Heptatrienes cyclization

Remembering that a typical endothermicity of very approximately 5 kJ mol 1 is found when there is no strain accompanying combination of two olefins to form a conjugated diene23,24, the cyclization reaction of (Z)-l,3,6-heptatriene, 137 (equation 43)... 

Our calculations showed that the first step, cyclization of the nitrene to an azabicyclo[4.1.0]heptatriene, is rate-determining. Our calculated barriers for cyclization of four fluorinated derivatives of lb are given in Table 6.87 The CASPT2/cc-pVDZ barrier of 13.4 kcal/mol for cyclization of 2,6-difluoro-phenylnitrene (10b) is 4.1 kcal/mol higher than the barrier computed for lb -+ 2b. In contrast, the calculated barriers to rearrangement of 3,5-difluoro-phenylnitrene (lOe) and 4-fluorophenylnitrene (10c) are very similar to that computed for unsubstituted phenylnitrene (lb). These computational results are consistent with the observed reluctance of pentafluorophenylnitrene (10a) and 2,6-difluorophenylnitrene (10b) to rearrange,48 1 81 83 and with the relative ease... 

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.

Limited thermochemical data are available for these two cyclization variants. Myers examined the thermolysis of (4Z)-l,2,4-heptatrien-6-yne (59) to give the diradical intermediate 61, which then abstracts hydrogen atoms from... 

The cyclization of enyne-allenes was first reported by Myers and coworkers in the late 1980s [34], These reactions are energetically favorable and often proceed at ambient temperature. The parent (Z)-l,2,4-heptatrien-6-yne (101) cyclizes to afford a,3-didehydrotoluene 98 with a half-life of 30 min at 75 °C (Fig. 9). 

The energy of activation for isomerization of norbornadiene itself is considerably largeThe reaction is mechanistically complex, and yields toluene and decomposition products as well as cycloheptatriene. Under the conditions used, part of the toluene is formed by isomerization of the cyclo-heptatriene , possibly via norcaradiene. In the gas phase the energy of activation for formation of cycloheptatriene from norbornadiene is about 51 kcal.mole and log is about 14.8 (refs. 24, 190). Activation parameters for the formation of toluene directly from norbornadiene in the gas phase are Ecf = 53 kcal.mole and log A — 14.2. These reactions probably involve initial cleavage of the C-1, C-7 bond in norbornadiene to yield an allylic diradical which can cyclize to norcaradiene (a precursor for both cycloheptatriene and toluene) as well as undergo other reactions. 

The nature of the transition state in the 3,3-shift was examined by Berson who found that (5 )-4-methyl-2-hepten-6-yne gave recovered starting material and both RZ)- and (5 )-4-methyl-l,2,5-heptatriene and the latter two gave (/ Z)-4-methyl-2-hepten-6-yne all reversibly with high stereospecificity prior to formation of cyclized and dimeric products (Scheme 7.51). These results are consistent with an allowed stereopathway via a chair-like transition state as opposed to a forbidden one or the one in which an effectively planar cyclohexene-1,4-diyl is involved. 

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. 

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. 

Like the Bergman cyclization transforming enediynes to aromatic systems, the Myers-Saito cyclization of (Z)-l,2,4-heptatrien-6-ynes also proceeds via the formation of 3-a-didehydrotoluene diradicals 3.428. But in contrast to the Bergman cyclization, the acyclic enyne-allenes 3.444-3.446 react along the Myers-Saito route under conditions close to physiological ones (Scheme 3.7) [221,222]. Cyclic enyne-allenes react in a similar manner to their acyclic counterparts. The biological activity of neocarzinostatin [24, 27] is attributed to this reaction. 

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