Myers-Saito reactions

The prototype of this reaction is the Myers-Saito reaction, the rearrangement of eneyneallene (Z)-hepta-l,2,4-triene-6-yne (70) to a,3-didehydrotoluene (71). This C2—C7 cyclization yields a benzylic 7i-conjugated a,7t-biradical and is therefore... 

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. 

The switch from Myers-Saito to Schmittel cyclization occurs with phenyl or bulky groups attached to the alkynyl position of the enyne-allene. Engels compared the Myers-Saito and Schmittel cyclization for the parent reaction with R=H, phenyl, and f-butyl (Fignre 4.15) at B3LYP/6-31G. The activation enthalpy for the Myers-Saito reaction increases from 21.4 kcal mol" when R=H to 26.7 kcal mol" for R=phenyl, and 27.9 kcal mol for R=f-butyl. Conversely, the phenyl group decreases the activation enthalpy for the Schmittel reaction from 29.0 to... 

Nicolaou, K. C. Maligres, P. Shin, J. De Leon, E. Rideout, D. DNA-cleavage and antitumor activity of designed molecules with conjugated phosphine oxide-allene-ene-yne functionalities, J. Am. Chem. Soc. 1990,112, 7825-7826. Schmittel, M. Kiau, S. Strittmatter, M. Steric effects in enyne-aUene thermolyses switch from the Myers-Saito reaction to the —C -cyclization and DNA strand cleavage, Tetrahedron Lett. 1996, 37, 7691-7694. 

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. 

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... 

The Myers-Saito reaction of nonsubstituted enyne-allenes is kinet-ically and thermodynamically favored as compared to the Schmittel reaction while the concerted [4+2] cycloaddition is only 1.32 kcal/mol higher than the C -C cyclization and more exothermic (Ar = —69.38 kcal/mol). For the substituent = CH3 and Bu, the increasing barrier of the C -C cyclization is higher than that for the C -C cyclization because of the steric effect, so the increased barrier of the [4+2]... 

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). 

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. 

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 ... 

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

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