Reactive Intermediate Chemistry

1. RELATIONSHIP BETWEEN STRUCTURE AND THE SINGLET–TRIPLET ENERGY GAP

Carbenes have two free electrons, and therefore can have two electronic states depending on the direction of spin of the electrons. There is a singlet state that has antiparallel spins and a triplet state that has parallel spins. Since the two electronic states have different electronic configurations, each state exhibits different reactivity and is affected differently by substituents. Generally speaking, the singlet state of the carbene undergoes concerted reactions with high efficiency leading to many useful products and, hence, has played an important role in synthetic organic chemistry. The triplet state, on the other hand, is a less reactive and selective reagent and, hence, is a less attractive intermediate from the standpoint of organic synthesis. Nonetheless, it has attracted much attention in materials science as a unit from which to construct organic ferromagnetic compounds.

In the reactions involving reactive intermediates, the most stable form usually plays a crucial role in controling the reaction pathway. However, in the reactions

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Throughout this chapter, T–S splittings and EST’s imply energy differences in the sense that ES ET. Thus, positive values indicate that the triplet is lower in energy than the singlet.

1.1.1. Electronic Effects. Because of more favorable overlap, the interaction of the carbon 2p orbital with substituent p or p orbitals is expected to dominate. The s (spn) orbital that lies in the nodal plane of the substituent p or p orbital will only interact with substituent s orbitals, and then only weakly. Thus its energy is mostly unperturbed by the substituent. A simple way to analyze the effect of the perturbation by substitution is to superimpose the orbitals of a prototypal carbene on those of the p system of the substituent.

Substituents interacting with a p system can be classified into three classes, namely, X: (p-electron donors such as NR2, OR, SR, F, Cl, Br, and I), Z (p-electron acceptors such as COR, SOR, SO2R, NO, and NO2), and C (conjugating groups such as alkenes, alkynes, or aryl).2

As shown in Figure 9.2(a), an X: substituent, which has a p orbital, or other suitable doubly occupied orbital that will interact with the p bond, raises the 2p orbital of the carbene, thereby increasing the separation of the 2p and spn (s) orbitals. The ground state of an X:-substituted carbene becomes a singlet, and many carbenes in this class are known. The most familiar of these are the halocarbenes.

The Z and C substituents having a p or p* orbital and evenly spaced p and p* orbitals, respectively, either lower the 2p–spn gap or leave it about the same, as shown in Figure 9.2(b and c). In either case, the ground state for these carbenes is expected to be T1 although the magnitude of EST may vary. It has been demonstrated by electron paramagnetic resonance (EPR) studies that most aryland diarylcarbenes have triplet ground states. From a valence bond viewpoint, it can be said that electron–donor groups stabilize the electrophilic singlet carbene

Figure 9.2. A carbene center interacting with (a) an X: substituent, (b) a Z substituent, and (c) a C substituent.

Figure 9.3. Change in the relative energy of singlet and triplet methylene with respect to <HCH at Becke 3LYP/TZ2P.

more than they do the radical-like triplet, while electron-withdrawing groups destabilize the singlet and lead to a greater EST.

1.1.2. Steric Effects. The magnitude of EST is expected to be sensitive to the carbene carbon bond angle. A linear carbene has two degenerate p orbitals, an arrangement that is calculated to provide the maximum value of EST. Bending the carbene removes the orbital degeneracy and reduces EST. As the carbene– carbon bond angle is contracted, the s orbital gains s character and consequently moves even lower in energy. The smaller the bond angle, the more energy it takes to promote an electron from the s to the p orbital, and the smaller EST becomes.

This effect is shown more quantitatively by calculations for methylene (Fig. 9.3).3,4 The calculations predict that the energy of singlet methylene will drop below that of the triplet state for carbenes with bond angles less than100 . On the other hand, theory also suggests that opening of the central angle strongly destabilizes the singlet state, but requires very little additional energy for the triplet, thus making EST larger.

