Addition of Carbenes to Alkenes

Methylene ( CH2) is the simplest of the carbenes uncharged, reactive intermediates that have a carbon atom with two bonds and two nonbonding electrons. Like borane (BH3), methylene is a potent electrophile because it has an unfilled octet. It adds to the electron-rich pi bond of an alkene to form a cyclopropane. 

Heating or photolysis of diazomethane gives nitrogen gas and methylene  

Two difficulties arise when using diazomethane to cyclopropanate double bonds. First, it is extremely toxic and explosive. A safer reagent would be more convenient for routine use. Second, methylene generated from diazomethane is so reactive that it inserts into C—H bonds as well as C=C bonds. In the reaction of propene with diazomethane-generated methylene, for example, several side products are formed. 

Show how the insertion of methylene into a bond of cyclohexene can produce the following, (a) 1-methylcyclohexene (b) 3-methylcyclohexene 

Two DuPont chemists discovered a reagent that converts alkenes to cyclopropanes in better yields than diazomethane, with fewer side reactions. The Simmons-Smith reaction, named in their honor, is one of the best ways of making cyclopropanes. 

In this and the following sections, we shall discuss the reactions of carbenes only on the basis of some typical examples. A comprehensive treatment would be the subject of a monograph devoted to carbenes only. 

The addition to alkenes is the most important reaction of carbenes first, because it is the simplest synthesis of cyclopropanes (particularly if carbenoids are used, see Sect. 8.7), and, second, it has been very well studied mechanistically. 

Experimentally, Doering and LaFlamme (1956) found, in the direct photolysis of diazomethane in (Z)-but-2-ene, a ratio of 46 1 of the cis- and 2-dimethyl- 

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates 

The main primary product of the thermolysis with ethene was cyclopropane, provided that the alkenes were present in large excess. The observed isomerization to propene was shown to be a consecutive reaction. Cvetanovic et al. (1967) also found products that indicate the formation of allyl radical intermediates leading, in multi-step reactions, to hexa-l,3-diene, pent-l-ene, and butane. The authors assumed that these compounds resulted from recombination of allyl and ethyl radicals. It is well known from combustion chemistry that the addition of methylene precursors to unsaturated hydrocarbons leads to higher hydrocarbons as precursors of soot (see e.g., Homann and Wellmann, 1983). 

---

Reactions involving free carbenes are very exothermic since two new theoretical treatment of the addition of singlet methylene to ethylene suggests that there is no activation barrier.168 The addition of carbenes to alkenes is an important method for synthesis of many types of cyclopropanes and several of the methods for carbene generation listed in Scheme 10.8 have been adapted for use in synthesis. Scheme 10.9, at the end of this section, gives a number of specific examples. 

This property is relatively rare in the very large number of reactions for which substituent effects were evaluated quantitatively106. It seems to be common, however, for all dediazoniations of arenediazonium ions and of related compounds, e.g. of substituted phenyl azides forming nitrenes, as well as for additions of carbenes to alkenes. 

Mechanism 8-8 Formation of Halohydrins 352 8-10 Catalytic Hydrogenation of Alkenes 355 8-11 Addition of Carbenes to Alkenes 358 8-12 Epoxidation of Alkenes 360... 

Addition of Water to Alkenes Oxymercuration 239 Addition of Water to Alkenes Hydroboration 242 Addition of Carbenes to Alkenes Cyclopropane Synthesis Reduction of Alkenes Hydrogenation 249... 

The formation of cyclopropanes by the addition of carbenes to alkenes was first reported by Doering and Hoffmann in 1954/ Since then, this most characteristic reaction of carbenes has been successfully exploited for the synthesis of cyclopropanes. The cyclopropane ring system is not only found as a structural element in a wide range of natural products, but is also a very useful synthetic intermediate leading to a variety of cyclic and acyclic compounds. ... 

Reactions of photochemically generated aryl carbenes with other species have also been studied. The mechanism of addition of carbenes to alkenes is of current interest. A non-concerted pathway with a reversible first step has been shown to be involved... 

A similar situation occurs in the addition of carbenes to alkenes to give cyclopropanes, another synthetically useful reaction shown in its simplest form in reaction (7.21). Figure 7.19(c) shows the movement of electrons for this reaction, which is similarly concerted but does not involve a cyclic transition state. 

With the ability to measure absolute rate constants, we are in a position to follow changes in as a function of reaction temperature, and thus to derive activation energies for the additions of carbenes to alkenes. Our first experiments involved PhCCl and the initial 4 alkenes of Table 7. [95] With trans-pentene and 1-butene, we found activation energies of 1 kcaFmol for the addition of PhCCl. Surprisingly, for tetramethylethylene and trimethylene, was negative (-1.7 and -0.8 kcal/mol, respectively). [95] In these cases, the observed rate of carbene to alkene addition increased as temperature decreased The preexponential (A) factors for the additions were low (2 x 10 - 6 x 10 M" s" ), indicating substantially negative activation entropies for these reactions. 

Addition reactions with alkenes to form cyclopropanes are the best-studied reactions of carbene intermediates, in terms of understanding carbene mechanisms and synthetic applications. Doering, in 1954, first reported the formation of cyclopropanes by the 1,2-addition of carbenes to alkenes. Singlet and triplet carbenes exhibit some important differences. Because it has an empty p orbital (like a carbocation) and a nonbonded pair of electrons (Hke a carbanion), the singlet carbene exhibits both carbocation and carbanion character. However, the triplet carbene behaves more as a diradical. These characteristics influence the types and stereochemistries of carbene reactions. A concerted mechanism is possible for singlet carbenes. As a result, the stereochemistry present in the alkene is retained in the cyclopropane. 

Figure S.7 Mechanism of stereospecific addition of carbene to alkene.

Table 16. Addition of carbenes to alkenes, cycloalkenes, allenes, and alken-ynes...

The sixth example in Table 6.6, carbene insertion into an adjacent C-H sigma (a) bond, is representative of the gas-phase reaction of carbenes. Indeed, since this intramolecular reaction effectively competes with the intermolecular addition of carbenes to alkenes seen earlier, the intermolecular process (Scheme 6.47) is best examined when no a-hydrogens are available in the carbene. 

Cyclopropanes can be formed by addition of carbenes to alkenes (Section 6.2.2.9)... 

FIGURE 10.41 Addition of carbenes to alkenes is a syn process with retention of stereochemistry. 

---