Bystander substituents

The product ratio a /b (statistically corrected for the number of competing H migrants), gives the relative migration rate of Ha vs. Hb, or k /kub- The rate constant for the migration of Ha corresponds to the intrinsic migratory aptitude of Ha (M[H]) multiplied by the bystander assistance factor for Y, B[Y], The carbon atom that bears Hb has no bystander substituent, so that km, is simply A/[H], We thus obtain Eq. 24. 

The bystander substituent (Y) exerts a direct influence on the migrant group (M) at the migration origin. In contrast, a spectator substituent (X in Eq. 22)... 

A more detailed analysis of bystander substituent effects considers rearrangements in cyclic systems e.g., cyclohexylidene, 56.8... 

The lifetime of 15 (740 ns) was reduced to less than 10 ns by substitution of one or two Me groups on the methyl carbon atom i.e., the 1,2-H shifts of 61 and 62 were strongly promoted by methyl bystander substituents.60... 

The kinetics of alkylacetoxycarbene rearrangements provides another opportunity to observe the influence of bystander substituents on 1,2-H shifts. Carbenes 73-77 undergo the competitive rearrangements of Eq. 28 with the product distributions and associated LFP rate constants shown in Table 6 (with h and kAc partitioned according to the product distributions).88,92... 

Parallel substitution of a-Ph on 73 gives PhCHMeCOAc (75), where kH increases by 9.9 times while Ac increases only 1.3 times. Note that the a-Me bystander is 12 times (121/9.9) more effective than an a-Ph bystander substituent at driving the 1,2-H shift. A similar conclusion emerges upon comparison of the fcH values of 77 vs. 76, where an a-Me is substituted for an a-Ph group and increases by a factor of 12.92... 

Kinetic effects of solvent polarity are also observed with the alkylacetoxycarbenes. Polar solvents promote 1,2-H shifts,22 83 and the 1,2-H/1,2-Ac migration ratio of 76 increases from 50/50 to 95/5 as the solvent is changed from isooctane to TCE a parallel alteration (26/74 to 62/38) occurs with carbene 75.92 Thus, bystander substituents or a polar solvent exert positive effects on the... 

In Section VI.C, we saw that alkyl bystander substituents promoted 1,2-H shifts. In isooctane, Ah for Me2CHCCl and EtCCl (>108 s 1), as well as n-PrCCl (5.9 x 107 s 1) were increased by 1-2 orders of magnitude over Ah for MeCCl (3 x 106 s-1).86,87 Similarly, for PhCEt, which is formally derived from PhCMe by addition of a Me bystander substituent, AH is enhanced 60 times (to 3.6 x 108 s-1), while Ea is reduced by 2.5 kcal/mol by the methylation.83... 

Here we will briefly consider the kinetics and activation parameters of several representative intramolecular insertion reactions of carbenes, the role of bystander substituents, and the possible intervention of tunnehng. 

The inherent migratory aptitude of a group depends mainly on three factors (i) the intrinsic migratory aptitude, (ii) the bystander substituent on the migration origin, and (iii) the spectator substituent on the migration terminus. For reviews, see (a) Ref. 66a (b) Ref. 66d (see pp. 80-91)... 

We have seen that 1,2-H migrations in singlet carbenes may be affected by (e.g.) the participation of carbene precursor excited states, QMT, stabilization of the hydride shift transition state by polar solvents, and temperature. Here, we consider our third principal theme, the effect of substituents on the kinetics of carbenic rearrangements. We first examine the influence of bystander and spectator substituents (as defined in Eq. 22) on 1,2-H rearrangements of alkyl, alkylchloro, and alkylacetoxycarbenes. 

Using literature data, bystander assistance factors, B[Y], could be calculated for a number of substituents. For example, the thermolysis of certain ketone tosylhydrazone salts afforded dialkylcarbenes which gave competitive 1,2-H shifts, Eq. 23, where either Ha or Hb migrated. 

Both Af[H]s cancel, so that the bystander assistance factor, B[Y], for any substituent, Y, is simply the corrected product ratio a /b. 8 In Eqs. 23 and 24, bystanders Y were found to enhance H-shifts in the order MeO > alkyl > Ph quantitative data appear in Table 3.8... 

The intramolecular 1,2-H shifts of alkylchlorocarbenes are often very rapid making it difficult to relate structure with reactivity in terms of absolute rate constants. For example the ku values of Me2CHCCl, PhCHMeCCl, and EtCCl exceed 108 s 1 in hydrocarbon solvents at 25°C (Table 4).60 86 87 However, due to the stabilizing effect of the oxa spectator substituent, acetoxycarbenes react at much reduced rates relative to their chlorocarbene analogues,90,91 thus providing kinetically accessible results for a wide array of bystander-substituted alkylacetoxycarbenes.81 92... 

A single o- or p-methyl substituent has no influence on the rate of cyclization of the singlet tolylnitrene to the favored azirine. ° The methyl group has no bystander effect on benzazirine formation. Cyclization of 2,6-dimethylphenyl or 2,4,6-tri-methylphenylnitrenes necessarily proceeds toward a carbon bearing a substituent. A steric effect raises the barrier to cyclization by 1.5-2.0 kcal/mol, in excellent agreement with the predictions of Karney and Borden. The steric effect extends the lifetime of 2,6-dimethylphenylnitrene at ambient temperature to 13 ns in Freon-113 and of 2,4,6-trimethylphenylnitrene to 8 ns, in the same solvent (Table 11.4). ° ... 

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