Carbenes. Methylene. Cycloaddition

In its reactivity, iodomethylzinc iodide behaves as if it were a source of H2C , a species called methylene. It is not. Methylene belongs to a class of neutral molecules called carbenes, which contain a divalent carbon plus two unshared electrons that can be either paired or unpaired. A characteristic reaction of many carbenes is cycloaddition to double bonds to form cyclopropanes, a property that is shared by iodomethylzinc iodide. Free H2C is not involved in the Simmons-Smith reaction, but the similarity in behavior of iodomethylzinc iodide toward alkenes has led to referring to it and related compounds as carbenoids. 

The reaction of methyl acrylate and acrylonitrile with pentacarbonyl[(iV,iV -di-methylamino)methylene] chromium generates trisubstituted cyclopentanes through a formal [2S+2S+1C] cycloaddition reaction, where two molecules of the olefin and one molecule of the carbene complex have been incorporated into the structure of the cyclopentane [17b] (Scheme 73). The mechanism of this reaction implies a double insertion of two molecules of the olefin into the carbene complex followed by a reductive elimination. 

The earlier examples of [2 + 1] cycloaddition of a carbene (or carbenoid) on the double bond of alkylidenecyelopropanes to yield spiropentane derivatives were observed as undesired side reactions in the synthesis of alkylidenecyelopropanes through the addition of a carbene to a substituted allene [161]. In some cases the spiropentane derivative was obtained as the major product [161a, c] especially when a large excess of the carbene reagent was used. For example, when methyl 3,4-pentadienoate (610) was treated with a ten-fold excess of methylene iodide and zinc-copper couple the two products 611 and 612 were isolated in 1 4.5 ratio (Scheme 86) [161a]. 

Intermolecular enyne metathesis has recently been developed using ethylene gas as the alkene [20]. The plan is shown in Scheme 10. In this reaction,benzyli-dene carbene complex 52b, which is commercially available [16b], reacts with ethylene to give ruthenacyclobutane 73. This then converts into methylene ruthenium complex 57, which is the real catalyst in this reaction. It reacts with the alkyne intermolecularly to produce ruthenacyclobutene 74, which is converted into vinyl ruthenium carbene complex 75. It must react with ethylene, not with the alkyne, to produce ruthenacyclobutane 76 via [2+2] cycloaddition. Then it gives diene 72, and methylene ruthenium complex 57 would be regenerated. If the methylene ruthenium complex 57 reacts with ethylene, ruthenacyclobutane 77 would be formed. However, this process is a so-called non-productive process, and it returns to ethylene and 57. The reaction was carried out in CH2Cl2 un-... 

Cycloadditions onto Methylene- and Alkylidenecyclopropane Derivatives Table 48. Carbene additions to optically active methylenecyclopropanes... 

Hoffmann was the first to apply the concept of orbital symmetry to the cycloaddition of carbenes to olefins. This concept, which is based on EH-calculations was demonstrated for the [H-2]-cyclo-addition of triplet methylene to ethylene. 

Facile addition of either alcohols or amines to carbene complex 288 produces the / -am i n o-a, /i-unsaturated carbene complexes 289, which are useful for the preparation of cyclopentenone derivatives. Insertion of alkyne to 289 gives the 1,3-dienylcarbene complex 290, and its formal [3+2] cycloaddition gives cyclopentadiene 291. Under different conditions, [2+2+1] cycloaddition of vinylketene 292 produces the 5-methylene-2-cyclopentenone derivative 293 [88], The cyclopentenone 295, isomeric to 293, was obtained by the reaction of complex 294 with trimethylsilylacetylene, and oudenone (296) was synthesized by its hydrolysis [89]. 

In the above cycloaddition reactions, carbene is generated in situ. A more convenient way is to use Simmons-Smith reagent ", which transfers methylene from methylene iodide and zinc-copper couple to a carbon-carbon double bond (Scheme 2.56). In the reaction in Scheme 2.56, free carbene is not generated. The intermediate is believed to be ICH2ZnI, which behaves as an electrophile known as carbenoid. 

The reaction of alkenes with carbene gives cyclopropane as a major product by cycloaddition reactions but products in which methylene is inserted into the C-H single bond are also obtained. 

