5-hexenyl radical clock

The rate constant for reduction of primary alkyl radicals with Sml2 has been determined using a radical clock (see Section 10.6) providing further information for understanding the mechanism [22]. The commonly used 5-hexenyl radical clock, where the rate constant for cyclisation is known (kc = 2.3 x 105 s-1 at 20°C), was used to determine the rate constant... 

Scheme 10.28 Use of the 5-hexenyl radical clock to determine Arrec n for primary alkyl radicals by Smb in a samarium Barbier reaction (Ar = p-methoxyphenyl).

A better-known example of a free radical clock is the 5-hexenyl radical. Timing is provided by the rearrangement reaction... 

Table II. Most of the data was obtained from radical clock studies. The neophyl radical rearrangement24 [Eq. (2)] was used for the majority of the kinetic data in Table II, but the ring expansion rearrangement reactions25-27 of radicals 7 and 8, cyclizations of 5-hexenyl type radicals,...

The kinetic data for these reactions are numerous, as shown in Table VI. Most of values were obtained by radical clock methods. The ring expansion of radical 7 has been employed as the clock in a study that provided much of the data in Table VI.74 Cyclizations of 5-hexenyl-type radicals also have been used as clocks,75-77 and other competition reactions have been used.78 Hydrogen atom abstraction from n-Bu3GeH by primary alkyl radicals containing a trimethylsilyl group in the a-, >8-, or y-position were obtained by the indirect method in competition with alkyl radical recombi-... 

The one-carbon ring expansion of (17) to (18) has been accurately measured and proposed as an alternative radical clock to the 5-hexenyl radical to help determine rates in the middle regions of the kinetic scale (Scheme 8). Ab initio calculations have indicated that the isomerization of the 3-oxocyclopentylmethyl radical to the 3-oxocyclohexyl radical is energetically more favourable than the process leading to the ring-opened 5-hexenoyl radical. " ... 

The kinetic data for the reaction of primary alkyl radicals (RCH2 ) with a variety of silanes are numerous and were obtained by applying the free-radical clock methodology. The term free-radical clock or timing device is used to describe a unimolecular radical reaction in a competitive study [2-4]. Three types of unimolecular reactions are used as clocks for the determination of rate constants for this class of reactions. The neophyl radical rearrangement (Reaction 3.1) has been used for the majority of the kinetic data, but the ring expansion rearrangement (Reaction 3.2) and the cyclization of 5-hexenyl radical (Reaction 3.3) have also been employed. 

Free radical clocks are reactions with known rate constants such as the cyclization of 5-hexenyl radicals (equation 76) or the ring opening of cyclo-propylmethyl radicals 46 (equation 74). Competition reactions of these processes compared to other reactions permit the assignment of rate constants to... 

The reaction of a citronellic ester enolate with electrophilic agents gives open-chain fluorinated products 32 and 33 only.11 The absence of rearranged fluorinated products in this system, a potential precursor to a 5-hexenyl-type radical clock, indicates that free radicals are not intermediates in the path to fluorinated products.12... 

Another common scenario in competition kinetics utilizes unimolecular radical reactions as a clock against which other reactions can be timed. Among the most commonly used free radical clocks are the cyclization of 1 -hexenyl and other radicals with double or triple bonds in the chain,33 ring opening,34 and p-elimination from alkoxyl radicals.35... 

The reaction of a citronellic enolate—a potential precursor to a 5-hexenyl-type radical clock—with various fluorinating agents leads exclusively to the corresponding a-fluorinated ester derivatives. The complete absence of cyclic fluorinated products is proof that the fluorination does not occur via radical intermediates, while the formation of a cyclic product in the reaction with xenon difluoride is an indication that electron transfer is a competitive process which does not give a fluorinated product31 (Scheme 9). 

Hexenyl radicals were used as radical clocks for the indirect measurement of the rate of reduction of radicals to anions using SmI2-HMPA. For example, reduction of primary iodide 4 using SmI2-HMPA resulted in the isolation of coupled product 9 in 20% yield and cyclised-coupled product 7 in 80% yield. As the rate of cyclisation of the intermediate primary hexenyl radical 6 was known, a rate constant of k= 106 M 1 s 1 could be estimated for the reduction... 

Radical clock rearrangements can be used to provide evidence for radical intermediates these include the ring opening of cyclopropylmethyl radical and the ring closing of the hexenyl radical (equation 21). 

