenes have also been observed [60, 61]. 

Scheme 20.22 Synthesis of 11 H-benzo[fo]fluorenes via prototropic rearrangement of benzannulated enediynes.

Detailed thermochemical data for the Bergman rearrangement were determined by Roth et al. from gas-phase NO trapping experiments. The activation barrier for ring opening of 28 to enediyne (Z)-16 was reported as 19.8 kcal/mol, the enthalpy of formation of (Z)-16 293 = 129.5 kcal/mol) is lower than that of p-benzyne... 

Cycloaddition of cncdiynes. Photolysis of the enediyne 1 in the presence of catalytic quantities of CpCo(CO)2 in refluxing toluene results in the tricyclic diene 2. The reaction involves a diene rearrangement in the expected product (a).1... 

Intramolecular 2 + 2 + 2-cycloisomerizations of cyclic triynes and enediynes have been reported with RhCl(CO)(PPh3)2.126 The transition metal-catalysed rearrangement of alk-5-ynals to /-alkynyl ketones and cyclopent-l-enyl ketones was developed using [Rh(P(OPh)3)2]BF4 or Cu(OTf)2 as a catalyst and the effect of substituents on the partition to products was elaborated (Scheme 84).127... 

Quantum chemical studies of cyclizations of enediynes and enyneallenes have been reviewed.180 The intermediates are computationally tractable as a result of the unrestricted broken spin symmetry (UBS) approach using GGA functionals for the description of open-shell biradicals. The intermediacy of biradicals in Cope-type rearrangements, to which the Bergman and Myers-Saito reactions belong, are shown to be predictable using a very simple rule biradicals are likely to be intermediates if they are stabilized either by allyl resonance or by aromaticity. 

Carotene has been prepared by treating the a,a -dianion generated from starting sul-phone with bromine or iodine followed by rearrangement (equation 25). Utilizing the Ramberg-Backlund reaction, an interesting cyclic enediyne has been made (equation 26). ... 

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). ... 

Alcohols of general formula 27 may also be obtained by base-promoted [2,3] Wittig sigmatropic rearrangement. This method has been applied for the synthesis of 9-membered cyclic enediynes. ... 

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