Intramolecular insertion pathway

As shown above, insertion of alkylidene carbenes is highly regioselective. However, when the normal 1,5-C-H insertion pathway is blocked, 1,4- or 1,6-C-H insertion takes place [Eq. (109)]. Thus, the cyclobutene 121 [192] and the six-membered enol ether 123 [193] were obtained in modest yields. Intramolecular insertion into carbon-carbon double bond provides a method for synthesis of cyclopenten-annulated dihydropyrrole 124, which results from homolytic scission of a methylenecyclopropane intermediate [194]. 

Experimental data are also consistent with a dissociative oxygen insertion pathway initiated by the dissociation of the anion PhCOO-, followed by coordination of 02, intramolecular hydrogen migration, and recoordination of PhCOO-. This mechanism has been ruled out on the basis of density functional calculations that placed the free energy of the intermediate for O2 insertion at about 120 kJ/mol above the energy of the corresponding intermediate in the reductive elimination mechanism. 

The suggested mechanistic pathway for this transformation implicates carbenoid 98 as a key intermediate, generated by a-elimination of the metallated oxirane. The highly reactive carbenoid undergoes intramolecular insertion rearrangement via either route A or B to yield dilithiated alkoxy enolate intermediates which, after usual workup, furnish the a,/3-unsaturated ketones, via H2O elimination <1995JA12700>. 

Direct observation of the carbonyl ylide (49) at 10 K in an argon matrix has also been reported the ylide is obtained by direct photolysis of (o-carbomethoxyphenyl)diazomethane (50) and undergoes reversible photoisomerization to the oxirane (51) as shown in Scheme 4. Competing intramolecular and intermolecular 0-H bond insertion pathways have been observed on analogous photochemically induced generation of [2-(hydroxymethyl)-... 

The pathways to compounds 2-12 probably require that in the first step the silylene 1 behaves towards MX as a nucleophile yielding an intermolecular donor-acceptor adduct B, followed by subsequent intramolecular insertion of either 1 into the M-X bond or X into the Si-M bond (Scheme 7), resulting in C. 

The proposed mechanism involves an acetoxy palladation of the triple bond in 133 to produce a vinyl-Pd(II) intermediate 135, which further undergoes an intramolecular insertion to give 136 (Figure 9.2). This is followed by insertion through carbo palladation with the formation of bicyclic intermediate 138, which is immediately oxidized by PhI(OAc)2 to give the Pd(IV) intermediate 139 (path a). Another pathway (path b) with the formation of intermediate 139 via 137 has also... 

Cyclopropanes are formed by the intramolecular insertion of a carbene into a C—H bond. A MINDO/2 study of the rearrangement of singlet ethylmethylene to propene and cyclopropane revealed that olefin formation (hydrogen migration) presents no energy barrier, but a critical energy of 1.4 kcal mol was found in the pathway to cyclopropane formation. ... 

The intramolecular insertion of a hydride into a coordinated olefin is a crucial step in olefin hydrogenation catalyzed by late transition metal complexes, such as those of iridium, rhodium, and ruthenium (Chapter 15), in hydroformylation reactions catalyzed by cobalt, rhodium, and platinum complexes (Chapter 16), and in many other reactions, including the initiation of some olefin polymerizations. The microscopic reverse, 3-hydride elimination, is the most common pathway for the decomposition of metal-alkyl complexes and is a mechanism for olefin isomerizations. 

Scheme 3 summarizes reaction pathways of 9-azidoacridine photolysis in different reaction conditions. The first photochemical step is the azide photodissoeiation in a singlet excited state with the formation of the singlet nitrene. Among the variety of the subsequent reaction pathways of aromatic singlet nitrenes, the following two main reactions can be mentioned [8] intramolecular insertion at the ortho position to form aziridine and then dehydroazepine and intersystem crossing to a triplet state, whieh is the ground state for nitrene. 

