Reactive Intermediate Chemistry

It is generally accepted that a singlet carbene undergoes a C H insertion (in a concerted manner) with a triangular transition state, while a triplet insertion favors a linear transition state in its abstraction of H. For example, in the reaction of 2-(o- methylenephenyl)bicyclo[2.2.1]heptane (40), insertion occurs predominantly into the exo-C H bond, giving the strained product (41, Scheme 9.9). This result indicates that the carbene (singlet) can approach the exo-C H bond from the side, but not from the endo side.64

Scheme 9.9

The difference in the TS between the singlet and triplet insertion becomes crucial in intramolecular processes, in which approach to a C H bond is restricted by ring strain. Photolysis of o-(n-butyl)phenydiazomethane gives fiveand sixmembered ring compounds as the major products, both of which are thought to originate from the singlet carbene.64 However, a similar reaction of optically active [2-(1-methylpropyl)oxy]phenylcarbene (43) affords a five-membered product (44) almost exclusively, but with the significant loss of enantiomeric purity ( 30% ee) (Scheme 9.10). This result is explained in terms of hydrogen abstraction by

Scheme 9.10

triplet followed by recombination of the radical pairs, rather than a concerted insertion from the singlet. Presumably, the concerted insertion reaction of the singlet involves the p orbital as well as the s orbital of the carbene. For the interaction of both orbitals with d-C H bonds, rotation must occur about the bond connecting the divalent carbon to the benzene ring, with concomitant loss of benzylic stabilization and deformation of bond angles. In contrast, transfer of the d hydrogen to the half-filled, in-plane s orbital of the triplet carbene can proceed by way of a favorable six-membered transition state in which the benzylic resonance is not disturbed.62

406 TRIPLET CARBENES

5.2. Chemically Induced Dynamic Nuclear Polarization

Chemically induced dynamic nuclear polarization (CIDNP)65 is a very powerful tool for establishing the existence of radical pair intermediates and their spin. CIDNP has reinforced the view that singlet carbene undergoes direct insertion into C H bonds and that the triplet abstracts hydrogen.

When radical pair reactions or reactions involving diradicals are carried out in the NMR probe, CIDNP produces strong emission and abnormally intense absorption signals in nuclear magnetic resonance (NMR) spectra. These abnormal signal intensities are associated with deviation from the Boltzmann distribution of the nuclear spin states. The spins of the nuclei attached to radical pairs or diradicals can promote or inhibit the probability of bond formation upon encounter because of their effect on the probability that these species will be in the singlet electronic spin state. The products of the radical pair or diradical reactions preserve the nuclear spins of their precursors long enough for the spin state population to be measured and recorded.

The radical pair theory of CIDNP depends on the assumption that only singlet radical pairs couple to give stable products. If a triplet pair is formed first, some will cross to singlets and couple before the pair correlation is lost by diffusion. If a singlet pair is formed initially, some will combine directly, some will be separated by diffusion, and some will cross to triplets, thereby increasing their prospects for diffusive separation. The electronic magnetic moments of the triplets will couple with the nuclear magnetic moments of nearby protons, producing complex magnetic quantum states. Those having the same symmetry as the singlet radical pairs will undergo the most rapid singlet–triplet transitions. Bond formation to produce a stable product leaves a nonequilibrium distribution of nuclear spin states in both the reaction product and the remaining radical pairs that may dissociate and react in other ways. As a result, the sense of nuclear polarization in products of combination of geminate radical pairs will depend on whether the pair was born as a singlet or a triplet.

The signs of net polarization ( ne þ for absorption and for emission) are given by ne ¼ me gAi according to the first-order treatment of Kaptein, where m, e, and Ai labels indicate the multiplicity of precursor ( for singlet precursor and þ for triplet precursor), the type of the product (þ for geminate products andfor scavenging products) and the sign of hyperfine coupling of the nuclei i under consideration, respectively. Based on the treatment, one can predict signs of polarization in NMR of the product derived from either the singlet or triplet radical pair (net absorption/A or emission/E for the net effect and EA:emission at the lower field and absorption in the higher field or AE for the multiple effect).66

