Carbenes, 1,2-H shift

The second of our principal concerns is the contribution of quantum mechanical tunneling (QMT) to singlet carbene 1,2-H shifts and related reactions. There is strong evidence that QMT is important in the low temperature matrix reactions of (e.g.) t-buty 1 chlorocarbene (18)58 and benzylchlorocarbene (10a).59... 

The possible intervention of classical, competitive reactions in the low temperature solution chemistry of benzylchlorocarbene (10a) requires careful investigation. There are reasons to suspect azine (48) formation Goodman reported minor yields of azine in analogous MeCCl experiments,60 and Liu et al. found 40% of 48 in the photolysis of neat diazirine 9a.65 Perhaps azine formation is also significant at low temperature in hydrocarbon solvents. If so, the intervention of bimolecular azine formation, in competition with the unimolecular carbene 1,2-H shift, could lead to a nonlinear temperature dependence for the disappearance of 10a. Arrhenius curvature could then be explained without invoking QMT. 

With the intent to selectively derivatize CyD oligosaccharides,80 Abelt enlisted nitrogenous carbene precursors as labile guests.81 The involvement of supramolecular carbenes could be inferred based on intramolecular products stemming from 1,2-H shifts. Of course, 3//-diazirines that possess a-C-H bonds, like 3-methyl-3-phenyl-3//-diazirine (6) (Scheme 2), are susceptible to rearrangements in the excited state (RIES) that mimic the results of carbene 1,2-H shifts,82 e.g., 6 —>10 (Scheme 2). 

The related [1,2]-H shift in the isomeric triplet 1-phenylethylidene (53) was also investigated. The triplet carbene, generated from irradiation of the corresponding diazo compound, was characterized in low temperature inert matrices by EPR, IR, and UV/VIS spectroscopy. In this case, the carbene was stable in Ar up to the temperature limits of the matrix (36 K). Irradiation, however, readily converted the carbene to styrene. 

Singlet Carbene C-H Insertions Although [1,2]-H shifts are formally carbene C-H insertions, these rearrangements have different orbital symmetry aspects than those of intramolecular insertions. As described above, overwhelming evidence exists that triplet carbenes undergo abstraction-recombination reactions to... 

Now the 2-butenes comprise only 73% of the products, while 1-butene, a minor thermolytic product, increases to 23%. It is at least conceivable that some of the 1-butene here derives from an excited state of diazirine 8, rather than exclusively from carbene 6.3,15 Computational studies indicate that the 1,2-H shifts of 6 leading to the 2-butenes are preferred to the 1,2-H shift that yields 1-butene by a AAG of 2.6-3.3 kcal/mol. This again suggests that the substantial yield of 1-butene obtained from the photolysis of 8 is not simply derived from carbene 6.16... 

Additional evidence for a second intermediate in supposed carbene reactions comes from numerous studies.17-29 In the earliest experimental approach, the carbene precursor, frequently a diazirine, was photolyzed in the presence of increasing quantities of an alkene, which trapped the carbene with the formation of a cyclopropane (5 in Scheme 1). If carbene 2 were the sole product-forming intermediate, as depicted in Scheme 1, then the ratio of its alkene addition product (5) to its 1,2-H shift rearrangement product (4) would vary linearly with alkene concentration Eq. 9. 

Photolysis of diazirine 14 gave >90% of vinyl chloride, but, in accord with the observations of Tomioka, Liu, and Bonneau,17-20 photolyses in the presence of increasing quantities of TME led to a strongly curved correlation of addn/rearr vs. [TME]. And, carbene 15 was trapped by TME with, at most, 66% efficiency, so that about a third of the diazirine was converted to vinyl chloride by a 1,2-H shift that seemed to bypass the carbene. 

H shift more readily occurs with loss of nitrogen.22 Excited diazirines decay by fluorescence, carbene formation, or 1,2-H(D) migration coupled with N2 loss. C-D bonds are stronger than C-H bonds, so that deuteration retards the latter pathway and therefore RIES, leading to an increase in both fluorescence and carbene formation from 35-d6 22... 

The studies of MeCCl refocused attention on benzylchlorocarbene (10a). Earlier studies of 10a, over a temperature range of 0-31°C, afforded linear Arrhenius correlations for the 1,2-H shift, with Ea = 4.5-4.8 kcal/mol and log A 11.2 s-1.36 Additionally, LFP studies of p-CF3 and p-Cl substituted benzylchlorocarbenes (lOf and lOg) in isooctane over a temperature range of —3 to 47°C gave linear Arrhenius correlations with a (4.9 and 4.5 kcal/mol) and log A (10.9 s-1) values comparable to those found for parent carbene 10a.64... 