Many other 1,3-dipolar cycloadditions are known, amongst which is the addition of diazomethane (CH2N2). Expulsion of nitrogen from the adduct leads to the formation of a cyclopropane ring. Another way of achieving the same result involves the addition of a carbene such as the Simmons Smith reagent. This is generated from methylene iodide (CHjIj) and a zinc/copper couple. 

These examples show that the control of dichlorocarbene addition is hard to predict in the case of enones or dienones. The following example demonstrates that the regioselectivity of the carbene cycloaddition significantly increases if the starting polycyclic ketone is bridged by the ethylene rather than methylene chain, e.g. formation of 13, 14 and 15. ... 

Besides methylene and dihalocarbenes, carbonyl-substituted carbenes or their equivalents, particularly diazo esters, are the most important building blocks for the synthesis of cyclopropanes via [2 + 1] cycloadditions. This is because... 

Tebbe found that titanocene complexes promoted olefin metathesis in addition to carbonyl olefination. Despite the fact that these complexes have low activity, they proved to be excellent model systems. For example, the Tebbe complex exchanges methylene units with a labeled terminal methylene at a slow rate that can be easily monitored (Eq. 4.6) [54]. This exchange is the essential transformation of olefin metathesis. When reactions with olefins are performed in the presence of a Lewis base, the intermediate titanium metallacycle can be isolated and even structurally characterized (Eq. 4.7) [61] These derivatives were not only the first metathesis-active metallacyclobutane complexes ever isolated, but they were also the first metallacyclobutanes isolated from the cycloaddition of a metal-carbene complex with an olefin. These metallacycles participate in all the reactions expected of olefin metathesis catalysts, especially exchange with olefins... 

Periplanone B is the most active sex pheromone found in the alimentary tract and excreta of the American cockroach Periplaneta americana. An elegant total synthesis of this germacrane sesquiterpene was achieved by SCHREIBER and SANTINI Cyclodecatrienone 1 is an obvious precursor. One of the oxirane rings arises from epoxidation of the enone CC double bond, the other from [2-1-1]-cycloaddition of a carbene to the carbonyl bond of the enone. Oxidation of the methylene group introduces the additional carbonyl double bond. The CC double bond of the enone results from an elimination of HX in the a-X-substituted cyclodecadienone 2, which, on its part, is feasible by substitution of cyclodecadienone 3. An electrocyclic opening of the cyclobutene ring in 4 provides the 1,3-diene substructure in 3. 

The simplest cycloaddition, if the dimerization of two methylenes to form ethylene (Section 4.3) can be excluded, is the (l-f-2)-addition to ethylene of a singlet carbene CX2, where X is a halogen or another electronegative substituent. The reactions of methylene itself, and other carbenes that have triplet ground-states, will be deferred until the symmetry properties of electron spin are taken up. An incidental practical advantage of setting up the correlation digrams in Fig. 6.1... 

Very few Ni-allene complexes have been isolated and characterized, but many such species have been postulated as key intermediates in organic transformations catalyzed by Ni precursors. Notable examples of such applications include the cyclization of two arynes and one allene to give 10-methylene-9,l-dihydrophenanthrenes, " the one-pot coupling of allenes with aldehydes and silanes to give allyl silyl ethers, selective [3+2]-cyclization of allenes and Fischer carbenes, regio- and stereoselective, three-component assembly of allenes with aryl iodides and alkenyl-zirconium reagents, and regio- and chemoselective [2+2+2]-cycloaddition of electron-deficient diynes with allenes to polysubstituted benzene derivatives. ... 

Theoretical explorations of the formation of azines (38) from the addition of methylene- or dimethyl-carbene to their diazirine precursors have been reported. These reactions, which proceed through an ylide intermediate (39), show no enthalpy barriers, the activation energy being only a function of entropy factors. Dichlorocarbene has been shown to form ylides with diazines these ylides react further with dipolarophiles to give 1,3-dipolar cycloaddition products. ... 

Cycloadditions and insertions on tropone continue to be studied. A series of methylene insertions leads to intermediates from which the carbene (4) was... 

---