The cyclization of 1-hexenyl radical as a clock reaction has been used in large number of cases, including hydrogen-atom abstraction from the phenolic group of a-tocopherol (vitamin E, EOH) [63]. The radicals were generated in the presence of EOH at 70 °C and the products, 1-hexene and methylcyclopentane, determined after the completion of the reaction. (See Eqs. 46-48.)... 

Because of the rather fast cyclization 131 - 132 (kj = 1 10s s"1 at 25 °C)90) this reaction or the cyclization of the related l-methyl-5-hexenyl radical 134 91) and the o-(3-butenyl)phenyl radical 135 92> is often used as a radical clock in reactions possibly passing through radical intermediates 93... 

The assumption that one radical is an appropriate model for another is most sound when one is using a clock to calibrate a bimolecular reaction and the local environment of the clock is similar to that of the radical of interest. For example, the rate constant found for reaction of the 5-hexenyl radical with a specific trapping agent should be a good approximation of the rate constant for reaction of another primary alkyl radical, especially one without substituents at C2. For most synthetic applications, the small errors in rate constants from this assumption will be unimportant. 

Limited examples of substituted alkyl radical clocks are available. Fortunately, some calibrated clocks that are available have rate constants in the middle ranges for radical reactions and should be useful in a number of applications. Examples of clocks based on the 5-exo cyclization of the 5-hexenyl radical are shown in Table 2. The data for the series of radicals 2-1 and 2-2 [17, 32, 34, 35] are from indirect studies, whereas the data for radicals 2-3 and 2-4 [3, 35-38] are from direct LFP studies. The striking feature in these values is the apparent absence of electronic effects on the kinetics as deduced from the consistent values found for secondary radicals in the series 2-1 and 2-3. The dramatic reduction in rate constants for the tertiary radical counterparts that contain the conjugating ester, amide and nitrile groups must, therefore, be due to steric effects. It is likely that these groups enforce planarity at the radical center, and the radicals suffer a considerable energy penalty for pyramidalization that would relieve steric compression in the transition states for cyclization. 

Strength) [24, 25]. There is a smaller rate difference between Cp/Cp with the more reactive 5-hexenyl radical radical clock methods have shown that the rate constant for H" transfer decreases by a factor of two from Cp(CO)3MoH to Cp (CO)3MoH at 298 K [30]. The considerable primary secondary tertiary selectivity of Cp (CO)3MoH in these radical clock studies (26 7 1) arises from steric interactions with the radical substituents [30]. 

The pioneering work on the calibration of intramolecular cy-clization of the 5-hexenyl radical by Ingold and co-workers provided the basis for the development of a large number of radical clocks." These are now used both for the calibration of rate constants for intermolecular radical reactions and as mechanistic probes to test for the intermediacy of radical intermediates in a variety of processes. Furthermore, the ready availability of bimolecular rate constants from competitive product studies using free radical clocks without the use of time-resolved experiments has greatly enhanced the synthetic utility of free radical chemistry. The same concept has recently been extended to radical ion chemistry. For example, rate constants for carbon—carbon bond cleavage reactions of a variety of radical cations and anions derived from substituted diarylethanes have been measured by direct time-resolved techniques. " ... 

Radical clocks are one experimental technique that has received considerable use in the analysis of radical reactions. Most radical clocks involve an intramolecular free radical rearrangement that proceeds with a well-defined rate constant. The prototype is the rearrangement of 5-hexenyl radical to cyclopentylmethyl radical, which occurs with a unimo-lecular rate constant of 1.0 X 10 s" at 25 °C (Eq. 8.75). The clock strategy is to embed a 5-hexenyl unit into the reactive system of interest. If a radical forms, and if its lifetime is comparable to or greater than 10 s, cyclopentylmethyl-derived products should form. 

Two new radical clocks have been calibrated, (notably the rearrangement of (5a) (6a) and (5b) (6b)). Rates were found to be 6.4 x 10 and 1.4 x F respectively. These two new clocks are intermediate between those of the neophyl and 1-hexenyl clocks and thus should be valuable new additions as tools to investigate reactions with intermediate rates (Scheme 3). ... 

In particular, allyl derivatives of Si, Ge, and Sn give aUylation efficiently [73-77], The corresponding 5-hexenyl derivatives have been used as radical clock in order to obtain some information about the timing of the steps [69,78],... 

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