Myers-Saito cyclization reactions

Scheme 20.3 The Myers-Saito cyclization reaction of (Z)-l, 2,4-heptatrien-6-yne.

Thermolysis of 44 produced products derived from the Myers-Saito cyclization reaction. However, when 43 having a trimethylsilyl substituent at the acetylenic terminus was subjected to heating in the presence of 1,4-CHD at 70 °C for 3 h, the 1H-cyclobut[a]indene 46 was produced. A reaction mechanism involving an initial Schmittel cyclization to generate the benzofulvene biradical 45 followed by an intramolecular radical-radical coupling was proposed to account for the formation of the formal [2 + 2]-cycloaddition product 46. 

The benzannulated enyne-allenes 48 were likewise synthesized in situ from coupling between 41b and the bromoallene 47 (Scheme 20.11) [39]. Under the reaction conditions, 48 presumably underwent a spontaneous cation-mediated Myers-Saito cyclization reaction with a concomitant 1,2-shift of the trimethylsilyl group to give the naphthalene derivatives 49. 

Scheme 20.11 Cation-mediated Myers-Saito cyclization reaction.

The use of l-iodo-9-fluorenone (59) for cross-coupling with phenylacetylene produced 60, which on treatment with 51 gave the benzannulated enyne-allenes 61 (Scheme 20.14) [43], Thermolysis of 61 in 1,4-CHD at 75 °C promoted the Myers-Saito cyclization reaction, leading to 63 in excellent yields. Again, the benzylic radical center in 62 is a stabilized triarylmethyl radical. 

The diketone 64 was also readily prepared from 59 as outlined in Scheme 20.15. Condensation between 64 and 2 equiv. of 51b gave 65 in excellent yield. Thermolysis of 65 in 1,4-CHD at 75 °C also promoted the Myers-Saito cyclization reaction to generate the biradical 66. The aryl radical center in 66 was then captured by the allenic moiety to form 67, having two stabilized triarylmethyl radical centers. Subsequent hydrogen-atom abstractions from 1,4-CHD then furnished 68. 

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. 

The enyne-allenylphosphine oxides 120 and the benzannulated and naphthannu-lated analogs 121 and 122 having the diphenylphosphinyl group at the allenic terminus were readily prepared from the corresponding enediynyl propargylic alcohols 117,118 and 119 (Scheme 20.25) [64]. Without the unfavorable steric interactions, these conjugated derivatives smoothly underwent the Myers-Saito cyclization reaction. 

Fig. 104 Rhodium-catalyzed Myers-Saito cyclization reactions...

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 acetylene 27 became of interest since it undergoes a novel type of thermal cyclization reaction, later to be called the Myers or Myers-Saito cyclization (see Chapter 20 for a discussion of its relevance). The Z-diastereomer of 1,2,4-heptatrien-6-yne (27) was prepared by the sequence summarized in Scheme 5.33 [85]. 

The ability of (Z)-l,2,4-heptatrien-6-ynes (enyne-allenes) and the benzannulated derivatives to undergo cyclization reactions under mild thermal conditions to produce biradicals has been the main focus of their chemical reactivities [1-5]. With the development of many synthetic methods for these highly conjugated allenes, a variety of biradicals are readily accessible for subsequent chemical transformations. Cyclization of the enyne-allene 1 could occur either via the C2-C7 pathway (Myers-Saito cyclization) leading to the a,3-didehydrotoluene/naphthalene biradical 2 [6-10] or via the C2-C6 pathway (Schmittel cyclization) producing the fulvene/benzofulvene biradical 3 [11] (Scheme 20.1). 

The use of the zinc-copper couple to effect the reduction of the methanesulfonate 168 with rearrangement furnished 169 (Scheme 20.34) [10]. Treatment of 168 with methylmagnesium bromide in the presence of copper(I) cyanide to induce an SN2 -type reaction produced the methylated adduct 170. The half-life of the Myers-Saito cyclization of 169 is 66 h at 37 °C, whereas that of 170 is 100 min. The faster rate of cyclization for 170 has been attributed to a steric effect favoring the requisite s-cis or twisted s-cis conformation. 

Similarly, exposure of 180 to trifluoroacetic acid also promoted an internal SN2 displacement reaction to form 181 (Scheme 20.37) [68], The Myers-Saito cyclization generated the biradical 182 and, subsequently, 183. As in the case of 55, the benzylic radical center in 182 is a stabilized triarylmethyl radical. Several related transformations to produce enyne-allenes have also been reported [69, 70]. 

The Myers-Saito Cyclization is a similar reaction with a different substrate ... 

In the experimental thermolysis of 59, no Schmittel product was detected. Computational estimates for the activation enthalpy for the Schmittel cyclization of 59 range from 31 to 35 kcal mol , significantly higher than the barrier for the Myers-Saito cyclization of 20-22 kcal mol . Furthermore, the Schmittel cyclization is predicted to be endothermic (AH = -I-IO - -I-19 kcal mol ), while the Myers-Saito cyclization is exothermic. Therefore, the Myers-Saito cyclization of 59 is both theamodynamically and kinetically favored over the Schmittel reaction. 

Schmittel, M. Keller, M. Kiau, S. Strittmatter, M. A surprising switch from the Myers-Saito cyclization to a novel biradical cyclization in enyne-aUenes formal Diels-Alder and ene reactions with high synthetic potential, Chem. Eur. J. 1997, 3, 807-816. 

This reaction is related to the Myers-Saito Cyclization and Schmittel Cyclization. 

This reaction has been extended to azaenyne-allene cyclization, the so-called aza-Myers-Saito cyclization. ... 

This reaction, similar to the competing reaction of the Myers-Saito Cyclization, proceeds via a biradical intermediate, as supported by the trapping of a biradical intermediate with 1,4-cyclohexadiene and the experimental fact that the change of the polarity of solvent has no effect on the reaction rate and the ratio of products formed, indicating the absence of a zwitterionic intermediate. The proton abstraction by the vinyl radical leads to the formation of fulvene derivatives. An illustration of this reaction is provided here. 

Shortly after Finn s work came to light a catalytic rhodium(I) system was reported. An acyclic enediyne 40 was heated to 50 °C in the presence of just 0.05 equiv of RhCl(/-Pr2P)2 and EtjN in benzene to provide substituted arene 41 in 58% yield. The latter reaction is presumed to involve Myers-Saito cyclization of an in situ formed vinylidene complex. A catalytic cycle becomes possible due to steps involving /3-hydride elimination and reductive elimination. ... 

The Myers-Saito cyclization was first described independently in 1989 by Isao Saito (Kyoto University, Japan) and Andrew G. Myers (California Institute of Technology, Pasadena) whose findings were submitted for publication on June 7 and June 12, respectively. As a parallel transformation to the Moore cyclization (Chapter 4.12), in which an allenic fragment replaces the ketene moiety in the substrate, the Myers-Saito reaction provides a path to carbon diradicals. In its pioneering version, the reaction involved the cyclization of (Z)-l,2,4-heptatrien-6-yne (enyne-allene) 3, or its phosphine oxide derivative 5, to substituted a,3-dehydrotoluene diradicals, and subsequently to toluene derivatives 4 and 6. The reaction proceeds under thermal neutral conditions in 1,4-cyclohexadiene or other organic solvents such as methanol or carbon tetrachloride. 

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). 

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