The Myers-Saito Cycloaromatization

Even in 1989 the mechanism of reactions concerning enyne-allene and cumulene-enyne bond systems, known as the Myers-Saito cycloaromatization, had been thoroughly investigated [3,17,18,267,268]. Thermal cycloaromatization of the enyne-allene 3.535 (Myers-Saito C -C ) to give naphthalene 3.536 competes with the Schmittel C -C enyne-allene cyclization to give indene 3.537 [18] (Scheme 3.34). Since the discovery of these cyclizations, they have been intensively studied, in particular. 

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. 

The benzannulated analog 115 was likewise synthesized from 114 (Scheme 20.24) [56, 63], However, unlike 109, thermolysis of 115 resulted in its slow decomposition without the formation of the cycloaromatized adduct 116. The lack of propensity for 115 to undergo the Myers-Saito cyclization reaction was attributed to unfavorable steric interactions between the diphenylphosphinyl group and the aryl ring of the benzannulated enyne-allene system, causing the allenic moiety to be rotated out of the plane defined by the aryl ring and preventing the cyclization reaction. 

Cumulene structures also undergo the Myers-Saito reaction. Cyclization of acyclic enyne[3]cumulenes, on the activation of Z-configured dienediyne 38 via acid solvolysis, has been described by Bruckner et al. It has been found that 38 dissolved in /-BuSH/dichloro-methane and treated with a catalytic amount of triflic acid forms the monocyclic cumulene 39. Storage of the mixture for 4 days at room temperature gave the corresponding styrene derivatives 40 and 41 these products form as a result of cycloaromatization via path A (benzoid radical). Independently, after... 

Other methods of forming six-mem bered rings include the Myers-Saito C -C cycloaromatization of enyne-allenes (Scheme 3.4) [25, 27, 29]. A possible pathway of enyne-allene 3.430 involves a,3-didehydrotoluene diradical 3.431. The acyclic enyne-allene 3.430 (Z-1,2,4-heptatrien-6-yne) undergoes the Myers-Saito cyclization at 37°C with ti/2 = 24 hours and at 75°C with tj/2 = 30 minutes to afford toluene [29]. The alternative Schmittel C -C cycloaromatization via diradical 3.432 is discussed in Section 3.3.3. 

Spontaneous cyclization of enediynes can occur as a click reaction via the formation of triazine ring. The cycloaromatization of a nonaryl enediyne occurs after its reaction with sodium azide. The azide 3.727 rearranges spontaneously to enyne-allene 3.728. The consecutive Myers-Saito cycloaromatization, involving diradical 3.729, leads to the heterocyclic product 3.730 (Scheme 3.83) [336]. Since the mechanism involves the formation of diradical 3.729 in ambient conditions, it can be used for the DNA cleavage. So, the enediyne 3.727 at 37°C for 4 hours cuts the single-stranded helix of a supercoiled DNA plasmid (pBR 322). 

The Bergman Cyclization (or Myers-Saito Cyclization) allows the construction of substituted arenes through the thermal or photochemical cycloaromatization of enediynes in the presence of a H donor such as 1,4-cyclohexadiene. 

An aza-variant of the cycloaromatization of propargyl azaeneynes, such as 50, via azaenyne-allenes 51, has been reported by Kerwin et al. The aza-Myers-Saito cyclization provides a,5-didehydro-3-picoline diradical 52, which affords either polar or radical-based trapping products 53 and 54, depending on the reaction solvent. The facility of the aza-Myers-Saito cyclization relative to the parent Myers-Saito cyclization was predicted based on DFT calculations these results also indicate that the corresponding C2-C6 (aza-Schmittel) cyclization, although disfavored in the case of 51, is... 

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). 

In 1995, Wang and Finn reported the ruthenium-mediated cycloaromatization of enediyne 32 into a naphthalene derivative 34, where the isolated ruthenium-vinylidene complex 33 was converted into 34 in a good yield (Scheme 21.12) [19], This process mimics Myers-Saito cyclization of 5-allene-3-en-l-yne via diradical... 

The thermal reaction of benzannelation of enediynes, the Bergman cycloaromatization, that occupies a special place, has been intensively studied [16]. These methods include also the less studied Myers-Saito [17] and Schmittel [18] cycloaromatization. Cycloaromatization of enediyne and enyne-allene blocks is described in books [19-23] and revietvs (Scheme 1.2) [24-30]. 

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

A series of thia enediynes have been recently prepared. The cycloaromatization was in this case promoted by an added base (EtsN). Moreover, the sulfone 56 was 1500-fold more reactive than the sulfoxide 55 and the sulfide was inert. These results indicate that in this case a different kind of cycloaromatization, the Saito-Myers reaction, is operating, as depicted in Scheme 19.14. This reaction is better illustrated in Section 19.5. 

---