Observation of emission and absorption in the NMR benzylic proton signal from an irradiated solution of diphenyldiazomethane in toluene was the first example showing the importance of the CIDNP technique.58 Triplet diphenylcarbene generated by photolysis of diphenyldiazomethane in toluene abstracts a hydrogen atom to generate the triplet radical pair, which either recombines to give 31, or diffuses apart, ultimately to produce dimers of each fragment (32, 33, Scheme 9.7,

408 TRIPLET CARBENES

No CIDNP signals from 47 are observed in the experiment in which polarized 48 is produced. This result indicates that while triplet methylene abstracts hydrogen, singlet carbene abstracts a chlorine atom.68 The reason why singlet abstracts chlorine atom is explained in terms of formation of an intermediate chloronium ylide (46). A similar singlet radical pair formation from singlet carbene is also shown in the reaction with ethers. Thermolysis of diazoacetate in benzyl ethyl ether gives C O insertion product (50). Strongly polarized signals due to the C O insertion product are observed in 1H and 13C NMR spectra and are explained in terms of a singlet radical pair. The formation of oxonium ylide (49) followed by homolysis of C O bond is proposed (Eq. 19). Again, no CIDNP is observed for the product derived from the same ylide by a nonradical mechanism, such as the Hoffmann type b-elimination of olefin.69

On the other hand, in the reaction of methylene with CCl4, a considerable fraction of Cl3CCH2Cl 1H NMR signals is found to be polarized both in direct and triplet-sensitized photolysis. It is deduced that both singlet and triplet methylene appear capable of abstracting chlorine atom from CCl4 (Eqs. 20 and 21).70

5.3. Laser Flash Photolysis Studies

The LFP techniques make it possible to observe directly the hydrogen atom abstraction process by triplet carbenes from appropriate H donors. The techniques also give useful kinetic information.

For example, LFP of diphenyldiazomethane in cyclohexane shows a strong absorption at 314 nm attributable to triplet diphenylcarbene (3DPC). As the 314-nm carbene signal decays, a new species showing a strong absorption band with lmax 334 nm (t ¼ 1ms) is formed. This band is attributable to the diphenylmethyl radical. The decay of triplet DPC at 314 nm kinetically correlates with the growth of the diphenylmethyl radical, indicating that the triplet DPC decays by abstracting a hydrogen atom from the solvent to generate the radical. The growth of the diphenylmethyl radical derived from DPC gives absolute rate constants for reaction of the carbene with cyclohexane (k ¼ 5:7 105 s 1).71

The observed rate constant (kobs) of a triplet carbene reaction is the sum of all decay rate constants of the triplet. These may include decay via an associated but

invisible singlet with which the triplet is in rapid equilibrium (see Eq. 10). Since the product studies indicate that radical-derived products are formed almost exclusively in this case, the growth rates reflect essentially pure triplet processes.

The monitoring techniques are used to obtain the absolute rate constants of DPC with other substrates (Q) known to react with triplet carbenes. The experiments are carried out at several reagent concentrations and the experimental pseudo-first- order rate constant, kobs, is plotted against the substrate concentration. It can be shown that kobs is expressed by Eq. 22

where kq is the rate constant of DPC with the substrate and ko includes all pseudo- first-order reactions DPC may undergo in any given solvent in the absence of substrates. A plot of the observed pseudo-first-order rate constant of the formation of the radical against [substrate] is linear, and the slope of this plot yields the absolute rate constant for the reaction of 3DPC with the substrate (Table 9.8).72 Kinetic isotope effects are determined to be 2.3 and 6.5 for cyclohexane and toluene, respectively.

The results reveal the nature of triplet DPC reaction in a quantitative manner. Thus, triplet DPC reacts with cyclohexane and THF at least 100 times as rapidly as does methyl or benzhydryl radical. Triplet DPC is 30 times less reactive with THF than is the phenyl radical. Thus, DPC has a reactivity toward hydrogen abstraction intermediate between those of methyl and phenyl radicals.