An initial step of orthometallation probably also occurs when aniline is allowed to react with ethylene in the presence of a rhodium(I) catalyst. 2-Methylquinoline (10 turnovers relative to the metal) and JV-ethylaniline (30 turnovers) are formed after 72 h in what are probably two independent reaction pathways (Scheme 144).216 It is interesting to note that the intramolecular cyclization step in the proposed216 mechanism (Scheme 144) has precedent in the palladium-promoted quinoline synthesis reported by Hegedus et al.16 (see Scheme 142), but the transformation 118->119 is unusual in the chemistry of organometallic insertion reactions.106... 

The overall mechanistic picture of these reactions is poorly understood, and it is conceivable that more than one pathway may be involved. It is generally considered that cycloheptatrienes are generated from an initially formed norcaradiene, as shown in Scheme 30. Equilibration between the cycloheptatriene and norcaradiene is quite facile and under acidic conditions the cycloheptatriene may readily rearrange to give a substitution product, presumably via a norcaradiene intermediate (Schemes 32 and 34). When alkylated products are directly formed from the intermolecular reaction of carbenoids with benzenes (Scheme 33 and equation 36) a norcaradiene considered as an intermediate alternatively, a mechanism may be related to an electrophilic substitution may be involved leading to a zwitterionic intermediate. A similar intermediate has been proposed143 in the intramolecular reactions of carbenoids with benzenes, which result in substitution products (equations 37-40). It has been reported,144 however, that a considerable kinetic deuterium isotope effect was observed in some of these systems. Unless the electrophilic attack is reversible, this would indicate that a C—H insertion mechanism is involved in the rate-determining step. 

Reactions of alkynyliodonium salts 119 with nucleophiles proceed via an addition-elimination mechanism involving alkylidenecarbenes 120 as key intermediates. Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne 121 due to the carbene rearrangement, or to a cyclic product 122 via intramolecular 1,5-carbene insertion (Scheme 50). Both of these reaction pathways have been widely utilized as a synthetic tool for the formation of new C-C bonds. In addition, the transition metal mediated cross-coupling reactions of alkynyliodonium salts are increasingly used in organic synthesis. 

On the basis of these results, a mechanism (Scheme 8.10) involving the intermediacy of a silver-carbene 54 was proposed in which the insertion product arises from the formation of the halonium ylide 55, followed by a 1,2 shift (55 —> 26, or 51 or 52). Alternatively, if the substrate and thus the halonium ylide 56 contain a (3-hydrogen, this could be removed by an intramolecular deprotonation with concomitant loss of halide resulting in formation of the olefin 57 and the a-haloacetate 53. At this stage, no independent evidence has been obtained to support this pathway thus this mechanism is purely speculative (see text below). Indeed, although the pathway has been depicted as involving metal-free intermediates, it is quite likely that this is not the case, but this awaits independent experimental verification. 

Most reactions of this category involve the base-induced generation of alkylidene-carbenes (R2C = C ) which undergo an intramolecular 1,5-carbon-hydrogen insertion providing a useful route for the construction of substituted cyclopentenes a competing intramolecular pathway is rearrangement to alkynes. 

Besides enyne metathesis [66] (see also the chapter Recent Advances in Alkenes Metathesis in this volume), which generally produces 1-vinylcyclo-alkenes, ruthenium-catalyzed enyne cycloisomerization can proceed by two major pathways via hydrometallation or a ruthenacycle intermediate. The RuClH(CO)(PPh3)3 complex catalyzed the cyclization of 1,5- and 1,6-enynes with an electron-withdrawing group on the alkene to give cyclized 1,3-dienes, dialkylidenecyclopentanes (for n=2), or alkylidenecyclopentenes (for n= 1) [69,70] (Eq. 51). Hydroruthenation of the alkyne can give two vinylruthenium complexes which can undergo intramolecular alkene insertion into the Ru-C bond. 

In conclusion, the [NiS] mediated formation of thioesters from alkyl, CO, and thiol groups lends support to an acetyl-CoA formation pathway that comprises CO insertion into a Ni Me and an intramolecular S -C bond formation between nickel-bound acyl groups and thiolate ligands. These reactions are favored at square-planar nickel complexes that enable two-electron redox reactions and readily add fifth ligands. 

---