Cyclometallation elimination

Very recently, Ma has reported a rhodium-catalyzed route to 18,19-norsteroid skeletons from bis-allenes, involving a cyclometallation-carbometallation-reductive elimination-Diels-Alder reaction cascade process.410... 

The current mechanistic understanding of these reductive cyclization processes is largely conjecture. Stepwise oxidative addition, migratory insertion, and reductive elimination (see Scheme 26) is a widely proposed mechanism. However, other mechanisms - such as initial cyclometallation - are to afford a rhodacyclopentadiene followed by either oxidative addition to a rhodium(v) intermediate or (perhaps more likely) bond metathesis with an additional molecule of silane (Scheme 28). 

A wide variety of five-membered zirconacydes 8 may be formed by the formal co-cycliza-tion of two 7i-components (3 and 6 alkene, alkyne, allene, imine, carbonyl, nitrile) on zir-conocene ( Cp2Zr ) (Scheme 3.2) [2,3,8]. The co-cydization takes place via the r 2-complex 5 of one of the components, which is usually formed by complexation of 3 with a zircono-cene equivalent (path a) ( Cp2Zr itself is probably too unstable to be a true intermediate) or by oxidation on the metal (cyclometallation/p-hydrogen elimination) (path b). Two additional routes to zirconocene r 2-complexes are by the reverse of the co-cyclization reaction (i. e. 8 reverting to 5 or 9 via 7), and by rearrangement of iminoacyl complexes (see Section... 

The proposed reaction mechanism is as follows (Scheme 16.83). Zinc metal reduces Ni(II) species to Ni(0). A nickelacyclopentadiene may be produced via coordination of two molecules of propiolates and regioselective head-to-head oxidative cyclometallation. Coordination and subsequent insertion of an allene into the Ni(II)-carbon bond give rise to a nickelacycloheptadiene intermediate. Finally, a benzene derivative is produced via reductive elimination followed by isomerization. 

Oxidative additions involving C-H bond breaking have recently been the topic of an extensive study, usually referred to as C-H activation the idea is that the M-H and M-hydrocarbyl bonds formed will be much more prone to functionalization than the unreactive C-H bond. Intramolecular oxidative additions of C-H bonds have been known for quite some time see Figure 2.15. This process is named orthometallation or cyclometallation. It occurs frequently in metal complexes, and is not restricted to "ortho" protons. It is referred to as cyclometallation and is often followed by elimination of HX, while the metal returns to its initial (lower) oxidation state. 

The overall reaction is best viewed as intramolecular oxidative addition of the C(l)—H bond to the Rh(I) center, causing cyclometalation (25), followed by reductive elimination of an enamine from the Rh(III) intermediate accompanied by allylic transposition. Notably, the allylamine ligand in the initial Rh(I) complex as well as the Rh(III) intermediate has an s-trans conformation with respect to the N—C(l) and C(2)—C(3) bonds, allowing the overall suprafacial 1,3-hydrogen shift to produce the is-configured enamine product. 

Attempts to prepare Ta(NEt2)5 by metathetic exchange reactions were found to lead to a complex in which activation of a )3-CH bond of an NEt2 ligand occurs with the elimination of diethylamine (equation 92), 244 345 Presumably steric pressure at the tantalum center promotes the cyclometallation reaction to generate the iminomethyl group. 

Synthetic routes to compounds containing M-C o bonds are fairly obvious. Substitution of, e.g., Cl by CH, can be effected by treatment with LiCH3 or CH3MgBr. A number of reaction types mentioned in Chapter 9 - oxidative addition, reductive elimination, insertion and cyclometallation (Sections 9.6 and 9.7) - have their uses in preparative routes to M-C bonds. The formation of organo-compounds of the lanthanides and actinides is an area of growing interest. Preparative methods are similar to those for other ER species where E is of relatively low electronegativity, e.g. ... 

In transition metal complexes of suitable geometry the metal may undergo intramolecular oxidative insertion into C-H bonds. Intermediates of Pd-catalyzed C-C bond formation can also undergo such cyclometalations to yield palladacycles . This can give rise to unexpected products or, if the palladacycles are too stable, the catalyst will be consumed and no further reaction will occur. At high temperatures reductive elimination from such complexes can occur to yield cyclic products. 

C-H transformation is achieved by cyclometallation by use of a unique catalytic system which involves the in-situ formation of a palladacycle [1]. Our work in this field takes advantage of the stability toward /3-hydrogen elimination of as,exo-aryl-norbomylpalladium complexes formed by a sequence of oxidative addition of an aryl halide to palladium(O) and stereoselective insertion of norbornene into the... 

Two closely related yet distinct pathways can be proposed for the arylation of C-H bonds based on coordination-directed C-H bond activation (1) cyclometalation with an MXn fragment followed by transmetalation with Ar-M and reductive elimination, or (2) cyclometalation with an ArMX fragment followed by reductive elimination (Scheme 1). Analogously, two catalytic cycles can be written for the current transformation. The first one would be Cycle 1 which proceeds via cyclo-palladation (with Pd(OAc)2) followed by transmetalation (Scheme 3). An alterna-... 

In the presence of Ni(dppe)Br2 the oxabicyclic alkenes 693 react with propynoic esters to yield 2H-benzo[ ]coumarins 696 (Scheme 172) <2001AGE1286>. The reaction mechanism involves cyclometallation of the propynoic ester and oxabicyclic alkene 693 to form the nickelacyclopentene intermediate 694. (3-Oxy elimination then forms the intermediate 695, which undergoes protonation and isomerization of the double bond followed by intramolecular lactonization to afford the desired 2/7-benzo[ ]coumarins 696 (Scheme 172) <2001AGE1286>. 

Recently An et al. disclosed a palladium(II)-catalyzed bis(peroxidation)/cycli-zation method for the synthesis of 3-(peroxymethyl)-3-peroxyoxindoles 209 from N - ar y 1 aery I a m i d e s 208 (Fig. 52) [235]. Using 5 mol% of Pd(OAc)2 in the presence of terf-butyl hydroperoxide, 46-96% of products 209 were obtained. The reactions were proposed to involve a Pd-catalyzed radical bis(peroxidation) of the acrylic unit [236] followed by a two-electron directed cyclometalation/reductive elimination reaction of intermediate bis(peroxide) 208A. 

Cyclometallation refers to a process in which unsaturated moieties form a metallacyclic compound. It is sometimes categorized under oxidative additions, but we prefer this separate listing. Examples of the process are presented in Fig. 4.31. Metal complexes which actually have displayed these reactions are M = L Ni for reaction a, M = Cp2Ti for reactions b and c, M = Ta for d, and M = (RO W for e. The latter examples involving metal-carbon multiple bonds, have only been observed for early transition metal complexes, the same ones mentioned under the a-elimination heading. 

The Murai reaction (Scheme 4), the replacement of an ortho-CH on an aromatic ketone by an alkyl group derived from a substrate olefin, is catalyzed by a variety of Ru complexes. This C bond formation occurs via chelate directed C-H bond activation (cyclometalation) in the first step, followed by alkene insertion into RuH and reductive elimination of the alkylated ketone. In a recent example of the use of a related cyclometalation in complex organic synthesis, Samos reports catalytic arylation (Suzuki reaction) and alkenylation (Heck reaction) of alkyl segments of a synthetic intermediate mediated by Pd(II). 

---