The activation parameters for hydrogen abstraction by DPC from diethyl ether and toluene have been measured (Ea ¼ 3:9 kcal/mol, A ¼ 107:8 M 1 s 1 and Ea ¼ 3:6 kcal/mol, A ¼ 107:2 M 1 s 1, respectively). The preexponential factors for reaction of triplet benzophenone with cyclohexane (108:66 M 1 s 1),73 tert-butoxy

radical with THF (108:7 M 1 s 1),74 tert-butyl radical with tri-n-butyltin hydride ð108:43 M 1 s 1Þ,75 and phenyl with tri-n-butyltin hydride (1010 M 1 s 1)76 are 1

to 3 orders of magnitude larger than those observed for reaction with DPC (14a) and DBC (18). These values are considerably smaller than expected on the basis of the corresponding data available in free radical hydrogen atom transfer

TABLE 9.8. Rate Constants (at 300 K) and Arrhenius Parameters for the Reaction of DPC (14a) with Various Hydrogen Donor Substrates

aCyclohexane ¼ c-C6H12, c-C6H10 ¼ cyclohexene, 1,4-CHD ¼ 1,4-Cyclohexadiene. bIn reciprocal seconds.

412 TRIPLET CARBENES

atom abstraction by DPC (14) from cyclohexane is examined.47 The results show carbene substitution has a minimal effect on the growth rate of the radical, which is in sharp contrast with that observed for the reaction with methanol, where the rate changes by a factor of 100 among the substituents studied (see Section 4.1). Only for the cases in which considerable delocalization into substituents is possible are the t values longer. This difference may represent enhanced stability of the triplet because of delocalization. These observations are in line with the radical nature of the triplet.

Behavior of FL (23) toward the C H bond is in contrast with that of DPC (14a). Picosecond LFP of diazofluorene (36) in cyclohexane generates a transient absorption band at 470 nm ascribable to FL. As time proceeds, a band at 497 nm appears, while the 470-nm absorption is still present. On a nanosecond time scale, the two bands at 470 and 497 nm are observed and assigned to 9-fluorenyl radical (FLH ) (t ¼ 1:4 ns), indicating that 23 rapidly abstracts a hydrogen atom (k ¼ 7:7 107 M 1 s 1) from cyclohexane to give FLH. Although the growth of the radical can be observed, product analysis indicates that triplet abstraction of hydrogen is a minor pathway in this case (see Section 5.1). Examination of the relative yields of 9-fluorenyl and 9-fluorenyl-9-d in neat cyclohexane and cyclohexane-d12 by measuring the absorbance change at 497 nm 100 ns after laser irradiation of 36, leads to a ratio of yields of 2. This value is too small to attribute to 3FL and is attributed to 1FL. The small S–T gap ( GST ¼ 1:9 kcal/mol) and high reactivity of FL allow singlet insertion reactions to predominate.52

Reaction of dimethoxyFL (23a), which is known to have a singlet ground state ( GST ¼ 2 kcal/mol), in cyclohexane supports this idea. These LFP studies in cyclohexane and cyclohexane-d12 indicate that a similar small kinetic isotope effect of 1.7 is observed for the decay of the transient absorption bands associated with 23a and the corresponding radical.53

Effects of the magnitude of GST on the hydrogen atom abstraction reactivity are seen more clearly in the reaction of cyclophane DPCs (20) with 1,4-cyclohexa- diene. Thus, kobs increases by a factor of 7 as the number of methylene units is decreased and GST decreases from 3 to 0.5 kcal/mol. This observation is interpreted in terms of some participation of the singlet for those carbenes with sufficient small energy gap.45

So, triplet carbenes are classified into two cases in terms of the behavior toward C H bonds depending on the magnitude of GST. One is exemplified by DPC and its derivatives in which there are triplet ground states with a rather large GST. Other carbenes in these groups are dibenzocycloheptadienylidene (18, GST ¼

5 kcal/mol), BA (22, GST >5:2 kcal/mol), and anthronylidene (52, GST ¼ 5:8 kcal/mol).

Fluorenylidene and its substituted derivatives are typical examples of the other class. Other carbenes showing similar behavior are monoarylcarbenes such as mononaphthylcarbenes (12) and phenyl(methoxycarbonyl)carbene (53, GST ¼

0:2 kcal/mol).

