Bergman and Myers—Saito cyclizations

Scheme 1.3 Bergman and Myers-Saito cyclizations and DNA cleavage/damage.

FIGURE 30.1 The two quintessential cycloaromatization reactions, the Bergman and Myers-Saito cyclizations (top) and natural products that display biological activity based on these cyclizations (bottom). 

Scheme 1.2 Intermediate biradicals in the Bergman and Myers-Saito cyclization reactions.

ROUTES TO THE CYCLOAROMATIZATION OF ENEDIYNE AND ENYNE-ALLENE SYSTEMS. BERGMAN AND MYERS-SAITO CYCLIZATION... 

Like the case of Bergman and Myers-Saito cyclizations, the geometry of the transition state of the C -C (Schmittel) cyclization of enyne-allenes is close to the reaction product but its electronic state is close to... 

Polukhtine, A., Karpov, G., Pandithavidana, D.R., Kuzmin, A. and Popik, V.V. (2010) Photochemical triggering of the Bergman and Myers-Saito cyclizations. Australian Journal of Chemistry, 63(7), 1099-1107. 

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. 

This reaction is related to the Bergman Cyclization, Moore Cyclization, and Myers-Saito Cyclization. 

The most obvious effect on cycloaromatization, as the name implies, is the formation of an aromatic system. By delocalizing electrons in an aromatic ring, the product gains a high degree of stability, which is reflected in the small endothermicity of the Bergman cyclization and the exothermicity of the Myers-Saito cyclization. Since the Schmittel and Schreiner cyclizations are not true cycloaromatization reactions per se, they do not have the beneficial effect of the formation of an aromatic system and are therefore much are more endothermic than their counterparts. 

Unlike the other naturally occurring enediyne molecnles, neocarzinostatin chromophore (30) is activated into an enyne-butatriene. This unusual cumulene 57 undergoes a cyclization analogous to the Bergman cyclization, proposed concurrently by Myers and Saito. This cyclization, now referred to as Myers-Saito cyclization, produces the diradical 58 that can abstract hydrogen atoms from DNA. Thus, neocarzinostatin s bioactivity is remarkably similar to calichaemicin (Figure 4.14). 

Chen, W.-C., Zou, J.-W., Yu, C.-H. Density Functional Study of the Ring Effect on the Myers-Saito Cyclization and a Comparison with the Bergman Cyclization. J. Org. Chem. 2003, 68, 3663-3672. 

Like metal ions, which change activation barriers and affect the kinetics of Bergman cyclizations, the organometallic reagents also activate enediynes. It was noted above that the Myers-Saito cyclization occurs at a much lower temperature than the Bergman cyclization of enediynes... 

The study of Bergman, Myers-Saito and related biradical cyclizations using an unrestricted broken spin symmetry approach refined by single-point energy coupled-cluster calculations has been reviewed, and a simple rule outlined for predicting biradical involvement in such Cope-type rearrangements radicals were found to be probable... 

In an analogy to the relationship between Myers-Saito and Schmittel cyclization, Schreiner proposed another cyclization path of an endiyne, C, -Cj, as an alternative to the Cj-Cg Bergman cyclization (Figure 4.17). For the case where the terminal group is a hydrogen atom (38 40), the barrier is 27.1 kcal mol ... 

Stahl, F. Moran, D. Schleyer, P.V. Prall, M. Schreiner, P.R. Aromaticity of the Bergman, Myers-Saito, Schmittel, and directly related cyclizations of enediynes. J. Org. Chem. 2002, 67, 1453-1461. 

The photochemical cyclization of the Myers-Saito and Schmittel cyclization of enyne was described much later than the Bergman... 

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