Alkyl Radical Clocks

Some primary alkyl radical clocks are collected in Table 1. These examples demonstrate the wide range of kinetics that can be studied with radical clocks, but other classes of clocks are not nearly as well developed. Radical 1-1 was calibrated by kinetic ESR methods [2], and radical 1-9 was calibrated direetly by LFP [3]. All of the others [3, 17, 20-28] were calibrated by indirect methods. 

Most alkyl radical clocks with rate eonstants smaller than 1 x 10 s at ambient temperatures are ultimately calibrated against LFP-determined BuaSnH trapping kinetics [17, 29] this includes cases where the second-order competition studies were performed with tra-(trimethylsilyl)silane, (Me3Si)3SiH, because rate constants for alkyl radical reactions with the silane were determined via clocks that were eali-brated against tin hydride [30]. The rate constants for radical 1-10 depend on multiple methods, those for 1-11 depend on nitroxyl trapping kinetics, and those for 

1-12 and 1-13 depend on PhSH and PhSeH trapping kinetics. Rate constants for reactions of PhSH with alkyl radicals were determined by LFP [18], and these values were ineorporated into the kinetie values for PhSeH via clock studies [31]. A more recent calibration of PhSeH trapping kineties involved competition kinetic studies with a series of fast radieal clocks whose rate constants for cyclization were measured directly by LFP [3]. This work resulted in an adjustment of the PhSeH trapping kinetics and also those for reaction of PhSH with a primary alkyl radical, and, accordingly, the rate constants for the fast radical clocks must be adjusted. 

Arrhenius funetions for all of the reaetions shown in Table 1 have been determined or estimated, but those listed are for illustrative purposes and are among the more secure. The large log A values for ring openings of 1-11 and 1-13 and for rearrangement of 1-1 via initial 3-exo eyelization are typical for these types of re- 

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When the basis reaction in the competition kinetic scheme is a calibrated first-order rearrangement, a cyclization, ring opening, or rearrangement reaction, then the radical is called a radical Calibrated alkyl radical clocks that cover... 

Figure 5. Secondary and tertiary alkyl radical clocks and their rate constants for rearrangements at 20 °C in units of s ...

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. 

Lusztyk, J., MaiUard, B., Deyard, S., Lindsay, D. A., and Ingold, K. U., Kinetics for the reaction of a secondary alkyl radical with tri-n-butylgermanium hydride and calibration of a secondary alkyl radical clock reaction, /. Org. Chem., 52, 3509,1987. 

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 tertiary a-ester (26) and a-cyano (27) radicals react about an order of magnitude less rapidly with Bu3SnH than do tertiary alkyl radicals. On the basis of the results with secondary radicals 28-31, the kinetic effect is unlikely to be due to electronics. The radical clocks 26 and 27 also cyclize considerably less rapidly than a secondary radical counterpart (26 with R = H) or their tertiary alkyl radical analogue (i.e., 26 with R = X = CH3), and the slow cyclization rates for 26 and 27 were ascribed to an enforced planarity in ester- and cyano-substituted radicals that, in the case of tertiary species, results in a steric interaction in the transition states for cyclization.89 It is possible that a steric effect due to an enforced planar tertiary radical center also is involved in the kinetic effect on the tin hydride reaction rate constants. 

PRIMARY ALKYL RADICALS AND FREE-RADICAL CLOCK METHODOLOGY... 

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. 

The concept of this method is illustrated in Scheme 3.1, where the clock reaction (U R ) is the unimolecular radical rearrangement with a known rate constant ( r)- The rate constant for the H atom abstraction from RsSiH by a primary alkyl radical U can be obtained, provided that conditions are found in which the unrearranged radical U is partitioned between the two reaction channels, i.e., the reaction with RsSiH and the rearrangement to R. At the end of the reaction, the yields of unrearranged (UH) and rearranged (RH) products can be determined by GC or NMR analysis. Under pseudo-first-order conditions of silane concentration, the following relation holds UH/RH = (A H/A r)[R3SiH]. A number of reviews describe the radical clock approach in detail [3,4]. 

The biradical benzo-l,2 4,5-bis(l,3,2-dithiazolyl) (BBDTA) is known in the literature but characterization is incomplete. A new study reports the electronic, molecular, and solid-state structure of BBDTA.224 The lifetime of an alkyl phenylglyoxalate-derived 1,4-biradical has been estimated, using the cyclopropylmethyl radical clock , to be in the range 35—40 ns.225 The indanols (88) and their C(3) methyl and trideuteromethyl analogues have been prepared from phenyl benzyl ketone via photo-cyclization of an intermediate 1,5-biradical species.226,227 Selectivity for these products over their C(l) epimers is high but is profoundly effected by substitution in the benzyl ring or the alkyl side-chain. The findings are rationalized in terms of the conformational preference of the intermediate 1,5-biradicals. 

The elucidation of mechanisms of reactions of Sml2 have involved polarography, kinetics, radical clocks and trapping techniques (radical cyclisation) [19, 20]. The reagent is able to reduce alkyl halides and ketones/aldehydes, as shown in Scheme 10.25, in non-chain radical reactions. 

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 10.27 Use of a radical clock to determine the rate of reduction of alkyl radicals with Sml2.

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).

Xenon difluoride reacted with various carboxylic acids, and the type of transformation depends on the structure of the organic molecules35-39. The reaction with primary carboxylic acids involves free-radical intermediates. 6-Hexenoic acid was used as a free-radical clock device in which a A abs of 1.1 x 106 M-1s-1 at 25 °C was determined, while the alkyl radical was also spin-trapped to give an ESR signal37. The primary free radical was trapped by internal cyclization, and (fluoromethyl) cyclopentane in 25% yield was formed, while 6-fluoro-l-hexene could be formed from a radical or ionic intermediate, but 1-fluo-rocycloclohexane was not observed as a product (Scheme 42). 

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