Reaction of Carbenes in Solution

IV. Mechanisms of Reaction of Carbenes in Solution A. Excitation, Multiplicity and Reactivity... 

The chemistry of carbenes in solution hits been extensively studied over the past few decades.1-5 Although our understanding of their chemistry is often derived from product analyses, mechanistic details are often dependent on thermodynamic and kinetic data. Kinetic data can often be obtained either directly or indirectly from time-resolved spectroscopic methods however, thermochemical data is much less readily obtained. Reaction enthalpies are most commonly estimated from calculations, Benson group additivities,6 or other indirect methods. 

In this chapter, we describe how time-resolved photoacoustic calorimetry (PAC) can be used to obtain both the energetics and kinetics of carbenes in solution.7-9 PAC measures the magnitude and temporal profile of volume changes in solution following deposition of energy. These time-resolved volume changes can be directly related to carbene reaction enthalpies. We will first discuss the principles of this photoacoustic technique and then how it has been... 

In 1956, Doering et al. reported that methylene (CH2) inserted into the C H bonds of pentane, 2,3-dimethylbutane, and cyclohexene with no discrimination (other than statistical) between chemically different sites CH2 was classed as the most indiscriminate reagent known in organic chemistry. Doering and Kirmse also demonstrated that the C—H insertion reactions of CH2 in solution were direct, single barrier concerted processes with transition states that could be represented as 27 (Fig. 7.12). In particular, they did not proceed via initial H abstraction to give radical pair intermediates that subsequently recombined. (Triplet carbene C H insertions, however, do follow abstraction-recombination, radical pair mechanisms, as demonstrated in classic experiments of Closs and Closs and Roth (see Chapter 9 in this volume). 

As reactions of carbenes in organic glasses were discussed in this and other sections of this chapter we close this section with a short reference to a very interesting review of Tomioka (1994) of which we became aware when this chapter was already submitted to the publisher. Tomioka emphasizes strongly a caveat against extrapolations from solution results and from liquid phase mechanistic rules to matrix conditions. This can be shown, for example, in the stereospecificity of cyclopropanations of insertion products into the allylic CH bonds of alkenes. Studying Tomioka s review is clearly a must for all chemists who work with carbenes in a matrix ... 

Roth, H.D., Reaction of methylene in solutions. Selective abstraction reactions of CHj and CHj, /. Am. Chem. Soc., 93, 4935, 1971 Roth, H.D., Chemically induced nuclear spin polarization in the study of carbene reaction mechanisms, Acc. Chem. Res., 10, 85,1977. 

The reactions of carbenes, which are apparently unique in displaying electrophilic character in strongly basic solutions, include substitution, addition to multiple bonds, and co-ordination with lone pairs of electrons to form unstable ylides. This last reaction is of obvious relevance to a consideration of the reactions of heterocyclic compounds with carbenes and will be summarized. 

Using the pseudo-first-order equation A obsd = 0 + co2 [COiKwhere kcoi is the second-order rate constant for the reaction of carbene with CO2 and ko is the rate of carbene decay in the absence of CO2), solution-phase values of kcoi for phenylchlorocarbenes 9 and 12, and diphenylcarbenes 14 and 15 in dichloromethane were estimated (Table 4.1). (The concentration of CO2 in saturated dichloromethane solution at 25°C and 1 atm is 196mmol/L. ) The trend of these estimated second-order order rate constants agrees with that observed in low-temperature matrices by Sander and co-workers. ... 

Triplet-Intermediates from Diazo-Compounds (Carbenes) Table 7. Reactions of triplet-carbenes in solution... 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

It is not easy to explain why the triplet reactions that are energetically much less favored than those of the singlets become dominant at low temperature. Based on Ea and log A measured for triplet carbene abstraction (see Section 5.3), one can estimate the rate constant at 77 K to be <10 M s, suggesting that triplet carbene reactions in matrices at 77 K should not occur. Obviously, reactions of carbenes within matrices are controlled by factors that are not operating in solution phase, as one might expect from dramatic changes in reaction conditions. 

Carbenoid reactions are, of course, of considerable synthetic utility in organic chemistry, but consideration of this aspect is beyond the scope of the present work. While reactions in solution will be the major preoccupation, evidence from investigations of carbenes in the gas phase and in the solid state will also be included, although due caution must be exercised in translating conclusions from one phase to another. 

The interaction of [MN(SiMe3)2] (M = Li, Na, K) and LiTMP with carbenes (1) (R = i-Pr, R = Me), (3) (R = i-Pr) and (4) (R = Me) in solution was also reported. Evidence of complexation of these carbenes with the Li, Na, and K species in solution was given by the NMR shifts for the relevant carbene center. Recently, the reaction of carbene (1) with lithium l,2,4-tris(trimethylsilyl)cyclopentadienide was reported to result in monomeric carbene complexes with 1 1 stoichiometry (R = H R = f-Bu (6), adamantyl (7), or 2,4,6-trimethylphenyl(8)). The crystal structure of (6) showed that the cyclopentadienyl ring is coordinated in an -fashion to the lithium center (see Alkali Metals Organometallic Chemistry) and there is a single a-interaction present between the lithium and the carbene center (Li-C(carbene)... 

Consideration of the reactions outlined in Scheme 2 permits an estimate of AGjt for XA to be obtained. With the knowledge that triplet carbenes react irreversibly with Oj with a rate constant close to the diffusion limit can be expressed as the quotient shown in (24) where is the rate constant for reaction of XA in oxygen saturated solution, and is the rate constant in the absence of Oj. Since no significant difference in these rate constants can be detected, the estimate of is a limit set in part by the experimental uncertainty in k (Table 8). This value, 1 x 10" ... 

These generalizations about stereochemistry are not applicable to gas-phase reactions. The reason is that most simple carbene-alkene-addition processes are highly exothermic, since two bonds are formed and none is broken. The initial adduct may be formed with sufficient energy to undergo isomerization, resultiilg in loss of stereospecificity. In solution, the excess energy is dissipated very rapidly to the medium, and changes in stereochemistry do not usually occur after formation of the product. 

This section focuses solely on the use of a commercially available triazolin-5-ylidene carbene, viz. l,3,4-triphenyl-4,5-dihydro-l//-l,2,4-triazol-5-ylidene. When the stoichiometric reaction between this ligand and [RuCl2(/i-cymene)]2 was carried out in THF, a mixture of product and starting dimer was obtained. NMR analysis showed that coordination of the incoming carbene to the Ru center was accompanied by an orf/to-metaUation of the phenyl substituent in position 1, thereby releasing one equivalent of HCl in solution. Addition of a base (EtN/-Pr2 in excess) drove the reaction to completion and prevented side reactions between the protic acid and the highly reactive free carbene species. Thus, a single adduct could be obtained selectively and quantitatively (Eq. 

In pyridinium chloride ionic liquids and in l,2-dimethyl-3-hexylimida2olium chloride ([HMMIMjCl), where the C(2) position is protected by a methyl group, only [PdClJ was observed, whereas in [HMIMjCl, the EXAFS showed the formation of a bis-carbene complex. In the presence of triphenylphosphine, Pd-P coordination was observed in all ionic liquids except where the carbene complex was formed. During the Heck reaction, the formation of palladium was found to be quicker than in the absence of reagents. Overall, the EXAFS showed the presence of small palladium clusters of approximately 1 nm diameter formed in solution. 

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