Spectator substituents

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 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)... 

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... 

Spectator substituents, bonded to the carbene s migration terminus (Ci), directly influence the lifetime and philicity of the carbene, but they do not primarily alter the migratory aptitudes of migrants on C2. Oxa spectator substituents stabilize singlet carbenes by electron donation to the vacant carbenic p orbital (LUMO) cf. resonance hybrid 69. 

Nevertheless, acetoxycarbenes are less reactive than analogous chlorocarbenes, as shown by the data in Table 5, where we compare 1,2-H shift rate constants for phenoxymethyl-, cyclobutyl-, and isopropyl halo and acetoxy carbenes. Decreased rates of 1,2-H shifts are observed, due to the influence of the acetoxy spectator substituents, with the kinetic suppression reaching a factor > 900 for the comparison of cyclobutylacetoxycarbene with cyclobutylchlorocar-bene.81... 

Generation of 78 by thermolysis or photolysis of a diazoalkane or diazirine precursor, however, affords the singlet carbene, whose 1,2-H shift to ethene is opposed by a barrier of only 0.678 to 1.298 kcal/mol. Consequently, even in cryogenic matrices, singlet 78 rearranges more rapidly than it intersystem crosses to the triplet, which has therefore not been detected by UV or ESR in either an Ar matrix at 8 K or a Xe matrix at 15 K." The lifetime of singlet 78 at ambient temperature has been estimated at <0.5 ns.89,98b (Note the enormous spectator substituent effect of Cl the lifetime of MeCCl is 740 ns,60 at least 1500 times longer than that of MeCH.)... 

The kinetics of these rearrangements have been reviewed in detail 1 the most consistent measurements provide kc 1 x 106 s 1 for 55-C1, with 3 kcal/mol and log A ss 8 s 1 (AS —20 to —24 e.u.).109 The comparable data for 55-F are kc = 1.4 x 10s s-1, Ea = 4.2 kcal/mol, and log A = 8.3 s 1,1,96 Cy-clopropylfluorocarbene ring expands about 7 times more slowly than its chloro analogue. This difference, due to a slightly higher a ( 1 kcal/mol), reflects the larger spectator substituent stabilization by the better electron donor, fluorine. 

Pyridine ylide/LFP studies of 83-85 in pentane or isooctane afforded carbene lifetimes of 21-24 ns (k 4 to 5 x 107 s 1), similar to the lifetime of dimethylcarbene under these conditions. Unfortunately, these lifetimes are limited by reactions with the hydrocarbon solvents the lifetime of 83 is 1.5 times longer in cyclohexane-d12 than in cyclohexane. The observation that the lifetimes of 55-CI ( 1000 ns) and 55-F (—7000 ns) are considerably longer than those of 83 and 84 could reflect the superior stabilization provided by the halogen spectator substituents of 55, but this conclusion is tentative in the absence of definitive intramolecularly controlled lifetimes for 83-85. 

Other substituent, which does not participate in the stabilization, can be considered as a spectator substituent (Scheme 3) [34]. This stabilization system is particularly efficient with an amino group which is not only a 71-donating substituent but also a a-electron withdrawing group. This stabilization mode provides a large choice of substituents allowing an easy functionalization of the corresponding stable mono-aminocarbenes. In fact, several types of acyclic and cyclic amino carbenes have been already synthesized [8, 9]. 

Up to 2000, the number and variety of stable carbenes have been limited by the perceived necessity for two strongly interacting substituents. The preparation of stable or persistent (aryl)- or (alkyl)-(phosphino)carbenes as well as (aryl)(amino)-carbenes demonstrates that a single electron-active substituent allows the spectroscopic characterization of singlet carbenes under standard laboratory conditions. It has been shown that an amino substituent is more efficient than a phosphino substituent to stabilize a carbene center and that the steric bulk of the spectator substituent can be decreased even to the size of a methyl group in the phosphino series, so that a broad range of observable carbenes will be readily available. 

E2 eliminations as in Figure 4.26 usually proceed with anti- instead of. syn-selectivity. This is true although both eliminations benefit from transition states with 7t-like bonding interactions between the MOs of coplanar, breaking C-H- and C-X bonds (also cf. the discussion of Figure 4.20). The crucial factor is a steric effect that favors the anti- over the yyn-transition state, since the spectator substituents at C and adopt a nearly staggered structure in the anti-tran-... 

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)... 

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