Carbene-alkene addition reactions

Here the alkene and pyridine will compete for the carbene at a constant concentration of pyridine the observed pseudo first order rate constant for ylide formation will increase with increasing alkene concentration. A plot of kobs vs. [alkene] will be linear with a slope of kad, which is the rate constant for the carbene/alkene addition reaction affording cyclopropane 5 (Scheme 1). 

The second intermediate s identity has been debated since the mid-1980s. In 1984, Liu and Tomioka suggested that it was a carbene-alkenc complex (CAC).17 Similar complexes had been previously postulated to rationalize the negative activation energies observed in certain carbene-alkene addition reactions.11,30 A second intermediate is not limited to the CAC, however. In fact any other intermediate, in addition to the carbene, will satisfy the kinetic observations i.e., that a correlation of addn/rearr vs. [alkene] is curved, whereas the double reciprocal plot is linear.31 Proposed second intermediates include the CAC,17 an excited carbene,31 a diazo compound,23 or an excited diazirine.22,26 We will consider the last three proposals collectively below as rearrangements in the excited state (RIES). 

Philicity. A principal feature of the carbene-alkene addition reaction (Scheme 7.1) is the carbene s phihcity, that is the electronic character of its selectivity or response to the alkene s substituents. Early work of SkeU and Garner and Doering and Henderson showed that CBr2 and CCI2 preferentially... 

The data reveal a very large kinetic span for carbene-alkene addition reactions with k ranging from for additions of CeHsCCl or CeHsCF to... 

Eq. 4 enabled an empirical analysis of carbenic selectivity (or philicity). (1) It correlated the selectivities of many of the carbenes that had been studied up to 1976. [8,17] (2) It quantitated the qualitative concepts of carbene-aUcene addition reactions that were prevalent. (3) Most importantly, it could be used to estimate the selectivity of new carbenes. (4) It led to the identification of ambi-philic carbenes. (5) It would later be found to parallel conclusions drawn from ah intio electronic structure calculations of carbene-alkene addition reactions. Eet s examine features (1) - (4) ah initio calculational results will be considered below, in Section 2.1. 

It was clear that we needed a better theoretical Iramework to parallel and permit interpretation of carbenic philicity. Two crucial developments occurred around 1980 the application of ab initio computational methods and frontier molecular orbital (FMO) theory to carbene/alkene addition reactions, and the measurement of absolute rate constants for these reactions by laser flash photolysis (LFP). Together, these approaches greatly clarified our understanding of carbenic selectivity and philicity, and defined the current state of the art. ... 

Although we have restricted our discussions of carbenic philicity to carbene/ alkene addition reactions, the use of other substrates can also be informative. For example, both MeCOMe and (MeO)2C react with (oligomeric) methanol in pentane to give the formal 0-FI insertion products, 36 and 37, respectively. [72,73] As we would expect, the reaction of MeCOMe (7x10 M" s" ) is more rapid than that of (MeO)2C (2.5 x 10 M" s" ). Further study of the reactions of (MeO)2C with a wide range of hydroxylic substrates shows that log inversely proportional to the of ROFI, affording a Bronsted relation with a = -0.66. [107] Furthermore, from the absolute rate constants for (MeO)2C reactions with MeOH and MeOD, the primary kinetic isotope effect for the... 

From the point of view of both synthetic and mechanistic interest, much attention has been focused on the addition reaction between carbenes and alkenes to give cyclopropanes. Characterization of the reactivity of substituted carbenes in addition reactions has emphasized stereochemistry and selectivity. The reactivities of singlet and triplet states are expected to be different. The triplet state is a diradical, and would be expected to exhibit a selectivity similar to free radicals and other species with unpaired electrons. The singlet state, with its unfilled p orbital, should be electrophilic and exhibit reactivity patterns similar to other electrophiles. Moreover, a triplet addition... 

A wide-ranging experimental study of carbene-alkene addition activation parameters examined a series of substituted aryUialocarbenes (16) in reactions with (CH3)2C=C(CH3)2 and 1-hexene (Fig. 7.9). ... 

Moreno and coworkers published a study on the triplet carbene-ethene addition reaction. This process should involve two steps, namely the formation of a triplet trimethylene 1,3-diradical as an intermediate followed by intersystem crossing and formation of 1. The intermediate may live long enough to permit rotation at the CC bonds. In this way, the stereochemistry of the alkene will be lost and a non-stereospecific addition takes place. Moreno and coworkers calculated for the first step of the reaction C 2C i) H2C = CH2 a barrier of 11 kcalmol" and a reaction energy of -26 kcalmoF at the MP2/3-21G level. (It has to be mentioned in this connection that the 3-21G basis is far too small to lead to reliable energies in correlation calculations and therefore results are just of a qualitative nature ) Activation energies varied from 5 to 17 kcalmoF if CH2 was replaced by the triplet state of CH(CN), CH(BeH) and CHLi ... 