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TABLE 9.1. DEST for Substituted Phenylcarbenes (PCs, 1)a

a B3LYP/6-311 þ G**//B3LYP/6-31G*. Single-point energy using the B3LYP/6-31G*-optimized geometry.

quantitative pictures (Table 9.1).5 For example, p-aminophenylcarbene (p-1a) is predicted to have EST of 0.7 kcal/mol, which is 4.7 kcal/mol smaller than that of parent PC (1e). On the other hand, p-nitrophenylcarbene (p-1k) is predicted to have a EST of 10.3 kcal/mol, 4.9 kcal/mol larger than that of 1e. A good correlation for EST is observed with sþp and the resultant slope (r) is 5.0. When the mesomeric effect of p donation is removed, as in the meta-substituted PCs, this effect is greatly attenuated. Similar correlation with sm is linear with a smaller r value of 3.3. The spin density at the carbene center does not depend on substitution, and therefore does not appear to contribute to the observed differential EST in these carbenes. Moreover, the charge on both the singlet and triplet carbenes gives a good correlation to sþp . The slope for this correlation is 0.03 for the singlet and 0.02 for the triplet, indicating that the singlet has slightly more charge separation than the triplet state does. Thus, the origin of this effect is preferential interaction of aryl substituents with the singlet rather than the triplet species. This difference is expected, as the singlet is conjugated to the p system via an empty p orbital, whereas the triplet presents only a singly occupied p orbital to the p system. In accord with this expectation, on phenyl substitution of methylene to form phenylcarbene, the carbene center gains 0.07 e in the singlet, while in the triplet, the C loses 0.02 e . Thus the phenyl stabilizes the singlet with respect to the triplet( EST decreases from 10 to 5 kcal/mol on going from CH2 to PhCH).

As expected, the angle about the carbene center in the singlet states (106.2– 106.6 ) is smaller than that in the triplet (134.1–134.8 ).

1.2.2. Hyperconjugation Effects. Singlet carbenes are isoelectronic with carbocations, and the same effects that stabilize carbocations will also stabilize singlet

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carbene (313) directly via the triplet diazo compound without first forming its singlet state. However, when the energy difference between the states is small, thermal reactivation and reaction from the upper state can compete with the reaction of the ground state. Thus, even though a carbene is formed in the triplet ground state, it may react predominantly from the singlet state, which has similar but higher energy.

Generally speaking, the rate of reaction in the singlet state (kS) is larger than that of the triplet (kT). The rate of singlet to triplet (kST) intersystem crossing and the reverse rate (kTS) are related to EST. Thus, kST > kTS if EST is large, but kST kTS when EST is less than 3 kcal/mol. In the latter case, singlet–triplet equilibration is usually assumed. The multiplicity that is involved in the reaction can be summarized as follows.

1.Carbenes with a singlet ground state far below the triplet react in the singlet state even if generated by triplet-sensitized photolysis.

2.Carbenes with a triplet ground state well separated from the singlet ( EST > 5 kcal/mol) react in a multiplicity determined by the method of generation.

3. Carbenes with a triplet ground state with a small energy separation ( EST < 3 kcal/mol) react in the singlet state regardless of the method of generation.

Of course, the rate constants (kS and kT) are dependent on the substrates and, hence, the above criteria should be taken only as a general guide. For example, if one chooses a quencher that efficiently reacts with the triplet state, such as O2, carbenes with triplet ground states react efficiently with the quencher to give products such as the corresponding ketones, regardless of EST values (see Section 6).

3. DIRECT OBSERVATION OF TRIPLET CARBENES

Carbenes are highly reactive species and, hence, their direct observation requires considerable effort. One way to observe them is to use the matrix isolation technique.12 In this technique, carbenes can be generated by irradiation of an appropriate precursor within a glass or more ordered inert gas matrix at very low temperature. The low temperature of the experiments stops or slows reactions of the carbene with the matrix materials. Also, the rigidity of the medium prevents diffusion and dimerization of the carbene. A second way to observe those highly reactive species is to conduct an experiment on a very short time scale.13 Such experiments rely on the rapid photochemical generation of the carbenes with a short pulse of light and the detection of the carbene with a probe beam. These pump–probe experiments can be performed on time scales ranging from picoto milliseconds. The low temperature and short time scale measurements support each other in the identification of the detected intermediates.