Of course carbene C-H insertion reactions are well known absolute kinetics have been reported for the insertions of ArCCl into isooctane, cyclohexane, and n-hexane,67 and of PhCCl into Si-H, Sn-H, and C-H bonds.68 More recently, detailed studies have appeared of PhCCl insertions into a variety of substrates bearing tertiary C-H bonds, especially adamantane derivatives.69 Nevertheless, because QMT is considered important in the low temperature solution reactions of MeCCl,60,63 and is almost certainly involved in the cryogenic matrix reactions of benzylchlorocarbene,59 its possible intervention in the low temperature solution reactions of the latter is a real possibility. We are therefore faced with two alternative explanations for the Arrhenius curvature exhibited by benzylchlorocarbene in solution at temperatures < 0°C either other classical reactions (besides 1,2-H shift) become competitive (e.g., solvent insertion, azine formation), or QMT becomes significant.7,59,66... 

In the same vein is the observation that the lifetime of dipropylcarbene (59) in CH2C12 or cyclohexane is 0.3 ns,84 which, after statistical correction is 48 times less than the lifetime ( 21 ns) of Me2C in pentane.22 This reflects promotion by the propyl bystander groups of 59 of the 1,2-H shift to Z- and E-3-heptene.84 (Dipropylcarbene can be photolytically generated from either an oxadiazoline (diazoalkane)84 or diazirine85 precursor, but RIES lowers the efficiency of carbene production in either case.) Recently reported LFP lifetimes for Et2C and MeCEt in cyclohexane or benzene are 0.6-3 ns (cyclohexane) or 1-5 ns (benzene),14 in accord with the lifetimes of S822 and S9.84 The rate constants for carbene disappearance in cyclohexane ( 3 x 108 to 2 x 109 s 1) are presumably limited by 1,2-H shifts.14... 

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... 

If the second substituent of an acetoxycarbene (or acyloxycarbene) can undergo a 1,2-H shift, then there may be an intracarbenic competition between this rearrangement and the expected 1,2-acetyl migration Eq. 28 provides an example where carbene 72 affords both 1,2-H and 1,2-Ac migrations. 

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... 

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... 

The simplest carbene capable of a 1,2-H shift, methylcarbene (78) is very difficult to study experimentally. Theoretical studies suggest that the carbene is a ground state triplet lying 5 kcal/mol below the singlet.97... 

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.)... 

In general, 1,2-C shifts do not compete effectively with the 1,2-H shifts of acyclic alkyl and alkylhalocarbenes. However, r-butylchlorocarbene (18) lacks the a-H needed for a 1,2-H shift, and so affords 1,3-CH insertion and 1,2-Me migration Eq. 14. Note that only for the thermally generated 18 is the 1,2-Me shift product (26) derived from the carbene. Photolytic generation of 18 from diazirine 24 gives only 1,3-CH insertion to dimethylchlorocyclopropane 25 in this case, the 1,2-Me shift product is formed by RIES of the diazirine.27 Based on the rate constant for the 1,3-CH insertion of t-BuCCl at 25°C (9.3 x 105 s 1), we can estimate A 105 s 1 for the 1,2-Me shift at 78°C. 

In contrast to the cyclopropyl- and cyclobutylhalo- (and acetoxy)carbenes, the cyclopentylhalo- and acetoxycarbenes (91), and their corresponding benzo derivatives, the indanylcarbenes (94), prefer 1,2-H shifts over 1,2-C shifts Eqs. 35 and 36.115 In the absence of strain relief to drive ring expansion, as with the cyclobutylcarbenes, 17, where kc exceeds ku, the 1,2-H shift is preferred.115... 

Carbene 103 undergoes 1,3-CH insertion to nortricyclene (105), but this reaction is either too rapid for LFP measurement by the pyridine ylide method (r <0.1 ns), or the insertion occurs by RIES of the precursor 2-norbomyldiazirine. Theoretically, a short lifetime is expected for 103 AG for the carbene insertion into the 6-endo-CU bond (103 — 105) is computed at 5.2 kcal/mol, about 6.7 kcal/mol less than the (unobserved) exo- 1,2-H shift to norbomene.16... 

In contrast, 1,2-H shift to olefin 106 is the dominant reaction of carbene 104, and this process is slow enough to be measured by LFP r = 300 ns in cyclohexane and 560 ns in pentane at 25°C.117 There is a polar solvent effect the lifetime decreases to 52 ns in acetonitrile. However, at least in the case of cyclohexane, the lifetime is solvent limited, with a KIE of 1.5 on the lifetime in cyclohexane- (460 ns). Carbene 104 is much longer-lived than dimethylcarbene (r 21 ns in pentane) or methylcarbene (<1 ns).22,89... 

A density functional study has been made of the competition between Wolff rearrangement and [1,2]-H shift in /S-oxy-a-diazocarbonyl compounds. Silver-catalysed decomposition of a-diazoketones (88 n = 0), derived from A-tosyl a-amino acids in methanol, gave rise to mixtures of products of Wolff rearrangement (89) and direct insertion of the carbene into the NH bond (90). The -amino acid derived species (88 n = 1) gave rise to products of Wolff rearrangement. 

Previous studies of the photochemistry of alkylchlorodiazirines have shown that the yield of trappable carbene is sensitive to the alkylcarbene structure. A laser flash photolysis study of phenanthridenes (91), precursors of alkylchlorocarbenes, in the presence of pyridine, has ruled out the intermediacy of a carbene-pyridine complex which partitions between pyridine-ylide formation and [1,2]-H shift. ... 

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