Of course, while Ken Houk, Karsten Krogh-Jespersen, and I were applying FMO theory to carbene/alkene additions, other investigators were also analyzing these reactions from a theoretical perspective. Here, we will briefly consider several of these reports. 

In 1976, Closs and Rabinow reported the use of flash photolysis to measure the rate eonstant for the addition of (triplet) diphenylcarbene (Ph2C) to butadiene in benzene at 25 °C k = 6.5x 10 M s". [88] This exciting result was the first condensed-phase carbene/alkene addition rate constant. However, the addition reactions of most singlet carbenes were expected to be significantly faster than that of bulky triplet Ph2C, too fast for the conventional flash lamp employed in Gloss s experiment with its p,sec light pulse. 

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. 

The predominant reaction mode of Cm is that of a strained, electron deficient alkene. Addition reactions typically occur in a 1,2 fashion across the 6-6 bonds, adding across the olefin and not opening up the basic Cm ring system. Representative of such reactions are the carbene addition and the Diels-Alder reaction shown in the first two examples of Figure... 

FIGURE 10.86 Stable three-membered rings can be formed in some alkene addition reactions. Two examples are epoxidation and carbene addition. 

A characteristic of transition states of the carbene-to-alkene addition reactions, particularly sensitive to the philicity of a carbene, is the angle of slope of the carbene plane relative to the double-bond plane. According to calculations [44, 45] one may hold that the carbenes for which in the transition states of addition to alkenes the angle a < 45° are electrophilic. The angle a > 50° is typical of nucleophilic carbenes, while the 45° < a < 50° region relates to the ambiphilic carbenes. Ab initio [44, 52, 53] and semiempirical (MNDO) [54] calculations of pathways of addition reactions of various carbenes have verified this dependence. 

Yet another kind of alkene addition is the reaction of a carbene with an alkene to yield a cyclopropane. A carbene, R2C , is a neutral molecule containing a divalent carbon with only six electrons in its valence shell. It is therefore highly reactive and is generated only as a reaction intermediate, rather than as an isolable molecule. Because they re electron-deficient, carbenes behave as electrophiles and react with nucieophiiic C=C bonds. The reaction occurs in a single step without intermediates. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

A common feature of these intermediates is that they are of high energy, compared to structures with completely filled valence shells. Their lifetimes are usually very short. Bond formation involving carbocations, carbenes, and radicals often occurs with low activation energies. This is particularly true for addition reactions with alkenes and other systems having it bonds. These reactions replace a tt bond with a ct bond and are usually exothermic. 

Absolute rates have been measured for some carbene reactions. The rate of addition of phenylchlorocarbene shows a small dependence on alkene substituents, but as expected for a very reactive species, the range of reactivity is quite narrow.119 The rates are comparable to moderately fast bimolecular addition reactions of radicals (see Part A, Table 11.3). 

The reactive intermediates under some conditions may be the carbenoid a-haloalkyllithium compounds or carbene-lithium halide complexes.158 In the case of the trichloromethyllithium to dichlorocarbene conversion, the equilibrium lies heavily to the side of trichloromethyllithium at — 100°C.159 The addition reaction with alkenes seems to involve dichlorocarbene, however, since the pattern of reactivity toward different alkenes is identical to that observed for the free carbene in the gas phase.160... 

Addition reactions with alkenes to form cyclopropanes are the most studied reactions of carbenes, both from the point of view of understanding mechanisms and for synthetic applications. A concerted mechanism is possible for singlet carbenes. As a result, the stereochemistry present in the alkene is retained in the cyclopropane. With triplet carbenes, an intermediate 1,3-diradical is involved. Closure to cyclopropane requires spin inversion. The rate of spin inversion is slow relative to rotation about single bonds, so mixtures of the two possible stereoisomers are obtained from either alkene stereoisomer. 

The addition of dichlorocarbene, generated from chloroform, to alkenes gives dichlorocyclopropanes. The procedures based on lithiated halogen compounds have been less generally used in synthesis. Section D of Scheme 10.9 gives a few examples of addition reactions of carbenes generated by a-elimination. 

Carbene protonation has been amply demonstrated by product studies, time-resolved spectroscopy, and kinetic measurements. The ability of singlet carbenes to accept a proton is not adequately described by the traditional scale of carbene philicities, which is based on addition reactions with alkenes. In particular, aryl- and diarylcarbenes excel as proton acceptors but would traditionally be classified as electrophiles. 

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. 

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