Bystander substituent effects

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

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... 

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. 

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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