These observations suggested that the reactivity differences toward C H bonds are primarily due to changes in the S–T gap (and thus K) and only to a lesser extent

to a variation in triplet reactivity. However, this rough guide is not applicable for carbenes that are perturbed by conjugated p systems. For example, the reaction of XA (24, GST ¼ < 5 kcal/mol) with cyclohexane is sluggish and the C H insertion product is obtained only at elevated temperatures. This reaction is thermally activated and does not compete with other bimolecular reaction of 24 at room temperature. The absence of cross-product in the isotope tracer experiments (Scheme 9.8) shows that the insertion product is not formed by an encounter of free cyclohexyl radical with xanthenyl radical, indicating that the interaction of 24 with hydrocarbons appears to be primarily the result of a singlet rather than a triplet carbene. The reduced reactivity of 24 toward C H bonds is explained in terms of the reduced electrophilicity of this carbene.50

Conversely, triplet anthronylidene (52) abstracts a H atom from cyclohexane

with a rate comparable to that of FL, while GST of anthronylidene is much larger than that of FL.48,81 This finding is probably explained in terms of increased elec-

trophilicity of triplet anthronylidene as a result of a p delocalization of one of the unpaired electrons. Both IR and EPR spectroscopic studies of oxocyclohexadienylidene suggest an extensive delocalization of one unpaired electron. Moreover, halogenated oxocyclohexadienylidene derivatives are shown to undergo insertion into H2 and CH4 even at very low temperature (see Section 5.4.2).

5.4. Hydrogen Atom Tunneling85

5.4.1. Product Studies. Alkenes are known as diagnostic reagents for spin state of reacting carbenes. Thus, the reaction of a singlet carbene with an olefin usually results in the formation of a cyclopropane through stereospecific addition to the C C double bond, while a triplet carbene gives rise to a nonstereospecific addition product (see Section 7).

The experiments carried out by Moss and his associates >30 years ago, which triggered the research in this field and can be regarded as landmarks, reveal that reactions of arylcarbenes with solidified alkenes at 77 K are completely different from those expected based on well-established fluid solution-phase chemistry.

Photolysis of monophenyldiazomethane (54), for example, in cis-but-2-ene (55) solution at 0 C results in the formation of cis-1,2-dimethyl-3-phenylcyclopropanes (56) as syn and anti-mixtures along with small amounts of the trans isomer of the cyclopropane (57), and the C H insertion products, 3-benzylbut-1-ene (58) and 5- phenylpent-2-enes (59). Product distributions are changed dramatically when the irradiation is carried out in solidified butene at 77 K. Here the formal C H insertion products, that is, 58–59 are increased at the expense of the cyclopropane (56). The starting alkene configuration is retained (Scheme 9.11).86 Similar dramatic changes in the product distributions in going from liquid to solid are observed in the reaction of other arylcarbenes with other alkenes, although the extent of the change is somewhat sensitive to the structure of carbenes as well as alkenes.87

What is the cause of these dramatic changes? The formation of the cyclopropane (56) is reasonably explained in terms of stereospecific addition of singlet monophenylcarbene (55) generated by photolysis of the diazomethane (54), while the

Scheme 9.11

formation of the pentene [(Z )-59] can be interpreted as indicating that the singlet 1e undergoes insertion into the C H bonds of the methyl group of the butene. Alternatively, triplet states generated by the intersystem crossing of the singlet might abstract the allylic hydrogen from the butene, followed by recombination of the resulting radical pairs. The formation of 58 and (E)-59, on the other hand, is clearly understood in terms of the hydrogen abstraction–recombination (a–r) mechanism occuring in the triplet carbene. The appearance of these ‘‘radical’’ products in significant amounts suggests that the triplet states are responsible for the formation of the pentene (59).

This assignment is unambiguously supported by the labeling experiments. Thus, DPC (14) reacts with 13CH2 CMe2 at low temperatures to produce, in addition to the cyclopropane (60), 1,1-dimethyl-4,4-diphenylbut-1-ene (61) in which 13C3/13C1 label distributions are found to be 50:50 and 28:72 at 77 and 196 C, respectively (Scheme 9.12). The equal distribution of 13C between C1 and C3 at 77 C

Scheme 9.12

establishes an abstraction–recombination mechanism with complete equilibration of the radical pair. The results also eliminate the mechanism involving triplet carbene addition, followed by hydrogen migration for the formation of the butene (61), since such a mechanism would require an excess of 13C at C3.87b

A series of experiments using alkene matrices clearly suggests that in a rigid matrix at low temperatures, triplet states of arylcarbenes undergo abstraction of